Genomes and Genes
Gene Symbol: Ins2
Description: insulin 2
Alias: CP-II, insulin-2, C-peptide
- Lomedico P, Rosenthal N, Efstratidadis A, Gilbert W, Kolodner R, Tizard R. The structure and evolution of the two nonallelic rat preproinsulin genes. Cell. 1979;18:545-58 pubmed..Calculations based on the divergence of the two preproinsulin nucleotide and amino acid sequences indicate that these genes are the products of a recent duplication. Thus one of the genes gained or lost an intron since that time. ..
- Ward W, LaCava E, Paquette T, Beard J, Wallum B, Porte D. Disproportionate elevation of immunoreactive proinsulin in type 2 (non-insulin-dependent) diabetes mellitus and in experimental insulin resistance. Diabetologia. 1987;30:698-702 pubmed..abstract truncated at 250 words) ..
- Crabtree J, Scacheri P, Ward J, McNally S, Swain G, Montagna C, et al. Of mice and MEN1: Insulinomas in a conditional mouse knockout. Mol Cell Biol. 2003;23:6075-85 pubmed..Comparative genomic hybridization of beta cell tumor DNA from these mice reveals duplication of chromosome 11, potentially revealing regions of interest with respect to tumorigenesis. ..
- Oyadomari S, Koizumi A, Takeda K, Gotoh T, Akira S, Araki E, et al. Targeted disruption of the Chop gene delays endoplasmic reticulum stress-mediated diabetes. J Clin Invest. 2002;109:525-32 pubmed..The Akita mouse, which carries a conformation-altering missense mutation (Cys96Tyr) in Insulin 2, likewise exhibits hyperglycemia and a reduced beta cell mass...
- Kitamura T, Nakae J, Kitamura Y, Kido Y, Biggs W, Wright C, et al. The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth. J Clin Invest. 2002;110:1839-47 pubmed..We propose that insulin/IGFs regulate beta cell proliferation by relieving Foxo1 inhibition of Pdx1 expression in a subset of cells embedded within pancreatic ducts. ..
- Graciano M, Santos L, Curi R, Carpinelli A. NAD(P)H oxidase participates in the palmitate-induced superoxide production and insulin secretion by rat pancreatic islets. J Cell Physiol. 2011;226:1110-7 pubmed publisher..In conclusion, NAD(P)H oxidase is an important source of superoxide in pancreatic islets and the activity of NAD(P)H oxidase is involved in the control of insulin secretion by palmitate. ..
- Amyot J, Benterki I, Fontes G, Hagman D, Ferdaoussi M, Teodoro T, et al. Binding of activating transcription factor 6 to the A5/Core of the rat insulin II gene promoter does not mediate its transcriptional repression. J Mol Endocrinol. 2011;47:273-83 pubmed publisher..Therefore, although ATF6 binds directly to the A5/Core of the rat insulin II gene promoter, this direct binding does not appear to contribute to its repressive activity. ..
- Navaneethan S, Beddhu S. Associations of serum uric acid with cardiovascular events and mortality in moderate chronic kidney disease. Nephrol Dial Transplant. 2009;24:1260-6 pubmed publisher..The presence of CKD attenuates the associations of uric acid with mortality. Interventional studies are warranted to establish the biological role of hyperuricaemia in mortality in non-CKD and CKD populations. ..
- Giddings S, Carnaghi L. Rat insulin II gene expression by extraplacental membranes. A non-pancreatic source for fetal insulin. J Biol Chem. 1989;264:9462-9 pubmed..These studies indicate that yolk sac is a source for insulin during fetal development and that the mechanisms regulating insulin gene expression in this tissue differ from those in pancreatic beta cells. ..
- Kohn A, Takeuchi F, Roth R. Akt, a pleckstrin homology domain containing kinase, is activated primarily by phosphorylation. J Biol Chem. 1996;271:21920-6 pubmed..Phosphorylation of this fusion protein still critically contributes toward its increased activity. The sum of these results indicates that the primary mechanism of Akt activation is via protein phosphorylation. ..
- Chan S, Noyes B, Agarwal K, Steiner D. Construction and selection of recombinant plasmids containing full-length complementary DNAs corresponding to rat insulins I and II. Proc Natl Acad Sci U S A. 1979;76:5036-40 pubmed..Comparison of the amino acid sequence of the prepeptides of rat preproinsulin I and II shows that three conservative amino acid substitutions have occurred in this region of the molecule. ..
- Denko C, Boja B, Moskowitz R. Growth promoting peptides in osteoarthritis: insulin, insulin-like growth factor-1, growth hormone. J Rheumatol. 1990;17:1217-21 pubmed..Our findings support a role for these peptides in the pathophysiology of OA. ..
- Brands M, Harrison D, Keen H, Gardner A, Shek E, Hall J. Insulin-induced hypertension in rats depends on an intact renin-angiotensin system. Hypertension. 1997;29:1014-9 pubmed..These results indicate that insulin-induced hypertension in rats depends on angiotensin II and suggest that a reduction in glomerular filtration rate contributes to the shift in pressure natriuresis. ..
- Youngren J. Regulation of insulin receptor function. Cell Mol Life Sci. 2007;64:873-91 pubmed..The impact of these processes on the conformational changes and phosphorylation events required for full signaling activity, as well as the role of these mechanisms in human disease, is reviewed in this article. ..
- Fang D, Guan H, Liu J, Wei G, Ke W, Yao B, et al. Early intensive insulin therapy attenuates the p38 pathway in the renal cortex and indices of nephropathy in diabetic rats. Endocr J. 2012;59:81-90 pubmed..However, late insulin therapy did not abrogate the increased renal cortical p38 MAPK pathway activation in diabetic rats and led to glomerular hypertrophy and extracellular matrix expansion. ..
- Park K, Li Q, Rask Madsen C, Mima A, Mizutani K, Winnay J, et al. Serine phosphorylation sites on IRS2 activated by angiotensin II and protein kinase C to induce selective insulin resistance in endothelial cells. Mol Cell Biol. 2013;33:3227-41 pubmed publisher..Thus, AngII or PKC? activation can phosphorylate Ser303 and Ser675 in IRS2 to inhibit insulin-induced p-Tyr911 and its anti-atherogenic actions (p-Akt/eNOS) in endothelial cells. ..
- Acevedo C, Márquez J, Rojas S, Bravo I. Insulin and nitric oxide stimulates glucose transport in human placenta. Life Sci. 2005;76:2643-53 pubmed..Taken together, these findings indicate that insulin and NO stimulate glucose uptake in human placenta and suggest that both potential regulators of glucose transport use different signaling pathways. ..
- Smith G, Ciszak E, Pangborn W. A novel complex of a phenolic derivative with insulin: structural features related to the T-->R transition. Protein Sci. 1996;5:1502-11 pubmed..A procedure is also described for an alternate method of interframe scaling and merging intensity data from an image plate detector. ..
- Freund G, Kulas D, Mooney R. Insulin and IGF-1 increase mitogenesis and glucose metabolism in the multiple myeloma cell line, RPMI 8226. J Immunol. 1993;151:1811-20 pubmed..Thus, functional insulin and IGF-1 receptors are present in myeloma cell lines. Through these receptors, insulin and IGF-1 regulate mitogenesis and glucose metabolism, and may be important in potentiating plasma cell malignancy. ..
- Reverchon M, Rame C, Cognie J, Briant E, Elis S, Guillaume D, et al. Resistin in dairy cows: plasma concentrations during early lactation, expression and potential role in adipose tissue. PLoS ONE. 2014;9:e93198 pubmed publisher..Resistin is expressed in bovine mature adipocytes and promotes lipid mobilization in adipose explants in vitro. ..
- James R, James A, Drewett R, Cheetham T. Milk intake and feeding behavior in the first week of life and its relationship to cord blood ghrelin, leptin, and insulin concentrations. Pediatr Res. 2007;62:695-9 pubmed..Total cord ghrelin and leptin are not directly related to milk intake or feed frequency in the first week of life. Circulating insulin concentrations may have a role in the initiation of feeding behavior. ..
- Guest P, Abdel Halim S, Gross D, Clark A, Poitout V, Amaria R, et al. Proinsulin processing in the diabetic Goto-Kakizaki rat. J Endocrinol. 2002;175:637-47 pubmed..Thus, the marked changes in islet morphology and PC2 expression did not impact the rate or extent of proinsulin processing either in vitro or in vivo in this experimental model. ..
- Dayyani F, Zurita A, Nogueras Gonzalez G, Slack R, Millikan R, Araujo J, et al. The combination of serum insulin, osteopontin, and hepatocyte growth factor predicts time to castration-resistant progression in androgen dependent metastatic prostate cancer- an exploratory study. BMC Cancer. 2016;16:721 pubmed publisher..001). Pretreatment serum insulin, HGF, OPN, and C-peptide levels can predict PFS in men with mADPC treated with ADT. Risk groups based on these factors are superior predictors of PFS than each marker alone. ..
- Kittl M, Beyreis M, Tumurkhuu M, Furst J, Helm K, Pitschmann A, et al. Quercetin Stimulates Insulin Secretion and Reduces the Viability of Rat INS-1 Beta-Cells. Cell Physiol Biochem. 2016;39:278-93 pubmed publisher..Long term application of quercetin inhibits cell proliferation and induces apoptosis, most likely by inhibition of PI3K/Akt signaling. ..
- De Felice F, Vieira M, Bomfim T, Decker H, Velasco P, Lambert M, et al. Protection of synapses against Alzheimer's-linked toxins: insulin signaling prevents the pathogenic binding of Abeta oligomers. Proc Natl Acad Sci U S A. 2009;106:1971-6 pubmed publisher..The finding that synapse vulnerability to ADDLs can be mitigated by insulin suggests that bolstering brain insulin signaling, which can decline with aging and diabetes, could have significant potential to slow or deter AD pathogenesis. ..
- Yilmaz O, Kucuk M, Ilgin A, Dagdelen M. Assessment of insulin sensitivity/resistance and their relations with leptin concentrations and anthropometric measures in a pregnant population with and without gestational diabetes mellitus. J Diabetes Complications. 2010;24:109-14 pubmed publisher..We suggest that by simply evaluating SFT, we may hold a view about BFP and leptin concentrations and insulin sensitivity in pregnant women. ..
- Krieger Brauer H, Medda P, Kather H. Insulin-induced activation of NADPH-dependent H2O2 generation in human adipocyte plasma membranes is mediated by Galphai2. J Biol Chem. 1997;272:10135-43 pubmed..Thus, NADPH oxidase is the first example of an effector system that is coupled to the insulin receptor via a heterotrimeric G protein. ..
- Nair K, Ford G, Halliday D. Effect of intravenous insulin treatment on in vivo whole body leucine kinetics and oxygen consumption in insulin-deprived type I diabetic patients. Metabolism. 1987;36:491-5 pubmed
- Hunter S, Garvey W. Insulin action and insulin resistance: diseases involving defects in insulin receptors, signal transduction, and the glucose transport effector system. Am J Med. 1998;105:331-45 pubmed
- Støy J, Edghill E, Flanagan S, Ye H, Paz V, Pluzhnikov A, et al. Insulin gene mutations as a cause of permanent neonatal diabetes. Proc Natl Acad Sci U S A. 2007;104:15040-4 pubmed..has been described in both the Akita and Munich mouse models that have dominant-acting missense mutations in the Ins2 gene, leading to loss of beta cell function and mass...
- Tsuji Y, Kaburagi Y, Terauchi Y, Satoh S, Kubota N, Tamemoto H, et al. Subcellular localization of insulin receptor substrate family proteins associated with phosphatidylinositol 3-kinase activity and alterations in lipolysis in primary mouse adipocytes from IRS-1 null mice. Diabetes. 2001;50:1455-63 pubmed
- Skyler J, Hollander P, Jovanovic L, Klioze S, Krasner A, Riese R, et al. Safety and efficacy of inhaled human insulin (Exubera) during discontinuation and readministration of therapy in adults with type 1 diabetes: A 3-year randomized controlled trial. Diabetes Res Clin Pract. 2008;82:238-46 pubmed publisher..EXU readministration is not associated with an augmented IAb response. ..
- Sun J, Jin T. Both Wnt and mTOR signaling pathways are involved in insulin-stimulated proto-oncogene expression in intestinal cells. Cell Signal. 2008;20:219-29 pubmed..Our observations support the existence of crosstalk between insulin and Wnt signaling pathways, and suggest that the crosstalk involves a PKB-independent mechanism. ..
- Soos M, Field C, Siddle K. Purified hybrid insulin/insulin-like growth factor-I receptors bind insulin-like growth factor-I, but not insulin, with high affinity. Biochem J. 1993;290 ( Pt 2):419-26 pubmed
- Steiner D, Clark J, Nolan C, Rubenstein A, Margoliash E, Aten B, et al. Proinsulin and the biosynthesis of insulin. Recent Prog Horm Res. 1969;25:207-82 pubmed
- Doronzo G, Russo I, Mattiello L, Anfossi G, Bosia A, Trovati M. Insulin activates vascular endothelial growth factor in vascular smooth muscle cells: influence of nitric oxide and of insulin resistance. Eur J Clin Invest. 2004;34:664-73 pubmed..The insulin action on both nitric oxide and VEGF is impaired in VSMCs from Zucker fa/fa rats, an animal model of metabolic and vascular insulin-resistance. ..
- Malide D, Seidah N, Chretien M, Bendayan M. Electron microscopic immunocytochemical evidence for the involvement of the convertases PC1 and PC2 in the processing of proinsulin in pancreatic beta-cells. J Histochem Cytochem. 1995;43:11-9 pubmed..Co-expression of PC1 and PC2 with proinsulin in islet beta-cells indicates that these proteases are actively involved, probably in a sequential manner, in the conversion of proinsulin into insulin. ..
- Le Stunff C, Fallin D, Schork N, Bougneres P. The insulin gene VNTR is associated with fasting insulin levels and development of juvenile obesity. Nat Genet. 2000;26:444-6 pubmed..Young obese patients homozygous for class I VNTR alleles secrete more insulin than those with other genotypes. ..
- Bachar Wikstrom E, Wikstrom J, Ariav Y, Tirosh B, Kaiser N, Cerasi E, et al. Stimulation of autophagy improves endoplasmic reticulum stress-induced diabetes. Diabetes. 2013;62:1227-37 pubmed publisher..The beneficial effects of rapamycin in this context strictly depend on autophagy; therefore, stimulating autophagy may become a therapeutic approach for diabetes. ..
- Allister E, Pal S, Thomson A, Helmerhorst E, Mamo J. Insulin decreases the secretion of apoB-100 from hepatic HepG2 cells but does not decrease the secretion of apoB-48 from intestinal CaCo-2 cells. J Biomed Sci. 2004;11:789-98 pubmed..Therefore, insulin acutely decreases the secretion of apoB-100 in hepatic HepG2 cells, but does not acutely modulate the production or secretion of apoB-48 from CaCo-2 intestinal cells. ..
- Chu K, Tsai M. Neuronatin, a downstream target of BETA2/NeuroD1 in the pancreas, is involved in glucose-mediated insulin secretion. Diabetes. 2005;54:1064-73 pubmed..These results suggest for the first time an important role for NNAT in insulin secretion and for proper beta-cell function. ..
- Pierre E, Barrow R, Hawkins H, Nguyen T, Sakurai Y, Desai M, et al. Effects of insulin on wound healing. J Trauma. 1998;44:342-5 pubmed..Collagen type IV staining also increased after insulin therapy compared with placebo. Data indicate that high doses of insulin and glucose can be safely administered to massively burned patients to improve wound matrix formation. ..
- Arias A, Vélez Granell C, Mayer G, Bendayan M. Colocalization of chaperone Cpn60, proinsulin and convertase PC1 within immature secretory granules of insulin-secreting cells suggests a role for Cpn60 in insulin processing. J Cell Sci. 2000;113 ( Pt 11):2075-83 pubmed
- Hompesch M, Kollmeier A, Rave K, Heinemann L, Mitnick M, Davies S, et al. Glycemic exposure is affected favorably by inhaled human insulin (Exubera) as compared with subcutaneous insulin glargine (Lantus) in patients with type 2 diabetes. Diabetes Technol Ther. 2009;11:307-13 pubmed..4 for GLA. Prandial insulin therapy with EXU, using a higher daily insulin dose, reduces total daily glucose exposure--in particular postmeal glycemia--more effectively than a basal insulin analog. ..
- Lind J, Lindahl E, Perálvarez Marín A, Holmlund A, Jornvall H, Mäler L. Structural features of proinsulin C-peptide oligomeric and amyloid states. FEBS J. 2010;277:3759-68 pubmed publisher..This leads to the conclusion that the oligomerization of C-peptide may be relevant also at low concentrations. ..
- Bork Jensen J, Scheele C, Christophersen D, Nilsson E, Friedrichsen M, Fernandez Twinn D, et al. Glucose tolerance is associated with differential expression of microRNAs in skeletal muscle: results from studies of twins with and without type 2 diabetes. Diabetologia. 2015;58:363-73 pubmed publisher..The paradoxical findings in twins with overt diabetes and twins at increased risk of the disease underscore the complexity of the regulation of muscle insulin signalling in glucose homeostasis. ..
- Grunblatt E, Salkovic Petrisic M, Osmanovic J, Riederer P, Hoyer S. Brain insulin system dysfunction in streptozotocin intracerebroventricularly treated rats generates hyperphosphorylated tau protein. J Neurochem. 2007;101:757-70 pubmed..Brain insulin system dysfunction is discussed as possible pathological core in the generation of hyperphosphorylated tau protein as a morphological marker of sporadic Alzheimer's disease. ..
- Soares M, Schon E, Henderson A, Karathanasis S, Cate R, Zeitlin S, et al. RNA-mediated gene duplication: the rat preproinsulin I gene is a functional retroposon. Mol Cell Biol. 1985;5:2090-103 pubmed
- Romacho T, Azcutia V, Vázquez Bella M, Matesanz N, Cercas E, Nevado J, et al. Extracellular PBEF/NAMPT/visfatin activates pro-inflammatory signalling in human vascular smooth muscle cells through nicotinamide phosphoribosyltransferase activity. Diabetologia. 2009;52:2455-2463 pubmed publisher..Through its intrinsic NAMPT activity, ePBEF/NAMPT/visfatin appears to be a direct contributor to vascular inflammation, a key feature of atherothrombotic diseases linked to metabolic disorders. ..
- Kolb A, Rieder S, Born D, Giese N, Giese T, Rudofsky G, et al. Glucagon/insulin ratio as a potential biomarker for pancreatic cancer in patients with new-onset diabetes mellitus. Cancer Biol Ther. 2009;8:1527-33 pubmed..Therefore, this analysis might help to identify PDAC in patients with new-onset DM in the age group at risk. Larger clinical trials have to confirm these findings. ..
- Kitamura T, Kimura K, Jung B, Makondo K, Sakane N, Yoshida T, et al. Proinsulin C-peptide activates cAMP response element-binding proteins through the p38 mitogen-activated protein kinase pathway in mouse lung capillary endothelial cells. Biochem J. 2002;366:737-44 pubmed..These results indicate that C-peptide activates p38MAPK followed by MAPKAP-K2 to enhance DNA-CREB/ATF1 interactions. ..
- Font de Mora J, Esteban L, Burks D, Nunez A, Garces C, Garcia Barrado M, et al. Ras-GRF1 signaling is required for normal beta-cell development and glucose homeostasis. EMBO J. 2003;22:3039-49 pubmed..Thus, our observations demonstrate a novel and specific role for Ras-GRF1 pathways in the development and maintenance of normal beta-cell number and function. ..
- Toriumi C, Imai K. Determination of insulin in a single islet of Langerhans by high-performance liquid chromatography with fluorescence detection. Anal Chem. 2002;74:2321-7 pubmed..The method was applicable to the determination of rodent insulin in a single islet of Langerhans, and the results indicated its feasibility for the investigation of the pathophysiological roles of the isomers in diabetes in the rodent. ..
- Nault L, Vendrely C, Brechet Y, Bruckert F, Weidenhaupt M. Peptides that form ?-sheets on hydrophobic surfaces accelerate surface-induced insulin amyloidal aggregation. FEBS Lett. 2013;587:1281-6 pubmed publisher..Conversely, a peptide known to form ?-helices on hydrophobic surfaces delays insulin aggregation. ..
- Montessuit C, Papageorgiou I, Lerch R. Nuclear receptor agonists improve insulin responsiveness in cultured cardiomyocytes through enhanced signaling and preserved cytoskeletal architecture. Endocrinology. 2008;149:1064-74 pubmed..Thus, the stimulation of glucose uptake in response to insulin or metabolic stress is dependent in cardiomyocytes on the presence of intact microtubules. ..
- Varadi A, Tsuboi T, Rutter G. Myosin Va transports dense core secretory vesicles in pancreatic MIN6 beta-cells. Mol Biol Cell. 2005;16:2670-80 pubmed..We conclude that MyoVa-driven movements of vesicles along the cortical actin network are essential for the terminal stages of regulated exocytosis in beta-cells. ..