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- W1965356948 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." @default.
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- W1965356948 date "2011-11-01" @default.
- W1965356948 modified "2023-10-18" @default.
- W1965356948 title "Contribution of Different Mechanisms to Pancreatic Beta-cell Hyper-secretion in Non-obese Diabetic (NOD) Mice during Pre-diabetes" @default.
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- W1965356948 doi "https://doi.org/10.1074/jbc.m111.295931" @default.
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