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Publication : Novel murine model of congenital diabetes: The insulin hyposecretion mouse.

First Author  Nakano K Year  2019
Journal  J Diabetes Investig Volume  10
Issue  2 Pages  227-237
PubMed ID  29987871 Mgi Jnum  J:290011
Mgi Id  MGI:6441105 Doi  10.1111/jdi.12895
Citation  Nakano K, et al. (2019) Novel murine model of congenital diabetes: The insulin hyposecretion mouse. J Diabetes Investig 10(2):227-237
abstractText  AIMS/INTRODUCTION: Diabetic animal models have made an enormous contribution to our understanding of the etiology of diabetes and the development of new medications. The aim of the present study was to develop and characterize a novel, non-obese murine strain with spontaneous diabetes - the insulin hyposecretion (ihs) mouse. MATERIALS AND METHODS: During the development of the ICGN.B6-Tns2(WT) strain as the control for the ICGN-Tns2(nph) congenital nephrotic strain, diabetic mice were discovered and named ihs mice. Intraperitoneal insulin tolerance test, oral glucose tolerance test and an insulin secretion experiment by the pancreas perfusion system were carried out on ihs mice. The pancreatic islets were examined histologically, and the mRNA expression of pancreatic beta-cell-specific genes or genes associated with monogenic diabetes was examined by RT-qPCR. RESULTS: The ihs mice showed several distinctive diabetes-related characteristics: (i) the onset of diabetes was observed only in the male mice; (ii) there were no differences in insulin content between the ihs and control mice; (iii) impaired insulin secretion was elicited by glucose, potassium chloride and sulfonylureas; (iv) there was a significant reduction of relative beta-cell volume with no signs of inflammation or fibrosis; (v) they showed a normal glycemic response to exogenous insulin; and (vi) the mice were not obese. CONCLUSIONS: The ihs mouse provides a novel murine model of congenital diabetes that shows insulin secretion failure. This model allows not only an analysis of the progression of diabetes, but also the identification of unknown genes involved in insulin secretion.
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