Laboratory of Laboratory Animal Science and Medicine, School of Veterinary Medicine, Kitasato University, Towada, Japan.
Department of Laboratory Animal Medicine, Research Institute, National Center for Global Health and Medicine (NCGM), Tokyo, Japan.
J Diabetes Investig. 2019 Mar;10(2):227-237. doi: 10.1111/jdi.12895. Epub 2018 Aug 17.
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.
During the development of the ICGN.B6-Tns2 strain as the control for the ICGN-Tns2 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 β-cell-specific genes or genes associated with monogenic diabetes was examined by RT-qPCR.
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 β-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.
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.
目的/引言：糖尿病动物模型为我们理解糖尿病的病因和开发新药物做出了巨大贡献。本研究旨在开发和鉴定一种新型的自发性糖尿病非肥胖小鼠品系——胰岛素分泌不足（ihs）小鼠。
在 ICGN.B6-Tns2 品系的开发过程中，作为 ICGN-Tns2 先天性肾病品系的对照，我们发现了糖尿病小鼠，并将其命名为 ihs 小鼠。对 ihs 小鼠进行了腹腔内胰岛素耐量试验、口服葡萄糖耐量试验和胰腺灌流系统的胰岛素分泌试验。对胰岛进行了组织学检查，并通过 RT-qPCR 检查了胰腺 β 细胞特异性基因或与单基因糖尿病相关基因的 mRNA 表达。
ihs 小鼠表现出几种与糖尿病相关的特征：（i）糖尿病仅在雄性小鼠中出现；（ii）ihs 小鼠和对照小鼠的胰岛素含量无差异；（iii）葡萄糖、氯化钾和磺酰脲类药物刺激下胰岛素分泌受损；（iv）相对β细胞体积明显减少，无炎症或纤维化迹象；（v）对外源胰岛素有正常的血糖反应；（vi）小鼠不肥胖。
ihs 小鼠提供了一种新的先天性糖尿病小鼠模型，表现为胰岛素分泌衰竭。该模型不仅允许分析糖尿病的进展，还允许鉴定未知的参与胰岛素分泌的基因。
