title: Reg2 Expression Is Required for Pancreatic Islet Compensation in Response to Aging and High-Fat Diet-Induced Obesity.
abstract: Maintaining pancreatic β-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 β-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 β-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 β-cell proliferation measured by Ki67 labeling. In both conditions, the β-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.
authors.affiliation: Fraser Laboratories for Diabetes Research, Department of Medicine, McGill University Health Centre, Montreal, Quebec H4A 3J1, Canada.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Fraser Laboratories for Diabetes Research, Department of Medicine, McGill University Health Centre, Montreal, Quebec H4A 3J1, Canada.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu 21009, China.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Miao
authors.affiliation: Fraser Laboratories for Diabetes Research, Department of Medicine, McGill University Health Centre, Montreal, Quebec H4A 3J1, Canada.
authors.forename: Christopher
authors.initials: C
authors.lastname: Ramgattie
authors.affiliation: Department of Pathology, McGill University Health Centre, Montreal, Quebec H4A 3J1, Canada.
authors.forename: Zu-Hua
authors.initials: ZH
authors.lastname: Gao
authors.affiliation: Fraser Laboratories for Diabetes Research, Department of Medicine, McGill University Health Centre, Montreal, Quebec H4A 3J1, Canada.|Montreal Diabetes Research Centre, Montreal, Quebec H2X 0A9, Canada.
authors.forename: Jun-Li
authors.initials: JL
authors.lastname: Liu
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D015870:Gene Expression; D050417:Insulin-Secreting Cells / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins / Q000235:genetics*
chemical_list: D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; C490253:Reg3b protein, mouse