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Title: UCP2 mRNA expression is dependent on glucose metabolism in pancreatic islets

Abstract

Highlights: Black-Right-Pointing-Pointer UCP2 mRNA levels are decreased in islets of Langerhans from glucokinase deficient mice. Black-Right-Pointing-Pointer UCP2 mRNA up-regulation by glucose is dependent on glucokinase. Black-Right-Pointing-Pointer Absence of UCP2 increases GSIS of glucokinase heterozygous pancreatic islets. Black-Right-Pointing-Pointer This may protect glucokinase deficient mice from hyperglycemic damages. -- Abstract: Uncoupling Protein 2 (UCP2) is expressed in the pancreatic {beta}-cell, where it partially uncouples the mitochondrial proton gradient, decreasing both ATP-production and glucose-stimulated insulin secretion (GSIS). Increased glucose levels up-regulate UCP2 mRNA and protein levels, but the mechanism for UCP2 up-regulation in response to increased glucose is unknown. The aim was to examine the effects of glucokinase (GK) deficiency on UCP2 mRNA levels and to characterize the interaction between UCP2 and GK with regard to glucose-stimulated insulin secretion in pancreatic islets. UCP2 mRNA expression was reduced in GK+/- islets and GK heterozygosity prevented glucose-induced up-regulation of islet UCP2 mRNA. In contrast to UCP2 protein function UCP2 mRNA regulation was not dependent on superoxide generation, but rather on products of glucose metabolism, because MnTBAP, a superoxide dismutase mimetic, did not prevent the glucose-induced up-regulation of UCP2. Glucose-stimulated insulin secretion was increased in UCP2-/- and GK+/- islets compared with GK+/- islets and UCP2 deficiencymore » improved glucose tolerance of GK+/- mice. Accordingly, UCP2 deficiency increased ATP-levels of GK+/- mice. Thus, the compensatory down-regulation of UCP2 is involved in preserving the insulin secretory capacity of GK mutant mice and might also be implicated in limiting disease progression in MODY2 patients.« less

Authors:
 [1];  [2]
  1. Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (United States)
  2. (Denmark)
Publication Date:
OSTI Identifier:
22207636
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 417; Journal Issue: 1; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ATP; CARBOXYLIC ACIDS; GLUCOSE; HEXOKINASE; INSULIN; MESSENGER-RNA; METABOLISM; MICE; MITOCHONDRIA; PANCREAS; POLYMERASE CHAIN REACTION; SECRETION; SUPEROXIDE DISMUTASE

Citation Formats

Dalgaard, Louise T., E-mail: ltd@ruc.dk, and Department of Science, Systems and Models, Roskilde University. UCP2 mRNA expression is dependent on glucose metabolism in pancreatic islets. United States: N. p., 2012. Web. doi:10.1016/J.BBRC.2011.11.148.
Dalgaard, Louise T., E-mail: ltd@ruc.dk, & Department of Science, Systems and Models, Roskilde University. UCP2 mRNA expression is dependent on glucose metabolism in pancreatic islets. United States. doi:10.1016/J.BBRC.2011.11.148.
Dalgaard, Louise T., E-mail: ltd@ruc.dk, and Department of Science, Systems and Models, Roskilde University. Fri . "UCP2 mRNA expression is dependent on glucose metabolism in pancreatic islets". United States. doi:10.1016/J.BBRC.2011.11.148.
@article{osti_22207636,
title = {UCP2 mRNA expression is dependent on glucose metabolism in pancreatic islets},
author = {Dalgaard, Louise T., E-mail: ltd@ruc.dk and Department of Science, Systems and Models, Roskilde University},
abstractNote = {Highlights: Black-Right-Pointing-Pointer UCP2 mRNA levels are decreased in islets of Langerhans from glucokinase deficient mice. Black-Right-Pointing-Pointer UCP2 mRNA up-regulation by glucose is dependent on glucokinase. Black-Right-Pointing-Pointer Absence of UCP2 increases GSIS of glucokinase heterozygous pancreatic islets. Black-Right-Pointing-Pointer This may protect glucokinase deficient mice from hyperglycemic damages. -- Abstract: Uncoupling Protein 2 (UCP2) is expressed in the pancreatic {beta}-cell, where it partially uncouples the mitochondrial proton gradient, decreasing both ATP-production and glucose-stimulated insulin secretion (GSIS). Increased glucose levels up-regulate UCP2 mRNA and protein levels, but the mechanism for UCP2 up-regulation in response to increased glucose is unknown. The aim was to examine the effects of glucokinase (GK) deficiency on UCP2 mRNA levels and to characterize the interaction between UCP2 and GK with regard to glucose-stimulated insulin secretion in pancreatic islets. UCP2 mRNA expression was reduced in GK+/- islets and GK heterozygosity prevented glucose-induced up-regulation of islet UCP2 mRNA. In contrast to UCP2 protein function UCP2 mRNA regulation was not dependent on superoxide generation, but rather on products of glucose metabolism, because MnTBAP, a superoxide dismutase mimetic, did not prevent the glucose-induced up-regulation of UCP2. Glucose-stimulated insulin secretion was increased in UCP2-/- and GK+/- islets compared with GK+/- islets and UCP2 deficiency improved glucose tolerance of GK+/- mice. Accordingly, UCP2 deficiency increased ATP-levels of GK+/- mice. Thus, the compensatory down-regulation of UCP2 is involved in preserving the insulin secretory capacity of GK mutant mice and might also be implicated in limiting disease progression in MODY2 patients.},
doi = {10.1016/J.BBRC.2011.11.148},
journal = {Biochemical and Biophysical Research Communications},
number = 1,
volume = 417,
place = {United States},
year = {Fri Jan 06 00:00:00 EST 2012},
month = {Fri Jan 06 00:00:00 EST 2012}
}