title: Contribution of different mechanisms to pancreatic beta-cell hyper-secretion in non-obese diabetic (NOD) mice during pre-diabetes.
abstract: The development of insulin-dependent diabetes mellitus (IDDM) results from the selective destruction of pancreatic beta-cells. Both humans and spontaneous models of IDDM, such as NOD mice, have an extended pre-diabetic stage. Dynamic changes in beta-cell mass and function during pre-diabetes, such as insulin hyper-secretion, remain largely unknown. In this paper, we evaluated pre-diabetic female NOD mice at different ages (6, 10, and 14 weeks old) to illustrate alterations in beta-cell mass and function as disease progressed. We found an increase in beta-cell mass in 6-week-old NOD mice that may account for improved glucose tolerance in these mice. As NOD mice aged, beta-cell mass progressively reduced with increasing insulitis. In parallel, secretory ability of individual beta-cells was enhanced due to an increase in the size of slowly releasable pool (SRP) of vesicles. Moreover, expression of both SERCA2 and SERCA3 genes were progressively down-regulated, which facilitated depolarization-evoked secretion by prolonging Ca(2+) elevation upon glucose stimulation. In summary, we propose that different mechanisms contribute to the insulin hyper-secretion at different ages of pre-diabetic NOD mice, which may provide some new ideas concerning the progression and management of type I diabetes.
authors.affiliation: Department of General Surgery, XuanWu Hospital, Capital Medical University, Beijing, 100053, PR China.
authors.forename: Kuo
authors.initials: K
authors.lastname: Liang
authors.forename: Wen
authors.initials: W
authors.lastname: Du
authors.forename: Wenzhen
authors.initials: W
authors.lastname: Zhu
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.forename: Yeqing
authors.initials: Y
authors.lastname: Cui
authors.forename: Haichen
authors.initials: H
authors.lastname: Sun
authors.forename: Bin
authors.initials: B
authors.lastname: Luo
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Xue
authors.forename: Lu
authors.initials: L
authors.lastname: Yang
authors.forename: Liangyi
authors.initials: L
authors.lastname: Chen
authors.forename: Fei
authors.initials: F
authors.lastname: Li
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D048429:Cell Size; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000096:biosynthesis; D013549:Sweetening Agents / Q000494:pharmacology
chemical_list: D007328:Insulin; D013549:Sweetening Agents; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506947:Atp2a2 protein, mouse; C506950:Atp2a3 protein, mouse; D005947:Glucose