INS

Summary

INS (insulin, HGNC:6081) is a protein-coding gene on chromosome 11p15.5, encoding Insulin (P01308). Insulin decreases blood glucose concentration. It is a selective cancer dependency (DepMap: 12.1% of cell lines).

This gene encodes insulin, a peptide hormone that plays a vital role in the regulation of carbohydrate and lipid metabolism. After removal of the precursor signal peptide, proinsulin is post-translationally cleaved into three peptides: the B chain and A chain peptides, which are covalently linked via two disulfide bonds to form insulin, and C-peptide. Binding of insulin to the insulin receptor (INSR) stimulates glucose uptake. A multitude of mutant alleles with phenotypic effects have been identified, including insulin-dependent diabetes mellitus, permanent neonatal diabetes diabetes mellitus, maturity-onset diabetes of the young type 10 and hyperproinsulinemia. There is a read-through gene, INS-IGF2, which overlaps with this gene at the 5’ region and with the IGF2 gene at the 3’ region.

Source: NCBI Gene 3630 — RefSeq curated summary.

At a glance

• Gene–disease (curated): monogenic diabetes (Definitive, ClinGen) — +7 more curated relationships
• GWAS associations: 34
• Clinical variants (ClinVar): 163 total — 6 pathogenic, 16 likely-pathogenic
• Phenotypes (HPO): 65
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 12.1% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000207

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6081
Approved symbol	INS
Name	insulin
Location	11p15.5
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000254647
Ensembl biotype	protein_coding
OMIM	176730
Entrez	3630

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 non_stop_decay

ENST00000250971, ENST00000381330, ENST00000397262, ENST00000421783, ENST00000512523

RefSeq mRNA: 4 — MANE Select: NM_000207 NM_000207, NM_001185097, NM_001185098, NM_001291897

CCDS: CCDS7729

Canonical transcript exons

ENST00000381330 — 3 exons

Exon	Start	End
ENSE00001938789	2161168	2161209
ENSE00003494357	2160785	2160988
ENSE00003901829	2159779	2159997

Expression profiles

Bgee: expression breadth ubiquitous, 137 present calls, max score 100.00.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 9.1975 / max 5720.4061, expressed in 11 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118189	9.1975	11

Top tissues by expression

276 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	100.00	gold quality
islet of Langerhans	UBERON:0000006	99.96	gold quality
body of pancreas	UBERON:0001150	99.78	gold quality
pancreas	UBERON:0001264	99.05	gold quality
epithelial cell of pancreas	CL:0000083	80.80	gold quality
right lobe of liver	UBERON:0001114	64.33	gold quality
triceps brachii	UBERON:0001509	64.27	gold quality
gluteal muscle	UBERON:0002000	64.12	gold quality
right adrenal gland	UBERON:0001233	63.29	gold quality
left adrenal gland	UBERON:0001234	62.29	gold quality
olfactory bulb	UBERON:0002264	62.27	gold quality
tongue squamous epithelium	UBERON:0006919	61.07	gold quality
left adrenal gland cortex	UBERON:0035825	61.07	gold quality
right adrenal gland cortex	UBERON:0035827	60.43	gold quality
adrenal cortex	UBERON:0001235	59.95	gold quality
ectocervix	UBERON:0012249	59.63	gold quality
descending thoracic aorta	UBERON:0002345	59.02	gold quality
vastus lateralis	UBERON:0001379	58.39	gold quality
adrenal gland	UBERON:0002369	58.33	gold quality
oocyte	CL:0000023	58.03	gold quality
left uterine tube	UBERON:0001303	57.44	gold quality
quadriceps femoris	UBERON:0001377	57.41	gold quality
right coronary artery	UBERON:0001625	55.87	gold quality
lower esophagus mucosa	UBERON:0035834	55.80	gold quality
myocardium	UBERON:0002349	55.26	gold quality
endocervix	UBERON:0000458	54.73	gold quality
diaphragm	UBERON:0001103	54.62	gold quality
fundus of stomach	UBERON:0001160	54.26	gold quality
lateral nuclear group of thalamus	UBERON:0002736	54.02	gold quality
substantia nigra	UBERON:0002038	53.69	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	232623.63
E-MTAB-5061	yes	229022.13
E-HCAD-31	yes	116361.11
E-GEOD-81608	yes	49968.73
E-ENAD-27	yes	39279.18
E-GEOD-83139	yes	29426.29
E-MTAB-10137	no	101.71
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
COMT	Activation
HNRNPK	Repression
INSR	Activation
LPL	Activation
PPARG	Activation

Upstream regulators (CollecTRI, top): AIRE, ALX3, AP1, ATF2, ATF3, ATF4, ATF6, ATF6B, BHLHA15, BHLHE22, BHLHE23, BMAL1, CDX1, CDX2, CDX4, CEBPB, CEBPG, CLOCK, CREB1, CREBZF, CREM, DDIT3, DNMT1, EGR1, EPAS1, ESR1, FOS, FOXA2, FOXC1, FOXC2, FOXN1, FOXO1, FOXO3, FOXO4, GATA3, GLI1, GLIS3, GRHL3, GSX1, GSX2

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 12.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• crystal structure of Dab(A8)-insulin; although no more stable than native insulin, the non-standard analogue is twice as active: stability and affinity can therefore be uncoupled (PMID:11779231)
• evaluation of the relative contributions of existing obesity and a family history of obesity (FHOB) to blood pressure (BP) level, sympathetic activity, plasma leptin and insulin levels in young men without a family history of hypertension. (PMID:11800057)
• Chiral mutagenesis of insulin’s hidden receptor-binding surface: structure of an allo-isoleucine(A2) analogue (PMID:11866509)
• the cluster of CVD risk factors associated with Metbolic cardiovascular syndrome and intra-abdominal fat is present in obese prepubertal children and this situation seems to depend on the insulin basal level (PMID:11912547)
• hyperandrogenism and the insulin gene VNTR regulatory polymorphism are not associated in Spanish women (PMID:11937112)
• Relation between insulin-like growth factor-1 and insulin resistance in patients with acute stroke (PMID:11953210)
• results show that insulin functions as a bidirectional, condition-dependent regulator of hepatic cell Cp expression; the unique regulation of Cp may reflect its dual roles in inflammation and iron homeostasis (PMID:12029093)
• has a role in signaling through the malic enzyme and collagenase-1 AP-1 motifs. (PMID:12032154)
• Acid conditions increase the susceptibility of the molecule to conformational change and dissociation, and enhance the rate of fibrillation by providing a charged environment in which the attractive forces between the protein molecules is increased. (PMID:12051853)
• Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C amd (Ikappab-alpha) (PMID:12086926)
• insulin regulates both the association of glucokinase with secretory granules and the activity of the enzyme within the pancreatic beta-cell (PMID:12101177)
• The insulin gene VNTR polymorphism in Alzheimer’s disease. (PMID:12111440)
• The changes in plasma leptin, insulin and proinsulin levels in obese adolescents (PMID:12133430)
• Insulin at physiological concentrations enhances platelet fibrinogen binding in both Type 1 DM patients and healthy subjects, whilst C-peptide does not influence platelet activation. (PMID:12182905)
• The different energetic state of the intra A-chain/domain disulfide of insulin and insulin-like growth factor 1 is mainly controlled by their B-chain/domain. (PMID:12186542)
• Platelet reactivity in spontaneously diabetic rats is independent from blood glucose and insulin levels. (PMID:12189018)
• proinsulin increased with increasing insulin resistance and obesity in girls (PMID:12364457)
• hyperinsulinaemia could accelerate atherosclerosis by directly enhancing neutrophil transendothelial migration through increasing endothelial PECAM-1 expression via mitogen-activated protein kinase activation (PMID:12378388)
• insulin inhibits TNF-alpha-dependent cell killing, induction of p53, p21 and apoptosis in a human cervical carcinoma cell line (PMID:12392301)
• Structural analysis of insulin minisatellite alleles reveals unusually large differences in diversity between Africans and non-Africans (PMID:12404181)
• Modulates PC-1 processing and recruitment in cultured human cells. Stimulates PC-1 posttranslational processing and translocation to the plasma membrane, which in turn impairs insulin receptor signaling. (PMID:12441313)
• clinically relevant concentrations of insulin enhance platelet aggregability and leukocyte CD11b expression, but attenuate leukocyte respiratory burst activity (PMID:12479880)
• Obesity is associated with higher fasting insulin level, and fasting insulin is associated with C-reactive protein level, in healthy 2- to 3-year-old children (PMID:12529491)
• disproportionately elevated proinsulin levels in thalassemic patients indicate early beta-cell dysfunction due to siderosis (PMID:12589110)
• Polymorphism of the insulin gene is associated with increased prostate cancer risk (PMID:12610512)
• study demonstrates for the first time that insulin area under the curve and peak insulin measured in hyperinsulinemic states such as pregnancy correlate with testosterone levels (PMID:12620428)
• study of in vitro refolding of human proinsulin (PMID:12624089)
• Data show that in primary islet cells, unprocessed (mutant) proinsulin is sorted to the regulated pathway and then retained in secretory granules as efficiently as fully processed insulin. (PMID:12631734)
• Positive independent correlation of the CAG repeat number with body fat content, leptin and insulin. (PMID:12637980)
• A divergent INS protein in Caenorhabditis elegans structurally resembles this human protein and activates the human insulin receptor. (PMID:12654724)
• data demonstrate differential regulation of leptin secretion and pulsatility in adipocytes and synchronicity between leptin and growth hormone, cortisol, and insulin (PMID:12721156)
• Exercise training-induced increase in insulin sensitivity is not dependent on increase in adiponectinemia in healthy men. (PMID:12803245)
• Insulin may modulate Abeta42 levels acutely in humans. (PMID:12821730)
• 214 transcripts were similarly regulated by insulin and IGF-II through Insulin Receptor A, whereas 45 genes were differentially transcribed (PMID:12881524)
• structural analysis of 3-nitro-4-hydroxybenzoate and the Zn(II)-substituted R(6) insulin hexamer (PMID:12930990)
• Acute hyperinsulinemia impairs conduit vessel endothelial function independent of insulin sensitivity and lipid profile. Insulin may trigger endothelial dysfunction and promote atherosclerosis. (PMID:12946932)
• Essential for meal-induced plasma ghrelin suppression. Basal insulin availability sufficient for postprandial ghrelin suppression in type 1 diabetes(IDDM). Lack of meal-induced ghrelin suppression in nsulin deficiency in hyperphagia of uncontrolled IDDM. (PMID:14633852)
• INS VNTR can be considered a quantitative trait locus influencing glucose-stimulated insulin physiology in obese juveniles (PMID:14657411)
• the dominant effect of insulin is to act on the elongation portion of the fiber formation reaction (PMID:14659752)
• data are consistent with the hypotheses that insulin may negatively regulate ghrelin and that high-density lipoprotein may be a carrier particle for circulating ghrelin. (PMID:14671163)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	insb	ENSDARG00000034610
danio_rerio	ins	ENSDARG00000035350
mus_musculus	Ins2	ENSMUSG00000000215
mus_musculus	Ins1	ENSMUSG00000035804
rattus_norvegicus	Ins1	ENSRNOG00000012052
rattus_norvegicus	Ins2	ENSRNOG00000020405

Paralogs (2): IGF1 (ENSG00000017427), IGF2 (ENSG00000167244)

Protein

Protein identifiers

Insulin — P01308 (reviewed: P01308)

All UniProt accessions (4): A6XGL2, C9JNR5, I3WAC9, P01308

UniProt curated annotations — full annotation on UniProt →

Function. Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver.

Subunit / interactions. Heterodimer of a B chain and an A chain linked by two disulfide bonds.

Subcellular location. Secreted.

Tissue specificity. Expressed by pancreatic beta-cells (at protein level).

Disease relevance. Hyperproinsulinemia (HPRI) [MIM:616214] An autosomal dominant condition characterized by elevated levels of serum proinsulin-like material. The disease is caused by variants affecting the gene represented in this entry. Type 1 diabetes mellitus 2 (T1D2) [MIM:125852] A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. The disease is caused by variants affecting the gene represented in this entry. Diabetes mellitus, permanent neonatal, 4 (PNDM4) [MIM:618858] A form of permanent neonatal diabetes mellitus, a type of diabetes characterized by onset of persistent hyperglycemia within the first six months of life. Initial clinical manifestations include intrauterine growth retardation, hyperglycemia, glycosuria, osmotic polyuria, severe dehydration, and failure to thrive. PNDM4 transmission pattern is consistent with autosomal dominant or autosomal recessive inheritance. The disease is caused by variants affecting the gene represented in this entry. Maturity-onset diabetes of the young 10 (MODY10) [MIM:613370] A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the insulin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P01308-1	1	yes
F8WCM5-1	2, INS-IGF2

RefSeq proteins (4): NP_000198, NP_001172026, NP_001172027, NP_001278826 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004825	Insulin	Family
IPR016179	Insulin-like	Domain
IPR022352	Ins/IGF/rlx	Family
IPR022353	Insulin_CS	Conserved_site
IPR036438	Insulin-like_sf	Homologous_superfamily

Pfam: PF00049

UniProt features (48 total): sequence variant 27, helix 7, strand 4, disulfide bond 3, turn 3, peptide 2, signal peptide 1, propeptide 1

Structure

Experimental structures (PDB)

382 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
3W7Y	X-RAY DIFFRACTION	0.92
5E7W	X-RAY DIFFRACTION	0.95
5HQI	X-RAY DIFFRACTION	0.97
1MSO	X-RAY DIFFRACTION	1
3HYD	X-RAY DIFFRACTION	1
6VER	X-RAY DIFFRACTION	1.05
4FKA	X-RAY DIFFRACTION	1.08
3TT8	X-RAY DIFFRACTION	1.12
3W7Z	X-RAY DIFFRACTION	1.15
8OKY	X-RAY DIFFRACTION	1.17
5USP	X-RAY DIFFRACTION	1.17
5UOZ	X-RAY DIFFRACTION	1.17
5URT	X-RAY DIFFRACTION	1.18
1G7A	X-RAY DIFFRACTION	1.2
4AJX	X-RAY DIFFRACTION	1.2
7QGF	X-RAY DIFFRACTION	1.2
5UU2	X-RAY DIFFRACTION	1.22
7RKD	X-RAY DIFFRACTION	1.25
8PI4	X-RAY DIFFRACTION	1.25
6GV0	X-RAY DIFFRACTION	1.26
5HRQ	X-RAY DIFFRACTION	1.28
1G7B	X-RAY DIFFRACTION	1.3
3BXQ	X-RAY DIFFRACTION	1.3
5USV	X-RAY DIFFRACTION	1.3
9R4E	X-RAY DIFFRACTION	1.3
5UQA	X-RAY DIFFRACTION	1.31
5HPR	X-RAY DIFFRACTION	1.33
5UDP	X-RAY DIFFRACTION	1.35
3EXX	X-RAY DIFFRACTION	1.35
3FQ9	X-RAY DIFFRACTION	1.35

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P01308-F1	53.19	0.00

Antibody-complex structures (SAbDab): 13 — 3W11, 3W12, 3W13, 4OGA, 5CJO, 5WOB, 6B70, 6VEP, 6Z7W, 6Z7Y, 7KD6, 8ONI, 8ONK

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (3): 31–96, 43–109, 95–100

Function

Pathways and Gene Ontology

Reactome pathways

36 pathways

ID	Pathway
R-HSA-210745	Regulation of gene expression in beta cells
R-HSA-264876	Insulin processing
R-HSA-422085	Synthesis, secretion, and deacylation of Ghrelin
R-HSA-422356	Regulation of insulin secretion
R-HSA-6807878	COPI-mediated anterograde transport
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-74713	IRS activation
R-HSA-74749	Signal attenuation
R-HSA-74751	Insulin receptor signalling cascade
R-HSA-74752	Signaling by Insulin receptor
R-HSA-77387	Insulin receptor recycling
R-HSA-9615017	FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes
R-HSA-9768919	NPAS4 regulates expression of target genes
R-HSA-977225	Amyloid fiber formation
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-1266738	Developmental Biology
R-HSA-1430728	Metabolism
R-HSA-162582	Signal Transduction
R-HSA-163685	Integration of energy metabolism
R-HSA-186712	Regulation of beta-cell development
R-HSA-199418	Negative regulation of the PI3K/AKT network
R-HSA-199977	ER to Golgi Anterograde Transport
R-HSA-199991	Membrane Trafficking
R-HSA-212436	Generic Transcription Pathway
R-HSA-2980736	Peptide hormone metabolism
R-HSA-392499	Metabolism of proteins
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-5653656	Vesicle-mediated transport
R-HSA-597592	Post-translational protein modification
R-HSA-73857	RNA Polymerase II Transcription

MSigDB gene sets: 612 (showing top): GOBP_REGULATION_OF_RESPIRATORY_BURST, GOBP_POSITIVE_REGULATION_OF_MITOTIC_NUCLEAR_DIVISION, REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, GOBP_COGNITION, GOBP_POLYSACCHARIDE_BIOSYNTHETIC_PROCESS, GOBP_BEHAVIOR, GOBP_CIRCULATORY_SYSTEM_PROCESS, PID_HNF3B_PATHWAY, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_INFLAMMATORY_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS

GO Biological Process (61): positive regulation of cytokine production (GO:0001819), negative regulation of acute inflammatory response (GO:0002674), glucose metabolic process (GO:0006006), regulation of DNA-templated transcription (GO:0006355), acute-phase response (GO:0006953), G protein-coupled receptor signaling pathway (GO:0007186), cell-cell signaling (GO:0007267), positive regulation of cell population proliferation (GO:0008284), insulin receptor signaling pathway (GO:0008286), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), obsolete positive regulation of nitric oxide mediated signal transduction (GO:0010750), positive regulation of neuron projection development (GO:0010976), positive regulation of cell growth (GO:0030307), positive regulation of cell migration (GO:0030335), regulation of protein localization (GO:0032880), nitric oxide-cGMP-mediated signaling (GO:0038060), wound healing (GO:0042060), negative regulation of protein catabolic process (GO:0042177), vasodilation (GO:0042311), glucose homeostasis (GO:0042593), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), positive regulation of MAPK cascade (GO:0043410), positive regulation of cell differentiation (GO:0045597), negative regulation of gluconeogenesis (GO:0045721), positive regulation of glycogen biosynthetic process (GO:0045725), negative regulation of glycogen catabolic process (GO:0045818), positive regulation of glycolytic process (GO:0045821), positive regulation of mitotic nuclear division (GO:0045840), negative regulation of fatty acid metabolic process (GO:0045922), positive regulation of D-glucose import across plasma membrane (GO:0046326), positive regulation of insulin receptor signaling pathway (GO:0046628), alpha-beta T cell activation (GO:0046631), positive regulation of lipid biosynthetic process (GO:0046889), regulation of synaptic plasticity (GO:0048167), regulation of protein secretion (GO:0050708), negative regulation of protein secretion (GO:0050709), positive regulation of protein secretion (GO:0050714), cognition (GO:0050890), negative regulation of lipid catabolic process (GO:0050995)

GO Molecular Function (7): protease binding (GO:0002020), insulin receptor binding (GO:0005158), insulin-like growth factor receptor binding (GO:0005159), hormone activity (GO:0005179), identical protein binding (GO:0042802), receptor ligand activity (GO:0048018), protein binding (GO:0005515)

GO Cellular Component (9): Golgi membrane (GO:0000139), extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), Golgi lumen (GO:0005796), transport vesicle (GO:0030133), endosome lumen (GO:0031904), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), secretory granule lumen (GO:0034774)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Peptide hormone metabolism	2
Insulin receptor signalling cascade	2
Signaling by Insulin receptor	2
Regulation of beta-cell development	1
Integration of energy metabolism	1
ER to Golgi Anterograde Transport	1
Negative regulation of the PI3K/AKT network	1
Signaling by Receptor Tyrosine Kinases	1
FOXO-mediated transcription	1
Transcriptional Regulation by NPAS4	1
Metabolism of proteins	1
Intracellular signaling by second messengers	1
Metabolism	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of gene expression	3
signaling receptor binding	3
intracellular organelle lumen	3
acute inflammatory response	2
signal transduction	2
positive regulation of cellular process	2
gene expression	2
Golgi apparatus	2
bounding membrane of organelle	2
cytokine production	1
regulation of cytokine production	1
positive regulation of gene expression	1
positive regulation of multicellular organismal process	1
regulation of acute inflammatory response	1
negative regulation of inflammatory response	1
hexose metabolic process	1
DNA-templated transcription	1
regulation of RNA biosynthetic process	1
G protein-coupled receptor activity	1
cell communication	1
signaling	1
cell population proliferation	1
regulation of cell population proliferation	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to insulin stimulus	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
intracellular protein localization	1
regulation of localization	1
intracellular signaling cassette	1
response to wounding	1

Protein interactions and networks

STRING

11095 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
INS	ALB	P02768	999
INS	INSR	P06213	999
INS	IRS1	P35568	999
INS	IGF1	P01343	999
INS	IGF1R	P08069	999
INS	GCG	P01275	997
INS	IGFBP3	P17936	995
INS	IGFBP1	P08833	994
INS	IGFBP7	Q16270	990
INS	HSPB3	Q12988	990
INS	IGF2R	P11717	990
INS	NTRK1	P04629	989
INS	LEP	P41159	986
INS	IRS2	Q9Y4H2	986
INS	MB	P02144	985

IntAct

57 interactions, top by confidence:

A	B	Type	Score
INS	INS	psi-mi:“MI:0407”(direct interaction)	0.970
INS	INSR	psi-mi:“MI:0407”(direct interaction)	0.700
INSR	INS	psi-mi:“MI:0407”(direct interaction)	0.700
INSR	INS	psi-mi:“MI:0915”(physical association)	0.700
INS	IDE	psi-mi:“MI:0407”(direct interaction)	0.620
INS	IDE	psi-mi:“MI:0570”(protein cleavage)	0.620
INS	NOTCH2NLC	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (518): TCF4 (Two-hybrid), RGS20 (Two-hybrid), INS (Biochemical Activity), INS (Biochemical Activity), INS (Biochemical Activity), INS (Co-crystal Structure), INS (Affinity Capture-MS), INS (Affinity Capture-MS), INS (Protein-peptide), INS (Protein-peptide), INS (Two-hybrid), INS (Two-hybrid), INS (Two-hybrid), INS (Two-hybrid), NOTCH2NL (Two-hybrid)

ESM2 similar proteins: A2RRU4, A6QM06, B2RZ42, D3YZZ2, D4A2Q0, E7ERA6, F2Z333, O43612, O55232, O55241, O62827, O77668, P01308, P01356, P06307, P09535, P10764, P23362, P30406, P30407, P41155, P48645, P53366, P56717, P81264, P97260, Q02833, Q2T9U8, Q5BK01, Q5MNU5, Q6GQT6, Q6MG88, Q6UX46, Q6YK33, Q80UG6, Q86YD3, Q8BQB4, Q8CCB5, Q8WN12, Q969Z4

Diamond homologs: C0HJI1, C0HJI2, C0HJI3, C0HJI4, C0HJI5, C0HJI6, C0HJI7, C0HJI8, C0HJT9, C0HJU0, O73727, P01308, P01310, P01311, P01313, P01314, P01315, P01316, P01317, P01318, P01319, P01320, P01321, P01322, P01323, P01324, P01325, P01326, P01327, P01328, P01333, P01334, P01335, P01336, P01337, P01338, P01339, P01340, P01342, P04667

SIGNOR signaling

29 interactions.

A	Effect	B	Mechanism
INS	up-regulates	RHOQ
INS	up-regulates	PIK3CG
INS	down-regulates	GATA2
INS	down-regulates	DUSP6
INS	up-regulates	IGF1R	binding
INS	“up-regulates activity”	INSR	binding
INS	“down-regulates quantity by destabilization”	IRS1
INS	“up-regulates activity”	SLC2A4
INS	up-regulates	CEBPA
INS	“up-regulates quantity by expression”	LPL	“transcriptional regulation”
INS	“up-regulates activity”	LPL
INS	“up-regulates quantity by expression”	COMT	“transcriptional regulation”
INS	“down-regulates quantity by destabilization”	APOB
INS	“down-regulates activity”	FOXO
PDHX	“up-regulates quantity by expression”	INS	“transcriptional regulation”
CDX2	“up-regulates quantity by expression”	INS	“transcriptional regulation”
RAPGEF4	“up-regulates quantity”	INS	relocalization
calcium(2+)	“up-regulates quantity”	INS	relocalization
INS	down-regulates	GSK3B
INS	“down-regulates activity”	FOXO1
INS	up-regulates	TRIP10
INS	“up-regulates quantity by expression”	PPARG	“transcriptional regulation”
INS	up-regulates	CEBPB
INS	up-regulates	AKT1
PDX1	“up-regulates quantity by expression”	INS	“transcriptional regulation”
INS	up-regulates	AKT
INS	“down-regulates activity”	IRS1
IDE	“down-regulates quantity by destabilization”	INS	cleavage

Disease & clinical

Clinical variants and AI predictions

ClinVar

163 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	16
Uncertain significance	56
Likely benign	24
Benign	16

Top pathogenic / likely-pathogenic (22)

Variant ID	HGVS	Classification
13378	NM_000207.3(INS):c.143T>C (p.Phe48Ser)	Pathogenic
13382	NM_000207.3(INS):c.266G>T (p.Arg89Leu)	Pathogenic
13383	NM_000207.3(INS):c.266G>C (p.Arg89Pro)	Pathogenic
1457228	NC_000011.9:g.(?2181023)(2193087_?)del	Pathogenic
1459937	NC_000011.9:g.(?2181023)(2182533_?)del	Pathogenic
431443	NM_000207.3(INS):c.-152C>G	Pathogenic
1162205	NM_000207.3(INS):c.115C>T (p.Leu39Phe)	Likely pathogenic
1336487	NM_000207.3(INS):c.289A>C (p.Thr97Pro)	Likely pathogenic
1338622	NM_000207.3(INS):c.95G>T (p.Gly32Val)	Likely pathogenic
1338640	NM_000207.3(INS):c.103C>G (p.Leu35Val)	Likely pathogenic
1526009	NM_000207.3(INS):c.293G>T (p.Ser98Ile)	Likely pathogenic
1526010	NM_000207.3(INS):c.322T>G (p.Tyr108Asp)	Likely pathogenic
1526012	NM_000207.3(INS):c.101A>C (p.His34Pro)	Likely pathogenic
1526013	NM_000207.3(INS):c.103C>A (p.Leu35Met)	Likely pathogenic
1801850	NM_000207.3(INS):c.155C>G (p.Pro52Arg)	Likely pathogenic
2630345	NM_000207.3(INS):c.136C>T (p.Arg46Ter)	Likely pathogenic
2631502	NM_000207.3(INS):c.284G>A (p.Cys95Tyr)	Likely pathogenic
3393374	NM_000207.3(INS):c.283T>C (p.Cys95Arg)	Likely pathogenic
36401	NM_000207.3(INS):c.71C>T (p.Ala24Val)	Likely pathogenic
3773933	NM_000207.3(INS):c.129C>G (p.Cys43Trp)	Likely pathogenic
65581	NM_000207.3(INS):c.*59A>G	Likely pathogenic
916729	NM_000207.3(INS):c.174del (p.Glu59fs)	Likely pathogenic

SpliceAI

405 predictions. Top by Δscore:

Variant	Effect	Δscore
11:2160028:C:CT	acceptor_gain	0.9900
11:2160037:G:T	acceptor_gain	0.9900
11:2160040:G:T	acceptor_gain	0.9900
11:2160044:C:CT	acceptor_gain	0.9900
11:2160045:A:T	acceptor_gain	0.9900
11:2160783:AC:A	donor_gain	0.9900
11:2160784:CC:C	donor_gain	0.9900
11:2160028:C:T	acceptor_gain	0.9800
11:2160029:G:T	acceptor_gain	0.9800
11:2160036:C:CT	acceptor_gain	0.9800
11:2160039:C:CT	acceptor_gain	0.9800
11:2160034:A:T	acceptor_gain	0.9700
11:2160022:A:T	acceptor_gain	0.9600
11:2160008:G:C	acceptor_gain	0.9500
11:2160778:GGCTC:G	donor_loss	0.9500
11:2160779:GCTC:G	donor_loss	0.9500
11:2160779:GCTCA:G	donor_loss	0.9500
11:2160780:CTCAC:C	donor_loss	0.9500
11:2160781:TCA:T	donor_loss	0.9500
11:2160782:CA:C	donor_loss	0.9500
11:2160783:A:AG	donor_loss	0.9500
11:2160783:A:C	donor_loss	0.9500
11:2160784:C:A	donor_loss	0.9500
11:2161088:C:CA	donor_gain	0.9500
11:2160012:C:CT	acceptor_gain	0.9400
11:2160021:C:CT	acceptor_gain	0.9400
11:2160783:A:AC	donor_gain	0.9400
11:2160784:C:CC	donor_gain	0.9400
11:2160033:C:CT	acceptor_gain	0.9300
11:2160052:C:CT	acceptor_gain	0.9300

AlphaMissense

687 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:2159858:G:C	C109W	0.999
11:2159859:C:A	C109F	0.999
11:2159859:C:T	C109Y	0.999
11:2159862:T:C	Y108C	0.999
11:2159859:C:G	C109S	0.998
11:2159860:A:T	C109S	0.998
11:2159885:G:C	C100W	0.998
11:2159886:C:G	C100S	0.998
11:2159886:C:T	C100Y	0.998
11:2159887:A:G	C100R	0.998
11:2159887:A:T	C100S	0.998
11:2159898:C:T	C96Y	0.998
11:2159900:G:C	C95W	0.998
11:2159901:C:G	C95S	0.998
11:2159902:A:T	C95S	0.998
11:2159871:A:G	L105P	0.997
11:2159886:C:A	C100F	0.997
11:2159897:A:C	C96W	0.997
11:2159898:C:G	C96S	0.997
11:2159899:A:T	C96S	0.997
11:2159901:C:A	C95F	0.997
11:2159901:C:T	C95Y	0.997
11:2159902:A:G	C95R	0.997
11:2159860:A:G	C109R	0.996
11:2159898:C:A	C96F	0.996
11:2159899:A:G	C96R	0.995
11:2159913:A:T	I91N	0.995
11:2159863:A:G	Y108H	0.994
11:2159913:A:C	I91S	0.993
11:2159863:A:C	Y108D	0.992

dbSNP variants (sampled 300 via entrez): RS1000421369 (11:2162668 C>G), RS1000860662 (11:2162456 C>T), RS1001287209 (11:2163181 G>C), RS1002709574 (11:2159417 C>A,G,T), RS1003572987 (11:2161495 C>G,T), RS1003625587 (11:2162147 C>T), RS1005029940 (11:2161033 T>C), RS1006077352 (11:2160172 T>C), RS1006248935 (11:2162141 G>A,C), RS1006632102 (11:2163072 G>A), RS1007946619 (11:2159662 C>A,T), RS1009600432 (11:2162327 A>G), RS1009959779 (11:2162190 C>G,T), RS1010541017 (11:2160735 G>A,T), RS1011086548 (11:2159497 G>C)

Disease associations

OMIM: gene MIM:176730 | disease phenotypes: MIM:613370, MIM:125852, MIM:616214, MIM:618858, MIM:606176, MIM:222100, MIM:605407, MIM:617892, MIM:125853

GenCC curated gene-disease

Disease	Classification	Inheritance
diabetes mellitus, permanent neonatal 4	Strong	Autosomal dominant
transient neonatal diabetes mellitus	Strong	Autosomal dominant
permanent neonatal diabetes mellitus	Strong	Autosomal dominant
type 1 diabetes mellitus 2	Strong	Autosomal dominant
maturity-onset diabetes of the young type 10	Strong	Autosomal dominant
hyperproinsulinemia	Strong	Autosomal dominant
maturity-onset diabetes of the young	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
monogenic diabetes	Definitive	AR
monogenic diabetes	Definitive	AD

Mondo (14): maturity-onset diabetes of the young type 10 (MONDO:0013240), type 1 diabetes mellitus 2 (MONDO:0007454), hyperproinsulinemia (MONDO:0014535), diabetes mellitus, permanent neonatal 4 (MONDO:0030089), neonatal diabetes mellitus (MONDO:0016391), permanent neonatal diabetes mellitus (MONDO:0100164), type 1 diabetes mellitus (MONDO:0005147), monogenic diabetes (MONDO:0015967), TH-deficient dopa-responsive dystonia (MONDO:0011551), diabetes mellitus (MONDO:0005015), amyotrophic lateral sclerosis, susceptibility to, 24 (MONDO:0054750), type 2 diabetes mellitus (MONDO:0005148), transient neonatal diabetes mellitus (MONDO:0020525), maturity-onset diabetes of the young (MONDO:0018911)

Orphanet (6): MODY (Orphanet:552), Neonatal diabetes mellitus (Orphanet:224), Isolated permanent neonatal diabetes mellitus (Orphanet:99885), Rare genetic diabetes mellitus (Orphanet:183625), Autosomal recessive dopa-responsive dystonia (Orphanet:101150), NON RARE IN EUROPE: Diabetes mellitus type 1 (Orphanet:243377)

HPO phenotypes

65 total (30 of 65 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000077	Abnormality of the kidney
HP:0000107	Renal cyst
HP:0000112	Nephropathy
HP:0000119	Abnormality of the genitourinary system
HP:0000124	Renal tubular dysfunction
HP:0000365	Hearing impairment
HP:0000488	Retinopathy
HP:0000819	Diabetes mellitus
HP:0000825	Hyperinsulinemic hypoglycemia
HP:0000831	Insulin-resistant diabetes mellitus
HP:0000842	Hyperinsulinemia
HP:0000857	Neonatal insulin-dependent diabetes mellitus
HP:0000956	Acanthosis nigricans
HP:0001249	Intellectual disability
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001259	Coma
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001488	Bilateral ptosis
HP:0001508	Failure to thrive
HP:0001511	Intrauterine growth retardation
HP:0001513	Obesity
HP:0001518	Small for gestational age
HP:0001520	Large for gestational age
HP:0001627	Abnormal heart morphology
HP:0001738	Exocrine pancreatic insufficiency
HP:0001824	Weight loss

GWAS associations

34 associations (top):

Study	Trait	p-value
GCST000038_11	Type 1 diabetes	2.000000e-07
GCST000054_1	Type 1 diabetes	4.000000e-09
GCST000392_32	Type 1 diabetes	4.000000e-48
GCST000488_11	Prostate cancer	3.000000e-33
GCST001191_21	Type 1 diabetes	5.000000e-196
GCST001370_17	Prostate cancer (SNP x SNP interaction)	4.000000e-06
GCST001370_18	Prostate cancer (SNP x SNP interaction)	4.000000e-06
GCST001370_43	Prostate cancer (SNP x SNP interaction)	3.000000e-06
GCST001370_45	Prostate cancer (SNP x SNP interaction)	4.000000e-06
GCST002112_1	Celiac disease	7.000000e-06
GCST003097_23	Pediatric autoimmune diseases	8.000000e-11
GCST005146_23	Birth weight	7.000000e-10
GCST005536_25	Type 1 diabetes	6.000000e-10
GCST005536_49	Type 1 diabetes	1.000000e-100
GCST006196_1	Type 1 diabetes in high risk HLA genotype individuals (time to event)	3.000000e-07
GCST006197_5	Type 1 diabetes autoantibodies in high risk HLA genotype individuals (time to event)	1.000000e-07
GCST006197_8	Type 1 diabetes autoantibodies in high risk HLA genotype individuals (time to event)	6.000000e-06
GCST007246_2	Latent autoimmune diabetes vs. type 2 diabetes	1.000000e-18
GCST007847_40	Type 2 diabetes	3.000000e-13
GCST008114_9	Type 2 diabetes	2.000000e-07
GCST008377_1	Type 1 diabetes	1.000000e-06
GCST008464_3	Type 2 diabetes	2.000000e-08
GCST009379_367	Type 2 diabetes	2.000000e-06
GCST009379_368	Type 2 diabetes	2.000000e-08
GCST009379_369	Type 2 diabetes	4.000000e-08
GCST009379_370	Type 2 diabetes	1.000000e-06
GCST009379_371	Type 2 diabetes	4.000000e-26
GCST009916_5	Type 1 diabetes	1.000000e-13
GCST010118_120	Type 2 diabetes	1.000000e-16
GCST010681_2	Type 1 diabetes	1.000000e-160

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004344	birth weight
EFO:0000409	disease free survival
EFO:0000482	event free survival time
EFO:0004866	autoantibody measurement
EFO:0009706	latent autoimmune diabetes in adults

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D003920	Diabetes Mellitus	C18.452.394.750; C19.246
D003922	Diabetes Mellitus, Type 1	C18.452.394.750.124; C19.246.267; C20.111.327
D003924	Diabetes Mellitus, Type 2	C18.452.394.750.149; C19.246.300
C565100	Diabetes Mellitus, Insulin-Dependent, 2 (supp.)
C563425	Diabetes Mellitus, Permanent Neonatal (supp.)
C562776	Hyperproinsulinemia (supp.)
C562772	Mason-Type Diabetes (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5881 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

281 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Glucose	decreases oxidation, decreases uptake, affects cotreatment, decreases expression, affects response to substance (+18 more)	51
Rosiglitazone	affects cotreatment, increases expression, decreases reaction, increases secretion, increases reaction (+6 more)	24
Dexamethasone	increases response to substance, decreases reaction, increases expression, decreases expression, increases phosphorylation (+9 more)	23
1-Methyl-3-isobutylxanthine	increases expression, increases secretion, decreases expression, decreases secretion, affects reaction (+8 more)	20
sodium arsenite	decreases phosphorylation, affects reaction, increases secretion, increases uptake, decreases activity (+9 more)	11
Troglitazone	increases uptake, increases reaction, decreases expression, increases response to substance, affects cotreatment (+2 more)	9
Metformin	decreases uptake, increases activity, increases expression, increases reaction, decreases expression (+9 more)	9
bisphenol A	increases secretion, decreases expression, affects reaction, increases uptake, affects expression (+6 more)	8
Resveratrol	decreases reaction, increases reaction, increases secretion, decreases response to substance, increases expression (+2 more)	8
Deoxyglucose	increases uptake, increases reaction, affects reaction, decreases reaction	8
Wortmannin	affects localization, decreases reaction, decreases expression, decreases response to substance, increases expression (+2 more)	6
Blood Glucose	decreases reaction, increases reaction, increases secretion, affects abundance, decreases activity (+1 more)	5
Diethylhexyl Phthalate	affects cotreatment, decreases expression, decreases reaction, affects reaction, increases secretion (+3 more)	5
Indomethacin	increases expression, decreases secretion, affects expression, decreases reaction, affects cotreatment (+2 more)	5
Nitric Oxide	decreases reaction, affects cotreatment, decreases chemical synthesis, affects reaction, increases secretion (+5 more)	5
Quercetin	decreases reaction, increases phosphorylation, increases response to substance, affects phosphorylation, affects reaction (+3 more)	5
Terbutaline	decreases reaction, increases expression	5
Octreotide	decreases expression, decreases secretion, affects secretion, decreases reaction, increases expression	5
Palmitic Acid	affects reaction, affects phosphorylation, decreases expression, decreases reaction, increases uptake (+5 more)	5
tributyltin	decreases reaction, increases reaction, increases secretion, affects cotreatment, increases expression (+1 more)	4
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	affects cotreatment, decreases reaction, increases phosphorylation, decreases response to substance, increases expression	4
2-chloro-5-nitrobenzanilide	increases secretion, increases reaction, decreases expression, affects cotreatment, decreases reaction (+1 more)	4
Olanzapine	increases expression, increases secretion	4
Pioglitazone	increases reaction, affects expression, affects cotreatment, decreases reaction, increases secretion (+4 more)	4
Orlistat	decreases reaction, increases expression, increases reaction, affects expression, affects cotreatment (+1 more)	4
Bezafibrate	decreases reaction, affects expression, decreases expression, increases activity, increases expression (+4 more)	4
Epinephrine	decreases expression, decreases reaction, affects cotreatment, increases phosphorylation, decreases secretion	4
Hydrocortisone	affects reaction, increases expression, decreases reaction, affects cotreatment, decreases expression (+1 more)	4
bisphenol F	decreases expression, affects cotreatment, affects expression, increases expression, increases secretion	3
Fulvestrant	increases reaction, increases secretion, affects reaction, affects cotreatment, increases methylation (+2 more)	3

ChEMBL screening assays

8 unique, capped per target: 7 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1931012	Binding	Binding affinity to human insulin monomer by fluorescence intensity assay	Synthesis and in vitro evaluation of fluorinated styryl benzazoles as amyloid-probes. — Bioorg Med Chem
CHEMBL4187589	ADMET	Effect on DTT-induced insulin (unknown origin) denaturation and aggregation at 10 uM pre-incubated for 5 mins before DTT addition	Synthesis and biological evaluation of anti-cancer agents that selectively inhibit Her2 over-expressed breast cancer cell growth via down-regulation of Her2 protein. — Bioorg Med Chem Lett

Cellosaurus cell lines

39 cell lines: 32 cancer cell line, 3 spontaneously immortalized cell line, 2 transformed cell line, 1 induced pluripotent stem cell, 1 telomerase immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1G39	AtT-20ins4b/1	Cancer cell line	Sex unspecified
CVCL_1G40	AtT-20ins	Cancer cell line	Sex unspecified
CVCL_2G77	INS-1 834/40	Cancer cell line	Male
CVCL_2G78	INS-1 833/15	Cancer cell line	Male
CVCL_2G79	INS-1 833/117	Cancer cell line	Male
CVCL_6566	CGT-6	Cancer cell line	Sex unspecified
CVCL_7226	INS-1 832/13	Cancer cell line	Male
CVCL_A6AC	Tet-293/Ins6	Transformed cell line	Female
CVCL_A9YK	MNDINSi001-A	Induced pluripotent stem cell	Female
CVCL_B6ER	YOCK-13	Telomerase immortalized cell line	Sex unspecified

Clinical trials (associated diseases)

317 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02624817	PHASE4	COMPLETED	Long-Term Sulfonylurea Response in KCNJ11 Neonatal Diabetes
NCT02624830	PHASE4	UNKNOWN	Long-Term Sulfonylurea Response in ABCC8 Neonatal Diabetes (SuResponsSUR)
NCT00145353	PHASE4	UNKNOWN	Insulin NovoRapid Versus Actrapid in Treatment of Type 1 Diabetic Patients During Daily Adjustment of Insulin Dose
NCT00145379	PHASE4	COMPLETED	The Effect of Metformin in Overweight Patients With Dysregulated Type 1 Diabetes Mellitus
NCT00206401	PHASE4	COMPLETED	Lantus in the Treatment of Type 1 Diabetes Children
NCT00276393	PHASE4	COMPLETED	Treatment Trial Evaluating Long Acting Insulin in Type 1 Diabetes
NCT00291772	PHASE4	COMPLETED	Continuous Subcutaneous Infusion of Pramlintide and Insulin
NCT00315952	PHASE4	COMPLETED	Study to Estimate the Effects of Inhaled Versus Intravenous (IV) Infusion of Human Insulin in Subjects With Type 1 Diabetes
NCT00340613	PHASE4	COMPLETED	Lunch Time Insulin Injection by School Nurse for Poorly Controlled Diabetes
NCT00346996	PHASE4	COMPLETED	Insulin Analogues and Severe Hypoglycaemia
NCT00360984	PHASE4	COMPLETED	Prevention of Severe Hypoglycemia in Type 1 Diabetes
NCT00372086	PHASE4	COMPLETED	Rosiglitazone and Insulin in T1DM Adolescents
NCT00442767	PHASE4	COMPLETED	Post-meal Insulin Dosing With Adjuvant Pre-meal Pramlintide in Children With Type 1 Diabetes Mellitus
NCT00453934	PHASE4	TERMINATED	Patient Preference of h-Patch vs. Pen or Needle/Syringe as Insulin Administration Device
NCT00461331	PHASE4	COMPLETED	Comparison of Insulins Aspart and Lispro in Insulin Pumps
NCT00472875	PHASE4	UNKNOWN	Do Sulphonylureas Preserve Cortical Function During Hypoglycaemia?
NCT00497536	PHASE4	COMPLETED	Pharmacokinetics of IAsp Following CSII in Patients With T1DM
NCT00502138	PHASE4	COMPLETED	A Pilot Study of Continuous Subcutaneous Pramlintide Infusion Therapy in Patients With Type 1 Diabetes
NCT00505882	PHASE4	WITHDRAWN	Efficacy of Pramlintide on Prevention of Weight Gain Early Onset of Type 1 Diabetes
NCT00530023	PHASE4	COMPLETED	Feasibility Study for Training Pump Naïve Subjects To Use The Paradigm® System And Evaluate Effectiveness
NCT00542399	PHASE4	COMPLETED	Comparing the Metabolic Control of Once to Twice-daily Insulin Detemir Injections
NCT00564395	PHASE4	COMPLETED	Detemir: Role in Type 1 Diabetes
NCT00814476	PHASE4	COMPLETED	The Effects of Regular Home Use Vs Diabetic Team- Supported Use of the Medtronic CareLink Therapy Management System.
NCT00898534	PHASE4	COMPLETED	Effect of Immediate Hemoglobin A1c on Glycemic Control in Children With Type I Diabetes Mellitus
NCT00913497	PHASE4	COMPLETED	The Effect of Insulin Glulisine Compared With Insulin Aspart on Breakfast Post Prandial Glucose Levels in Prepubertal Children
NCT00978796	PHASE4	COMPLETED	Assessing Glucose Effects of Sitagliptin (Januvia) in Adult Patients With Type 1 Diabetes
NCT01019486	PHASE4	COMPLETED	Regadenoson Blood Flow in Type 1 Diabetes (RABIT1D)
NCT01235819	PHASE4	COMPLETED	Comparison Between GLP 1 Analogues and DPP 4 Inhibitors in Type 1 Diabetes Mellitus
NCT01269034	PHASE4	COMPLETED	New Onset Type 1 Diabetes: Role of Exenatide
NCT01269047	PHASE4	COMPLETED	Use of Exenatide and Pramlintide to Decrease Post-prandial Hyperglycemia
NCT01280682	PHASE4	COMPLETED	Immune Intervention With Rituximab to Preserve Beta Cell Function in Early Onset Type 1 Diabetes
NCT01331343	PHASE4	COMPLETED	Effectiveness Study of the Guardian RT in Type 1 Diabetics
NCT01351857	PHASE4	COMPLETED	Diabetes Care Management Compared to Standard Diabetes Care in Adolescents and Young Adults With Type 1 Diabetes
NCT01390480	PHASE4	COMPLETED	Effects of Vitamin D Supplementation in Subjects With New Onset of Type 1 Diabetes
NCT01400659	PHASE4	COMPLETED	Pizza-Salami Study in Children and Adolescents With Type 1 Diabetes
NCT01454700	PHASE4	COMPLETED	Effect of CSII and CGM on Progression of Late Diabetic Complications
NCT01488136	PHASE4	COMPLETED	Use of Diazoxide in Acute Hypoglycaemia
NCT01497912	PHASE4	COMPLETED	Treatment Effects of Atorvastatin on Hemostasis and Skin Microcirculation in Patients With Type 1 Diabetes
NCT01526733	PHASE4	COMPLETED	Randomized, Double Blind, 2 Way Crossover Study of CSII With, Versus Without, Pretreatment With Human Hyaluronidase
NCT01668485	PHASE4	COMPLETED	Mechanisms of Glucose Counterregulation in Pancreatic Islet Transplantation