Inhibition of UCP2 expression reverses diet-induced diabetes mellitus by effects on both insulin secretion and action

De Souza  CT; Araujo  EP; Stoppiglia  LFPauli  JRRopelle  ERocco  SAMarin  RMFranchini  KGCarvalheira  JBSaad  MJ

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Inhibition of UCP2 expression reverses diet-induced diabetes mellitus by effects on both insulin secretion and action

机译：Inhibition of UCP2 expression reverses diet-induced diabetes mellitus by effects on both insulin secretion and action

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Recent characterization of the ability of uncoupling protein 2 (UCP2) to reduce ATP production and inhibit insulin secretion by pancreatic beta-cells has placed this mitochondrial protein as a candidate target for therapeutics in diabetes mellitus. In the present study we evaluate the effects of short-term treatment of two animal models of type 2 diabetes mellitus with an antisense oligonucleotide to UCP2. In both models, Swiss mice ( made obese and diabetic by a hyperlipidic diet) and ob/ob mice, the treatment resulted in a significant improvement in the hyperglycemic syndrome. This effect was due not only to an improvement of insulin secretion, but also to improved peripheral insulin action. In isolated pancreatic islets, the partial inhibition of UCP2 increased ATP content, followed by increased glucose-stimulated insulin secretion. This was not accompanied by increased expression of enzymes involved in protection against oxidative stress. The evaluation of insulin action in peripheral tissues revealed that the inhibition of UCP2 expression significantly improved insulin signal transduction in adipose tissue. In conclusion, short-term inhibition of UCP2 expression ameliorates the hyperglycemic syndrome in two distinct animal models of obesity and diabetes. Metabolic improvement is due to a combined effect on insulin-producing pancreatic islets and in at least one peripheral tissue that acts as a target for insulin.

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《The FASEB Journal》 |2007年第4期|1153-1163|共11页
作者
De Souza CT; Araujo EP; Stoppiglia LFPauli JRRopelle ERocco SAMarin RMFranchini KGCarvalheira JBSaad MJ;
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作者单位

Univ Estadual Campinas, Dept Internal Med, Campinas, SP, Brazil;

Univ Estadual Campinas, Dept Phys & Biophys, Campinas, SP, Brazil;

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正文语种英语
中图分类生物化学;
关键词
short-term inhibition of UCP2; antisense oligonucleotide; ATP synthase; anti-UCP2 antibody; BETA-CELL DYSFUNCTION; UNCOUPLING PROTEINS UCP2; PANCREATIC-ISLETS; RECEPTOR SUBSTRATE-1; OXIDATIVE STRESS; OBESITY; RESISTANCE; MICE; OVEREXPRESSION; HYPERINSULINEMIA;

Inhibition of UCP2 expression reverses diet-induced diabetes mellitus by effects on both insulin secretion and action

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