title: Loss of β-arrestin2 mediates pancreatic-islet dysfunction in mice.
abstract: Insulin resistance and defective insulin secretion are two major factors contributing to the pathogenesis of type 2 diabetes. β-Arrestin2 is known to interact with numerous signaling molecules. Our previous study demonstrated that β-arrestin2 regulates insulin sensitivity in both skeletal muscle and liver, yet its role in insulin secretion remains elusive. In this study, we found that β-arrestin2 was abundantly expressed in mouse pancreatic beta cells, while its expression was significantly decreased in obese and diabetic mouse models. Hyperglycemic clamp study showed that the acute and late phase of insulin secretion were impaired in β-arrestin2 knockout mice. Ex vivo study showed that β-arrestin2 deficient pancreatic islets exhibited blunted glucose-stimulated insulin secretion. Further analysis demonstrated the number of docked insulin granules in β-arrestin2 deficient islets was markedly decreased compared to wild-type islets, while insulin content and beta cell mass remained unchanged. Our study establishes a new role for β-arrestin2 in beta-cell functions, and suggests that the down regulation of β-arrestin2 may contribute to impaired insulin secretion in type 2 diabetes.
authors: Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China.
authors: Mingliang
authors: M
authors: Zhang
authors: Yunxia
authors: Y
authors: Zhu
authors: Kaida
authors: K
authors: Mu
authors: Ling
authors: L
authors: Li
authors: Junxi
authors: J
authors: Lu
authors: Jian
authors: J
authors: Zhao
authors: Xinyi
authors: X
authors: Huang
authors: Chen
authors: C
authors: Wang
authors: Weiping
authors: W
authors: Jia
mesh_terms: D000818:Animals; D019390:Arrestins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000473:pathology* / Q000502:physiology*; D007515:Islets of Langerhans / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008820:Mice, Obese; D009765:Obesity / Q000473:pathology / Q000503:physiopathology; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D007328:Insulin; D000071557:beta-Arrestins