Calbindin-D9k Ablation Disrupt Glucose-Pancreatic Insulin HomeostasisReport as inadecuate

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It has been proposed that cellular Ca2+ signals activate hormone secretion. In pancreatic β cells, which produce insulin, Ca2+ signals have been known to contribute to insulin secretion. Prior to this study, we confirmed that insulin-secreting β cells express CaBP-9k, and assumed that CaBP-9k play a role in β cell insulin synthesis or secretion. Using CaBP-9k knock out KO mice, we demonstrated that ablation of CaBP-9k causes reducing insulin secretion and increasing serum glucose. To compare the role of CaBP-9k with pathophysiological conditions, we exposed wild-type and CaBP-9k KO mice to hypoxic conditions for 10 days. Hypoxia induced endoplasmic reticulum ER stress, increasing both insulin signaling and insulin resistance. By exposing hypoxia, CaBP-9k KO mice showed an increased level of ER stress marker protein relative to wild type mice. Without hypoxic conditions, CaBP-9K ablation regulates calcium channels and causes ER stress in a CaBP-9K specific manner. Ablation of CaBP-9k also showed decreased levels of sulfonylurea receptor1 SUR1 and inward-rectifier potassium ion channel 6.2 Kir6.2, which are insulin secretion marker genes. Overall, the results of the present study demonstrated that CaBP-9k regulates synthesis of insulin and is part of the insulin-secreting calcium signaling.

Author: Changhwan Ahn, Dongoh Lee, Jae-Hwan Lee, Hyun Yang, Beum-Soo An, Eui-Bae Jeung



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