Ins2

Summary

Gene Symbol: Ins2
Description: insulin II
Alias: AA986540, Ins-2, InsII, Mody, Mody4, insulin-2, proinsulin
Species: mouse
Products:     Ins2

Top Publications

  1. Kakoki M, Sullivan K, Backus C, Hayes J, Oh S, Hua K, et al. Lack of both bradykinin B1 and B2 receptors enhances nephropathy, neuropathy, and bone mineral loss in Akita diabetic mice. Proc Natl Acad Sci U S A. 2010;107:10190-5 pubmed publisher
    ..nephropathy, neuropathy, and osteopathy in male mice heterozygous for the Akita diabetogenic mutation in the insulin 2 gene (Ins2)...
  2. Lynn F, Skewes Cox P, Kosaka Y, McManus M, Harfe B, German M. MicroRNA expression is required for pancreatic islet cell genesis in the mouse. Diabetes. 2007;56:2938-45 pubmed
    ..The expression of a unique profile of miRNAs is required during pancreas development and is necessary for beta-cell formation. ..
  3. Furuyama K, Kawaguchi Y, Akiyama H, Horiguchi M, Kodama S, Kuhara T, et al. Continuous cell supply from a Sox9-expressing progenitor zone in adult liver, exocrine pancreas and intestine. Nat Genet. 2011;43:34-41 pubmed publisher
    ..These results suggest interdependence between the structure and homeostasis of endodermal organs, with Sox9 expression being linked to progenitor status. ..
  4. Yamaguchi S, Ishihara H, Yamada T, Tamura A, Usui M, Tominaga R, et al. ATF4-mediated induction of 4E-BP1 contributes to pancreatic beta cell survival under endoplasmic reticulum stress. Cell Metab. 2008;7:269-76 pubmed publisher
    ..Thus, 4E-BP1 induction contributes to the maintenance of beta cell homeostasis during ER stress and is a potential therapeutic target for diabetes. ..
  5. Gao N, LeLay J, Vatamaniuk M, Rieck S, Friedman J, Kaestner K. Dynamic regulation of Pdx1 enhancers by Foxa1 and Foxa2 is essential for pancreas development. Genes Dev. 2008;22:3435-48 pubmed publisher
    ..Thus, the regulation of Pdx1 expression by Foxa1 and Foxa2 is a key early event controlling the expansion and differentiation of the pancreatic primordia. ..
  6. Meur G, Qian Q, Da Silva Xavier G, Pullen T, Tsuboi T, McKinnon C, et al. Nucleo-cytosolic shuttling of FoxO1 directly regulates mouse Ins2 but not Ins1 gene expression in pancreatic beta cells (MIN6). J Biol Chem. 2011;286:13647-56 pubmed publisher
    ..insulin-stimulated nuclear shuttling of FoxO1 in pancreatic ? cells and its consequences for preproinsulin (Ins1, Ins2) gene expression...
  7. van der Meulen T, Xie R, Kelly O, Vale W, Sander M, Huising M. Urocortin 3 marks mature human primary and embryonic stem cell-derived pancreatic alpha and beta cells. PLoS ONE. 2012;7:e52181 pubmed publisher
    ..Our study highlights important species differences in Ucn 3 expression, which have implications for its utility as a marker to identify mature beta cells in (re)programming strategies. ..
  8. Schaffer A, Freude K, Nelson S, Sander M. Nkx6 transcription factors and Ptf1a function as antagonistic lineage determinants in multipotent pancreatic progenitors. Dev Cell. 2010;18:1022-9 pubmed publisher
    ..Thus, cross-antagonism between Nkx6 and Ptf1a in multipotent progenitors governs the equilibrium between endocrine and acinar cell neogenesis required for normal pancreas development. ..
  9. Artner I, Blanchi B, Raum J, Guo M, Kaneko T, Cordes S, et al. MafB is required for islet beta cell maturation. Proc Natl Acad Sci U S A. 2007;104:3853-8 pubmed
    ..These results demonstrate that MafB plays a previously uncharacterized role by regulating transcription of key factors during development that are required for the production of mature alpha and beta cells. ..

More Information

Publications90

  1. Li S, Francisco A, Munroe R, Schimenti J, Long Q. SEL1L deficiency impairs growth and differentiation of pancreatic epithelial cells. BMC Dev Biol. 2010;10:19 pubmed publisher
    ..Together, these data suggest that Sel1l is essential for the growth and differentiation of endoderm-derived pancreatic epithelial cells during mouse embryonic development. ..
  2. Greiner T, Kesavan G, Ståhlberg A, Semb H. Rac1 regulates pancreatic islet morphogenesis. BMC Dev Biol. 2009;9:2 pubmed publisher
    ..Our results further emphasize Rac1 as a key regulator of cell migration and cell adhesion during tissue and organ morphogenesis. ..
  3. Johansson J, Voss U, Kesavan G, Kostetskii I, Wierup N, Radice G, et al. N-cadherin is dispensable for pancreas development but required for beta-cell granule turnover. Genesis. 2010;48:374-81 pubmed publisher
    ..The number of insulin secretory granules is significantly reduced in N-cadherin-deficient beta-cells, and as a consequence insulin secretion is decreased. ..
  4. Seymour P, Freude K, Tran M, Mayes E, Jensen J, Kist R, et al. SOX9 is required for maintenance of the pancreatic progenitor cell pool. Proc Natl Acad Sci U S A. 2007;104:1865-70 pubmed
    ..These findings will be of major significance for the development of in vitro protocols for cell replacement therapies. ..
  5. Brissova M, Shostak A, Shiota M, Wiebe P, Poffenberger G, Kantz J, et al. Pancreatic islet production of vascular endothelial growth factor--a is essential for islet vascularization, revascularization, and function. Diabetes. 2006;55:2974-85 pubmed
    ..Factors modulating VEGF-A expression may influence islet vascularity and, consequently, the amount of insulin delivered into the systemic circulation. ..
  6. Awad A, Kinsey G, Khutsishvili K, Gao T, Bolton W, Okusa M. Monocyte/macrophage chemokine receptor CCR2 mediates diabetic renal injury. Am J Physiol Renal Physiol. 2011;301:F1358-66 pubmed publisher
    ..We report that pharmacological blockade or genetic deficiency of CCR2 confers kidney protection in Ins2(Akita) and streptozotocin (STZ)-induced diabetic kidney disease...
  7. Kim S, Moley K. Paternal effect on embryo quality in diabetic mice is related to poor sperm quality and associated with decreased glucose transporter expression. Reproduction. 2008;136:313-22 pubmed publisher
    ..This is the first study to link a paternal metabolic abnormality to a sperm effect on cell division and subsequent embryonic development. ..
  8. Stiles B, Kuralwalla Martinez C, Guo W, Gregorian C, Wang Y, Tian J, et al. Selective deletion of Pten in pancreatic beta cells leads to increased islet mass and resistance to STZ-induced diabetes. Mol Cell Biol. 2006;26:2772-81 pubmed
    ..Our data demonstrate that PTEN loss in beta cells is not tumorigenic but beneficial. This suggests that modulating the PTEN-controlled signaling pathway is a potential approach for beta-cell protection and regeneration therapies. ..
  9. Nekrep N, Wang J, Miyatsuka T, German M. Signals from the neural crest regulate beta-cell mass in the pancreas. Development. 2008;135:2151-60 pubmed publisher
    ..2 form a non-cell-autonomous feedback loop that links the neural crest with the pancreatic epithelium, regulates the size of the beta-cell population, and thereby impacts insulin-secretory capacity and energy homeostasis. ..
  10. Diaferia G, Jimenez Caliani A, Ranjitkar P, Yang W, Hardiman G, Rhodes C, et al. ?1 integrin is a crucial regulator of pancreatic ?-cell expansion. Development. 2013;140:3360-72 pubmed publisher
    ..Collectively, our results demonstrate that ?1 integrin receptors function as crucial positive regulators of ?-cell expansion. ..
  11. Zhang W, Feng D, Li Y, Iida K, McGrath B, Cavener D. PERK EIF2AK3 control of pancreatic beta cell differentiation and proliferation is required for postnatal glucose homeostasis. Cell Metab. 2006;4:491-7 pubmed
    ..exhibit severe defects in fetal/neonatal beta cell proliferation and differentiation, resulting in low beta cell mass, defects in proinsulin trafficking, and abrogation of insulin secretion that culminate in permanent neonatal diabetes.
  12. Cras Méneur C, Li L, Kopan R, Permutt M. Presenilins, Notch dose control the fate of pancreatic endocrine progenitors during a narrow developmental window. Genes Dev. 2009;23:2088-101 pubmed publisher
  13. Jasinski J, Yu L, Nakayama M, Li M, Lipes M, Eisenbarth G, et al. Transgenic insulin (B:9-23) T-cell receptor mice develop autoimmune diabetes dependent upon RAG genotype, H-2g7 homozygosity, and insulin 2 gene knockout. Diabetes. 2006;55:1978-84 pubmed
    ..for H-2(g7), the presence of additional T-/B-cell receptor-rearranged genes (RAG(+) versus RAG(-/-)), and the insulin 2 gene knockout (the insulin gene expressed in the NOD thymus). Despite lymphopenia, 40% of H-2(g7/g7) BDC12-4...
  14. Kopp J, Dubois C, Schaffer A, Hao E, Shih H, Seymour P, et al. Sox9+ ductal cells are multipotent progenitors throughout development but do not produce new endocrine cells in the normal or injured adult pancreas. Development. 2011;138:653-65 pubmed publisher
  15. Zito E, Chin K, Blais J, Harding H, Ron D. ERO1-beta, a pancreas-specific disulfide oxidase, promotes insulin biogenesis and glucose homeostasis. J Cell Biol. 2010;188:821-32 pubmed publisher
    ..in this study that homozygosity for a disrupting allele of Ero1lb selectively compromises oxidative folding of proinsulin and promotes glucose intolerance in mutant mice...
  16. Morris S, Gao T, Cooper T, Kepka Lenhart D, Awad A. Arginase-2 mediates diabetic renal injury. Diabetes. 2011;60:3015-22 pubmed publisher
    ..To determine 1) whether renal arginase activity or expression is increased in diabetes and 2) whether arginase plays a role in development of diabetic nephropathy (DN)...
  17. Krause M, Moradi J, Nissar A, Riddell M, Hawke T. Inhibition of plasminogen activator inhibitor-1 restores skeletal muscle regeneration in untreated type 1 diabetic mice. Diabetes. 2011;60:1964-72 pubmed publisher
    ..With the use of Ins2(WT/C96Y) mice (model of adolescent-onset type 1 diabetes), muscle regeneration was characterized in terms of muscle ..
  18. Lo C, Chang S, Chenier I, Filep J, Ingelfinger J, Zhang S, et al. Heterogeneous nuclear ribonucleoprotein F suppresses angiotensinogen gene expression and attenuates hypertension and kidney injury in diabetic mice. Diabetes. 2012;61:2597-608 pubmed
    ..The underlying mechanism is mediated, at least in part, via the suppression of intrarenal Agt gene expression in vivo. hnRNP F may be a potential target in the treatment of hypertension and kidney injury in diabetes...
  19. Gannon M, Ables E, Crawford L, Lowe D, OFFIELD M, Magnuson M, et al. pdx-1 function is specifically required in embryonic beta cells to generate appropriate numbers of endocrine cell types and maintain glucose homeostasis. Dev Biol. 2008;314:406-17 pubmed
  20. Doyle M, Loomis Z, Sussel L. Nkx2.2-repressor activity is sufficient to specify alpha-cells and a small number of beta-cells in the pancreatic islet. Development. 2007;134:515-23 pubmed
    ..2 through its TN domain. These studies suggest that Nkx2.2 functions predominantly as a transcriptional repressor during specification of endocrine cell types in the pancreas. ..
  21. Kakoki M, Kizer C, Yi X, Takahashi N, Kim H, Bagnell C, et al. Senescence-associated phenotypes in Akita diabetic mice are enhanced by absence of bradykinin B2 receptors. J Clin Invest. 2006;116:1302-9 pubmed
    ..in B2 receptor-null mice, clearly apparent in mice diabetic because of a dominant mutation (Akita) in the Ins2 gene, and most obvious in Akita diabetic plus B2 receptor-null mice...
  22. Seymour P, Freude K, Dubois C, Shih H, Patel N, Sander M. A dosage-dependent requirement for Sox9 in pancreatic endocrine cell formation. Dev Biol. 2008;323:19-30 pubmed publisher
    ..Our findings therefore suggest that defective endocrine specification might underlie the pancreatic phenotype of individuals with CD. ..
  23. Herbach N, Rathkolb B, Kemter E, Pichl L, Klaften M, de Angelis M, et al. Dominant-negative effects of a novel mutated Ins2 allele causes early-onset diabetes and severe beta-cell loss in Munich Ins2C95S mutant mice. Diabetes. 2007;56:1268-76 pubmed
    ..These mice exhibit a T-->A transversion in the insulin 2 (Ins2) gene at nucleotide position 1903 in exon 3, which leads to the amino acid exchange C95S and loss of the ..
  24. Nakamura K, Minami K, Tamura K, Iemoto K, Miki T, Seino S. Pancreatic ?-cells are generated by neogenesis from non-?-cells after birth. Biomed Res. 2011;32:167-74 pubmed
    ..Here, we address this issue by using the inducible Cre/loxP system to trace ?-cells. We generated Ins2-CreERT2/R26R-YFP double knock-in mice, in which pancreatic ?-cells can be labeled specifically and permanently upon ..
  25. Vuguin P, Kedees M, Cui L, Guz Y, Gelling R, Nejathaim M, et al. Ablation of the glucagon receptor gene increases fetal lethality and produces alterations in islet development and maturation. Endocrinology. 2006;147:3995-4006 pubmed
    ..These findings suggest that GLU participates in a feedback loop that regulates the proportion of the different endocrine cell types in islets, the number of islets per pancreas, and development of the mature alpha-cell phenotype. ..
  26. Oudit G, Liu G, Zhong J, Basu R, Chow F, Zhou J, et al. Human recombinant ACE2 reduces the progression of diabetic nephropathy. Diabetes. 2010;59:529-38 pubmed publisher
    ..Male 12-week-old diabetic Akita mice (Ins2(WT/C96Y)) and control C57BL/6J mice (Ins2(WT/WT)) were injected daily with placebo or with rhACE2 (2 mg/kg, i.p...
  27. Anderson K, Torres C, Solomon K, Becker T, Newgard C, Wright C, et al. Cooperative transcriptional regulation of the essential pancreatic islet gene NeuroD1 (beta2) by Nkx2.2 and neurogenin 3. J Biol Chem. 2009;284:31236-48 pubmed publisher
    ..Collectively, these findings further define the conserved regulatory networks involved in islet beta cell formation and function. ..
  28. Hodish I, Absood A, Liu L, Liu M, Haataja L, Larkin D, et al. In vivo misfolding of proinsulin below the threshold of frank diabetes. Diabetes. 2011;60:2092-101 pubmed publisher
    ..Herein we have compared two mouse models expressing equally small amounts of transgenic proinsulin in pancreatic ?-cells...
  29. Schaffer A, Taylor B, Benthuysen J, Liu J, Thorel F, Yuan W, et al. Nkx6.1 controls a gene regulatory network required for establishing and maintaining pancreatic Beta cell identity. PLoS Genet. 2013;9:e1003274 pubmed publisher
    ..Given the lack of Nkx6.1 expression and aberrant activation of non-beta endocrine hormones in human embryonic stem cell (hESC)-derived insulin(+) cells, our study has significant implications for developing cell replacement therapies. ..
  30. Mohan J, Petzold S, Unanue E. Register shifting of an insulin peptide-MHC complex allows diabetogenic T cells to escape thymic deletion. J Exp Med. 2011;208:2375-83 pubmed publisher
    ..Thus, self-reactive T cells can become pathogenic in the target organ where high concentrations of antigen and/or differences in intracellular processing present peptides in registers distinct from those found in the thymus. ..
  31. Yang Y, Thorel F, Boyer D, Herrera P, Wright C. Context-specific ?- to-?-cell reprogramming by forced Pdx1 expression. Genes Dev. 2011;25:1680-5 pubmed publisher
    ..Our findings reveal that Pdx1 can work single-handedly as a potent context-dependent autonomous reprogramming agent, and suggest a postnatal differentiation evaluation stage involved in normal endocrine maturation. ..
  32. Hombrebueno J, Chen M, Peñalva R, Xu H. Loss of synaptic connectivity, particularly in second order neurons is a key feature of diabetic retinal neuropathy in the Ins2Akita mouse. PLoS ONE. 2014;9:e97970 pubmed publisher
    ..Our findings suggest that the Ins2Akita mouse is a good model to study diabetic retinal neuropathy. ..
  33. Du A, Hunter C, Murray J, Noble D, Cai C, Evans S, et al. Islet-1 is required for the maturation, proliferation, and survival of the endocrine pancreas. Diabetes. 2009;58:2059-69 pubmed publisher
    ..These results demonstrate the requirement for Isl-1 in the maturation, proliferation, and survival of the second wave of hormone-producing islet cells. ..
  34. Hong E, Jung D, Ko H, Zhang Z, Ma Z, Jun J, et al. Nonobese, insulin-deficient Ins2Akita mice develop type 2 diabetes phenotypes including insulin resistance and cardiac remodeling. Am J Physiol Endocrinol Metab. 2007;293:E1687-96 pubmed
    ..A point mutation of insulin 2 gene in Ins2(Akita) mice leads to pancreatic beta-cell apoptosis and hyperglycemia, and these mice are commonly ..
  35. Wong D, Oudit G, Reich H, Kassiri Z, Zhou J, Liu Q, et al. Loss of angiotensin-converting enzyme-2 (Ace2) accelerates diabetic kidney injury. Am J Pathol. 2007;171:438-51 pubmed
    ..Ace2(-/-) mice were crossed with Akita mice (Ins2(WT/C96Y)), a model of type 1 diabetes mellitus, and four groups of mice were studied at 3 months of age: Ace2(+/y)..
  36. Oyadomari S, Yun C, Fisher E, Kreglinger N, Kreibich G, Oyadomari M, et al. Cotranslocational degradation protects the stressed endoplasmic reticulum from protein overload. Cell. 2006;126:727-39 pubmed
    ..Thus, P58(IPK) is a key mediator of cotranslocational ER protein degradation, and this process likely contributes to ER homeostasis in stressed cells. ..
  37. Murray A, Chen Q, Takahashi Y, Zhou K, Park K, Ma J. MicroRNA-200b downregulates oxidation resistance 1 (Oxr1) expression in the retina of type 1 diabetes model. Invest Ophthalmol Vis Sci. 2013;54:1689-97 pubmed publisher
    ..Here, we identified miRNA expression changes in the retinas of Akita mice, a genetic model of type 1 diabetes, and investigated the potential role of miRNA in diabetic retinopathy...
  38. Mochida T, Tanaka T, Shiraki Y, Tajiri H, Matsumoto S, Shimbo K, et al. Time-dependent changes in the plasma amino acid concentration in diabetes mellitus. Mol Genet Metab. 2011;103:406-9 pubmed publisher
    ..We show that the degree and timing of the changes were different among the plasma amino acid concentrations (pAAs) during the development of type 1 DM. ..
  39. Mastracci T, Wilcox C, Arnés L, Panea C, Golden J, MAY C, et al. Nkx2.2 and Arx genetically interact to regulate pancreatic endocrine cell development and endocrine hormone expression. Dev Biol. 2011;359:1-11 pubmed publisher
    ..Together, these experiments identify novel genetic interactions between Nkx2.2 and Arx within the endocrine progenitor cells that ensure the correct specification and regulation of endocrine hormone-producing cells. ..
  40. Burlison J, Long Q, Fujitani Y, Wright C, Magnuson M. Pdx-1 and Ptf1a concurrently determine fate specification of pancreatic multipotent progenitor cells. Dev Biol. 2008;316:74-86 pubmed publisher
    ..Taken together, these studies indicate that Pdx-1 and Ptf1a have distinct but interdependent functions during pancreatic MPC specification. ..
  41. Magenheim J, Ilovich O, Lazarus A, Klochendler A, Ziv O, Werman R, et al. Blood vessels restrain pancreas branching, differentiation and growth. Development. 2011;138:4743-52 pubmed publisher
    ..The effects are seen both in vivo and ex vivo, indicating a perfusion-independent mechanism. Thus, the vasculature controls pancreas morphogenesis and growth by reducing branching and differentiation of primitive epithelial cells. ..
  42. Xuan S, Borok M, Decker K, Battle M, Duncan S, Hale M, et al. Pancreas-specific deletion of mouse Gata4 and Gata6 causes pancreatic agenesis. J Clin Invest. 2012;122:3516-28 pubmed publisher
  43. Han Z, Guo J, Conley S, Naash M. Retinal angiogenesis in the Ins2(Akita) mouse model of diabetic retinopathy. Invest Ophthalmol Vis Sci. 2013;54:574-84 pubmed publisher
    ..Although chemical- and injury-induced models of retinal neovascularization exist, the need for a genetic model that closely simulates the DR pathologic process is great...
  44. Juhl K, Sarkar S, Wong R, Jensen J, Hutton J. Mouse pancreatic endocrine cell transcriptome defined in the embryonic Ngn3-null mouse. Diabetes. 2008;57:2755-61 pubmed publisher
    ..The deposited data provide a rich resource that can be used to address diverse questions related to islet developmental and cell biology and the pathogenesis of type 1 and 2 diabetes. ..
  45. Nishimura W, Kondo T, Salameh T, El Khattabi I, Dodge R, Bonner Weir S, et al. A switch from MafB to MafA expression accompanies differentiation to pancreatic beta-cells. Dev Biol. 2006;293:526-39 pubmed
    ..Thus, this redundancy in the function and expression of the large-Maf factors may explain the normal islet morphology observed in the MafA knockout mice at birth. ..
  46. Desgraz R, Herrera P. Pancreatic neurogenin 3-expressing cells are unipotent islet precursors. Development. 2009;136:3567-74 pubmed publisher
    ..We propose a model whereby Ngn3(+) cells are monotypic (i.e. unipotent) precursors, and use this paradigm to refocus ideas on how cell number and type must be regulated in building complete islets of Langerhans. ..
  47. Kim S, Rane S. The Cdk4-E2f1 pathway regulates early pancreas development by targeting Pdx1+ progenitors and Ngn3+ endocrine precursors. Development. 2011;138:1903-12 pubmed publisher
  48. Gastinger M, Singh R, Barber A. Loss of cholinergic and dopaminergic amacrine cells in streptozotocin-diabetic rat and Ins2Akita-diabetic mouse retinas. Invest Ophthalmol Vis Sci. 2006;47:3143-50 pubmed
    ..Whole retinas from streptozotocin (STZ)-diabetic rats and Ins2(Akita) mice were fixed in paraformaldehyde...
  49. Babaya N, Nakayama M, Moriyama H, Gianani R, Still T, Miao D, et al. A new model of insulin-deficient diabetes: male NOD mice with a single copy of Ins1 and no Ins2. Diabetologia. 2006;49:1222-8 pubmed
    ..a single copy of Ins2 (NOD( Ins1-/-,Ins2+/-)) and NOD( Ins1+/-,Ins2-/-) mice with a transgene encoding B16:Ala proinsulin. By 10 weeks of age, all male NOD( Ins1+/-,Ins2-/-) mice were diabetic, whereas all female NOD( Ins1+/-,Ins2-/-) ..
  50. Pfister F, Feng Y, Vom Hagen F, Hoffmann S, Molema G, Hillebrands J, et al. Pericyte migration: a novel mechanism of pericyte loss in experimental diabetic retinopathy. Diabetes. 2008;57:2495-502 pubmed publisher
    ..Diabetic pericyte loss is the result of pericyte migration, and this process is modulated by the Ang-Tie system. ..
  51. Kordowich S, Collombat P, Mansouri A, Serup P. Arx and Nkx2.2 compound deficiency redirects pancreatic alpha- and beta-cell differentiation to a somatostatin/ghrelin co-expressing cell lineage. BMC Dev Biol. 2011;11:52 pubmed publisher
    ..Our analysis also suggests that one of the coupled functions of Nkx2.2 and Pax4 is to counteract Arx gene activity in early committed beta-cells. ..
  52. Nakayama M, Beilke J, Jasinski J, Kobayashi M, Miao D, Li M, et al. Priming and effector dependence on insulin B:9-23 peptide in NOD islet autoimmunity. J Clin Invest. 2007;117:1835-43 pubmed
    NOD mice with knockout of both native insulin genes and a mutated proinsulin transgene, alanine at position B16 in preproinsulin (B16:A-dKO mice), do not develop diabetes...
  53. Salem E, Grobe N, Elased K. Insulin treatment attenuates renal ADAM17 and ACE2 shedding in diabetic Akita mice. Am J Physiol Renal Physiol. 2014;306:F629-39 pubmed publisher
    ..Urinary ACE2 could be used as a biomarker for diabetic nephropathy and as an index of intrarenal ACE2 status. ..
  54. Carbe C, Hertzler Schaefer K, Zhang X. The functional role of the Meis/Prep-binding elements in Pax6 locus during pancreas and eye development. Dev Biol. 2012;363:320-9 pubmed publisher
    ..Together, these results provide functional evidence for the independent and synergistic roles of the Pax6 upstream enhancers, and they suggest the potential redundancy of Meis/Prep protein in Pax6 regulation...
  55. Nir T, Melton D, Dor Y. Recovery from diabetes in mice by beta cell regeneration. J Clin Invest. 2007;117:2553-61 pubmed
    ..These results suggest that regenerative therapy for type 1 diabetes may be achieved if autoimmunity is halted using regeneration-compatible drugs. ..
  56. Magnuson M, Osipovich A. Pancreas-specific Cre driver lines and considerations for their prudent use. Cell Metab. 2013;18:9-20 pubmed publisher
    ..We also discuss preferred strategies for achieving high-fidelity driver lines and remind investigators of the continuing need for caution when interpreting results obtained from any Cre/LoxP-based experiment performed in mice. ..
  57. Wang C, Li F, Hiller S, Kim H, Maeda N, Smithies O, et al. A modest decrease in endothelial NOS in mice comparable to that associated with human NOS3 variants exacerbates diabetic nephropathy. Proc Natl Acad Sci U S A. 2011;108:2070-5 pubmed publisher
    ..inbred females and heterozygous C57BL/6J eNOS(+/-) inbred males carrying the dominant Akita diabetogenic mutation Ins2(C96Y/+)...
  58. Wang S, Jensen J, Seymour P, Hsu W, Dor Y, Sander M, et al. Sustained Neurog3 expression in hormone-expressing islet cells is required for endocrine maturation and function. Proc Natl Acad Sci U S A. 2009;106:9715-20 pubmed publisher
    ..These findings demonstrate that Neurog3 is required not only for initiating endocrine cell differentiation, but also for promoting islet cell maturation and maintaining islet function. ..
  59. Smith S, Duplantier J, Dun Y, Mysona B, Roon P, Martin P, et al. In vivo protection against retinal neurodegeneration by sigma receptor 1 ligand (+)-pentazocine. Invest Ophthalmol Vis Sci. 2008;49:4154-61 pubmed publisher
    ..Spontaneously diabetic Ins2(Akita/+) and wild-type mice received intraperitoneal injections of (+)-pentazocine for 22 weeks beginning at ..
  60. Mellitzer G, Beucher A, Lobstein V, Michel P, Robine S, Kedinger M, et al. Loss of enteroendocrine cells in mice alters lipid absorption and glucose homeostasis and impairs postnatal survival. J Clin Invest. 2010;120:1708-21 pubmed publisher
    ..Our data help unravel the role of enteroendocrine cells and hormones in lipid absorption and maintenance of the intestinal epithelium. ..
  61. 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
    ..regions of the preproinsulin molecule, and we predict that they prevent normal folding and progression of proinsulin in the insulin secretory pathway...
  62. Bugger H, Chen D, Riehle C, Soto J, Theobald H, Hu X, et al. Tissue-specific remodeling of the mitochondrial proteome in type 1 diabetic akita mice. Diabetes. 2009;58:1986-97 pubmed publisher
    ..Preservation of mitochondrial function in kidney, brain, and liver, versus mitochondrial dysfunction in the heart, supports a central role for mitochondrial dysfunction in diabetic cardiomyopathy. ..
  63. Xu Y, Wang S, Zhang J, Zhao A, Stanger B, Gu G. The fringe molecules induce endocrine differentiation in embryonic endoderm by activating cMyt1/cMyt3. Dev Biol. 2006;297:340-9 pubmed
    ..These results suggest that Mfng-mediated repression of Notch signaling could serve as a trigger for endocrine islet differentiation. ..
  64. Nishimura W, Rowan S, Salameh T, Maas R, Bonner Weir S, Sell S, et al. Preferential reduction of beta cells derived from Pax6-MafB pathway in MafB deficient mice. Dev Biol. 2008;314:443-56 pubmed publisher
    ..Thus, Pax6 acts upstream of MafB, which in turn may trigger the expression of insulin and regulate the PDX-1 and MafA expression required for beta-cell maturation. ..
  65. Gupta S, McGrath B, Cavener D. PERK (EIF2AK3) regulates proinsulin trafficking and quality control in the secretory pathway. Diabetes. 2010;59:1937-47 pubmed publisher
    ..abnormal cellular phenotype characterized by grossly distended endoplasmic reticulum (ER) and retention of proinsulin. We investigated over synthesis, lack of ER-associated degradation (ERAD), and defects in ER to Golgi ..
  66. Nelson S, Schaffer A, Sander M. The transcription factors Nkx6.1 and Nkx6.2 possess equivalent activities in promoting beta-cell fate specification in Pdx1+ pancreatic progenitor cells. Development. 2007;134:2491-500 pubmed
    ..2 in endocrine differentiation are a consequence of their divergent spatiotemporal expression domains rather than their biochemical activities and implies that both Nkx6.1 and Nkx6.2 possess alpha- and beta-cell-specifying activities. ..
  67. Liu J, Hunter C, Du A, Ediger B, Walp E, Murray J, et al. Islet-1 regulates Arx transcription during pancreatic islet alpha-cell development. J Biol Chem. 2011;286:15352-60 pubmed publisher
    ..Isl-1 represents the first known activator of Arx transcription in ?-cells, here established to be acting through the conserved Re1 and Re2 control domains. ..
  68. Shiao M, Liao B, Long M, Yu H. Adaptive evolution of the insulin two-gene system in mouse. Genetics. 2008;178:1683-91 pubmed publisher
    ..genes in mouse and rat compose a two-gene system in which Ins1 was retroposed from the partially processed mRNA of Ins2. When Ins1 originated and how it was retained in genomes still remain interesting problems...
  69. Dubois C, Shih H, Seymour P, Patel N, Behrmann J, Ngo V, et al. Sox9-haploinsufficiency causes glucose intolerance in mice. PLoS ONE. 2011;6:e23131 pubmed publisher
    ..Moreover, our analysis revealed a novel role for Sox9 in maintaining the expression of Pdx1/MODY4, which is an important transcriptional regulator of beta-cell development...
  70. Kilic G, Wang J, Sosa Pineda B. Osteopontin is a novel marker of pancreatic ductal tissues and of undifferentiated pancreatic precursors in mice. Dev Dyn. 2006;235:1659-67 pubmed
    ..Finally, the maintenance of Opn expression in pancreatic tissues of adults argues for a possible function of this protein in injury and pathologic responses. ..
  71. Wang Q, Elghazi L, Martin S, Martins I, Srinivasan R, Geng X, et al. Ghrelin is a novel target of Pax4 in endocrine progenitors of the pancreas and duodenum. Dev Dyn. 2008;237:51-61 pubmed
    ..Together, our data further support the notion that Pax4 activity is necessary to establish appropriate patterns of gene expression in endocrine progenitors of the digestive tract. ..
  72. Wang S, Zhang J, Zhao A, Hipkens S, Magnuson M, Gu G. Loss of Myt1 function partially compromises endocrine islet cell differentiation and pancreatic physiological function in the mouse. Mech Dev. 2007;124:898-910 pubmed
    ..The consequences of Myt1 inactivation in the developing pancreas could be masked by activation of its paralogs, Myt1l and Myt3. These findings suggest Myt1 is involved in proper endocrine differentiation and function. ..
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    ..These studies demonstrate a unique position for Rfx6 in the hierarchy of factors that coordinate pancreatic islet development in both mice and humans. Rfx6 could prove useful in efforts to generate beta-cells for patients with diabetes. ..
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    ..The control of Neurog3+ cell number and the Neurog3 threshold-dependent endocrine differentiation mechanism combine to select a specific proportion of pancreatic progenitor cells to adopt the islet cell fate. ..
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    ..Recently, we have found proinsulin is an aggregation-prone molecule inherent with a low relative folding rate and maintains a homeostatic balance ..
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    ..By contrast, beta cells, whose number is only slightly reduced, were no longer clustered in a compact islet. These data unveil Rfx6 as a novel regulator of islet cell development. ..