title: Calbindin-D9k Ablation Disrupt Glucose/Pancreatic Insulin Homeostasis.
abstract: 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.
authors.affiliation: Laboratory of Veterinary Biochemistry and Molecular Biology, Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.
authors.forename: Changhwan
authors.initials: C
authors.lastname: Ahn
authors.affiliation: Laboratory of Veterinary Biochemistry and Molecular Biology, Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.
authors.forename: Dongoh
authors.initials: D
authors.lastname: Lee
authors.affiliation: Laboratory of Veterinary Biochemistry and Molecular Biology, Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.
authors.forename: Jae-Hwan
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Laboratory of Veterinary Biochemistry and Molecular Biology, Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Biomaterials Science, College of National Resources & Life Science, Pusan National University, Miryang, Gyeongsangnam-do 627-706, Republic of Korea.
authors.forename: Beum-Soo
authors.initials: BS
authors.lastname: An
authors.affiliation: Laboratory of Veterinary Biochemistry and Molecular Biology, Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.
authors.forename: Eui-Bae
authors.identifier: http://orcid.org/0000-0001-8936-916X
authors.initials: EB
authors.lastname: Jeung
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001786:Blood Glucose / Q000032:analysis*; D064026:Calbindins / Q000172:deficiency / Q000235:genetics*; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress; D005951:Glucose Tolerance Test; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D000860:Hypoxia; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism; D064233:Sulfonylurea Receptors / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D000099161:Kcnj11 Channel
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D001786:Blood Glucose; D064026:Calbindins; D002118:Calcium; D018398:Homeodomain Proteins; D007328:Insulin; D024661:Potassium Channels, Inwardly Rectifying; D064233:Sulfonylurea Receptors; D015534:Trans-Activators; D000099161:Kcnj11 Channel; C501008:Neurod1 protein, mouse; C084010:pancreatic and duodenal homeobox 1 protein