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Chronic glucolipotoxic conditions in pancreatic islets impair insulin secretion due to dysregulated calcium dynamics, glucose responsiveness and mitochondrial activity

BACKGROUND: In the progression towards diabetes, glucolipotoxicity is one of the main causes of pancreatic beta cell pathology. The aim of this study was to examine the in vitro effects of chronic glucolipotoxic conditions on cellular responses in pancreatic islets, including glucose and fat metabol...

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Autores principales: Somesh, Baggavalli P, Verma, Mahesh Kumar, Sadasivuni, Manoj Kumar, Mammen-Oommen, Anup, Biswas, Sanghamitra, Shilpa, Pavagada C, Reddy, Ashok Kumar, Yateesh, Aggunda N, Pallavi, Puttrevana M, Nethra, Siddaraju, Smitha, Rachapalli, Neelima, Korrapati, Narayanan, Usha, Jagannath, Madanahalli R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3704974/
https://www.ncbi.nlm.nih.gov/pubmed/23815372
http://dx.doi.org/10.1186/1471-2121-14-31
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author Somesh, Baggavalli P
Verma, Mahesh Kumar
Sadasivuni, Manoj Kumar
Mammen-Oommen, Anup
Biswas, Sanghamitra
Shilpa, Pavagada C
Reddy, Ashok Kumar
Yateesh, Aggunda N
Pallavi, Puttrevana M
Nethra, Siddaraju
Smitha, Rachapalli
Neelima, Korrapati
Narayanan, Usha
Jagannath, Madanahalli R
author_facet Somesh, Baggavalli P
Verma, Mahesh Kumar
Sadasivuni, Manoj Kumar
Mammen-Oommen, Anup
Biswas, Sanghamitra
Shilpa, Pavagada C
Reddy, Ashok Kumar
Yateesh, Aggunda N
Pallavi, Puttrevana M
Nethra, Siddaraju
Smitha, Rachapalli
Neelima, Korrapati
Narayanan, Usha
Jagannath, Madanahalli R
author_sort Somesh, Baggavalli P
collection PubMed
description BACKGROUND: In the progression towards diabetes, glucolipotoxicity is one of the main causes of pancreatic beta cell pathology. The aim of this study was to examine the in vitro effects of chronic glucolipotoxic conditions on cellular responses in pancreatic islets, including glucose and fat metabolism, Calcium mobilization, insulin secretion and insulin content. RESULTS: Exposure of islets to chronic glucolipotoxic conditions decreased glucose stimulated insulin secretion in vitro. Reduced protein levels of Glut2/slc2a2, and decreased glucokinase and pyruvate carboxylase mRNA levels indicated a significant lowering in glucose sensing. Concomitantly, both fatty acid uptake and triglyceride accumulation increased significantly while fatty acid oxidation decreased. This general suppression in glucose metabolism correlated well with a decrease in mitochondrial number and activity, reduction in cellular ATP content and dampening of the TCA cycle. Further, we also observed a decrease in IP3 levels and lower Calcium mobilization in response to glucose. Importantly, chronic glucolipotoxic conditions in vitro decreased insulin gene expression, insulin content, insulin granule docking (to the plasma membrane) and insulin secretion. CONCLUSIONS: Our results present an integrated view of the effects of chronic glucolipotoxic conditions on known and novel signaling events, in vitro, that results in reduced glucose responsiveness and insulin secretion.
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spelling pubmed-37049742013-07-10 Chronic glucolipotoxic conditions in pancreatic islets impair insulin secretion due to dysregulated calcium dynamics, glucose responsiveness and mitochondrial activity Somesh, Baggavalli P Verma, Mahesh Kumar Sadasivuni, Manoj Kumar Mammen-Oommen, Anup Biswas, Sanghamitra Shilpa, Pavagada C Reddy, Ashok Kumar Yateesh, Aggunda N Pallavi, Puttrevana M Nethra, Siddaraju Smitha, Rachapalli Neelima, Korrapati Narayanan, Usha Jagannath, Madanahalli R BMC Cell Biol Research Article BACKGROUND: In the progression towards diabetes, glucolipotoxicity is one of the main causes of pancreatic beta cell pathology. The aim of this study was to examine the in vitro effects of chronic glucolipotoxic conditions on cellular responses in pancreatic islets, including glucose and fat metabolism, Calcium mobilization, insulin secretion and insulin content. RESULTS: Exposure of islets to chronic glucolipotoxic conditions decreased glucose stimulated insulin secretion in vitro. Reduced protein levels of Glut2/slc2a2, and decreased glucokinase and pyruvate carboxylase mRNA levels indicated a significant lowering in glucose sensing. Concomitantly, both fatty acid uptake and triglyceride accumulation increased significantly while fatty acid oxidation decreased. This general suppression in glucose metabolism correlated well with a decrease in mitochondrial number and activity, reduction in cellular ATP content and dampening of the TCA cycle. Further, we also observed a decrease in IP3 levels and lower Calcium mobilization in response to glucose. Importantly, chronic glucolipotoxic conditions in vitro decreased insulin gene expression, insulin content, insulin granule docking (to the plasma membrane) and insulin secretion. CONCLUSIONS: Our results present an integrated view of the effects of chronic glucolipotoxic conditions on known and novel signaling events, in vitro, that results in reduced glucose responsiveness and insulin secretion. BioMed Central 2013-07-01 /pmc/articles/PMC3704974/ /pubmed/23815372 http://dx.doi.org/10.1186/1471-2121-14-31 Text en Copyright © 2013 Somesh et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Somesh, Baggavalli P
Verma, Mahesh Kumar
Sadasivuni, Manoj Kumar
Mammen-Oommen, Anup
Biswas, Sanghamitra
Shilpa, Pavagada C
Reddy, Ashok Kumar
Yateesh, Aggunda N
Pallavi, Puttrevana M
Nethra, Siddaraju
Smitha, Rachapalli
Neelima, Korrapati
Narayanan, Usha
Jagannath, Madanahalli R
Chronic glucolipotoxic conditions in pancreatic islets impair insulin secretion due to dysregulated calcium dynamics, glucose responsiveness and mitochondrial activity
title Chronic glucolipotoxic conditions in pancreatic islets impair insulin secretion due to dysregulated calcium dynamics, glucose responsiveness and mitochondrial activity
title_full Chronic glucolipotoxic conditions in pancreatic islets impair insulin secretion due to dysregulated calcium dynamics, glucose responsiveness and mitochondrial activity
title_fullStr Chronic glucolipotoxic conditions in pancreatic islets impair insulin secretion due to dysregulated calcium dynamics, glucose responsiveness and mitochondrial activity
title_full_unstemmed Chronic glucolipotoxic conditions in pancreatic islets impair insulin secretion due to dysregulated calcium dynamics, glucose responsiveness and mitochondrial activity
title_short Chronic glucolipotoxic conditions in pancreatic islets impair insulin secretion due to dysregulated calcium dynamics, glucose responsiveness and mitochondrial activity
title_sort chronic glucolipotoxic conditions in pancreatic islets impair insulin secretion due to dysregulated calcium dynamics, glucose responsiveness and mitochondrial activity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3704974/
https://www.ncbi.nlm.nih.gov/pubmed/23815372
http://dx.doi.org/10.1186/1471-2121-14-31
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