First Author | Li Q | Year | 2017 |
Journal | Endocrinology | Volume | 158 |
Issue | 6 | Pages | 1634-1644 |
PubMed ID | 28009527 | Mgi Jnum | J:246085 |
Mgi Id | MGI:5918384 | Doi | 10.1210/en.2016-1551 |
Citation | Li Q, et al. (2017) Reg2 Expression Is Required for Pancreatic Islet Compensation in Response to Aging and High-Fat Diet-Induced Obesity. Endocrinology 158(6):1634-1644 |
abstractText | Maintaining pancreatic beta-cell mass and function is essential for normal insulin production and glucose homeostasis. Regenerating islet-derived 2 (Reg2, Reg II, human ortholog Reg1B) gene is normally expressed in pancreatic acinar cells and is significantly induced in response to diabetes, pancreatitis, and high-fat diet (HFD) and during pancreatic regeneration. To evaluate the role of endogenous Reg2 production in normal beta-cell function, we characterized Reg2 gene-deficient (Reg2-/-) mice under normal conditions and when subjected to several pathological challenges. At a young age, Reg2 gene deficiency caused no obvious change in normal islet morphology or glucose tolerance. There was no change in the severity of streptozotocin-induced diabetes or caerulein-induced acute pancreatitis in the Reg2-/- mice, indicating that the increased Reg2 expression under those conditions was not essential to protect the islet or acinar cells. However, 13- to 14-month-old Reg2-/- mice developed glucose intolerance associated with significantly decreased islet beta-cell ratio and serum insulin level. Similarly, after young mice were fed an HFD for 19 weeks, diminished islet mass expansion and serum insulin level were observed in Reg2-/- vs wild-type mice. This was associated with a decline in the rate of individual beta-cell proliferation measured by Ki67 labeling. In both conditions, the beta-cells were smaller in gene-deficient vs wild-type mice. Our results indicate that normal expression of Reg2 gene is required for appropriate compensations in pancreatic islet proliferation and expansion in response to obesity and aging. |