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Calbindin-D9k Ablation Disrupt Glucose/Pancreatic Insulin Homeostasis

It has been proposed that cellular Ca(2+) signals activate hormone secretion. In pancreatic β cells, which produce insulin, Ca(2+) 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 pl...

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Autores principales: Ahn, Changhwan, Lee, Dongoh, Lee, Jae-Hwan, Yang, Hyun, An, Beum-Soo, Jeung, Eui-Bae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063278/
https://www.ncbi.nlm.nih.gov/pubmed/27736926
http://dx.doi.org/10.1371/journal.pone.0164527
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author Ahn, Changhwan
Lee, Dongoh
Lee, Jae-Hwan
Yang, Hyun
An, Beum-Soo
Jeung, Eui-Bae
author_facet Ahn, Changhwan
Lee, Dongoh
Lee, Jae-Hwan
Yang, Hyun
An, Beum-Soo
Jeung, Eui-Bae
author_sort Ahn, Changhwan
collection PubMed
description It has been proposed that cellular Ca(2+) signals activate hormone secretion. In pancreatic β cells, which produce insulin, Ca(2+) 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 (K(ir)6.2), 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.
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spelling pubmed-50632782016-11-04 Calbindin-D9k Ablation Disrupt Glucose/Pancreatic Insulin Homeostasis Ahn, Changhwan Lee, Dongoh Lee, Jae-Hwan Yang, Hyun An, Beum-Soo Jeung, Eui-Bae PLoS One Research Article It has been proposed that cellular Ca(2+) signals activate hormone secretion. In pancreatic β cells, which produce insulin, Ca(2+) 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 (K(ir)6.2), 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. Public Library of Science 2016-10-13 /pmc/articles/PMC5063278/ /pubmed/27736926 http://dx.doi.org/10.1371/journal.pone.0164527 Text en © 2016 Ahn et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Ahn, Changhwan
Lee, Dongoh
Lee, Jae-Hwan
Yang, Hyun
An, Beum-Soo
Jeung, Eui-Bae
Calbindin-D9k Ablation Disrupt Glucose/Pancreatic Insulin Homeostasis
title Calbindin-D9k Ablation Disrupt Glucose/Pancreatic Insulin Homeostasis
title_full Calbindin-D9k Ablation Disrupt Glucose/Pancreatic Insulin Homeostasis
title_fullStr Calbindin-D9k Ablation Disrupt Glucose/Pancreatic Insulin Homeostasis
title_full_unstemmed Calbindin-D9k Ablation Disrupt Glucose/Pancreatic Insulin Homeostasis
title_short Calbindin-D9k Ablation Disrupt Glucose/Pancreatic Insulin Homeostasis
title_sort calbindin-d9k ablation disrupt glucose/pancreatic insulin homeostasis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063278/
https://www.ncbi.nlm.nih.gov/pubmed/27736926
http://dx.doi.org/10.1371/journal.pone.0164527
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