Uncoupling Proteins: Role in Insulin Resistance and Insulin Insufficiency

Authors: B.Chan, Catherine; Harper, Mary-Ellen

Source: Current Diabetes Reviews, Volume 2, Number 3, August 2006 , pp. 271-283(13)

Publisher: Bentham Science Publishers

Buy & download fulltext article:

Price: $62.88 plus tax (Refund Policy)

Abstract:

Uncoupling proteins (UCPs) are modulators of mitochondrial metabolism that have been implicated in the development of both insulin resistance and insulin insufficiency, the two major pathophysiological events associated with type 2 diabetes. UCP2 mRNA is expressed in a wide range of tissues; however UCP2 protein expression is restricted to fewer tissues, including the endocrine pancreas, spleen, stomach, brain and the lung. To date, its role in the pathophysiology of diabetes has been most strongly associated with impaired glucosestimulated insulin secretion from the β-cell, particularly after its induction by free fatty acids. The physiological role of UCP2 remains controversial, but it may act as a downstream signal transducer of superoxide. UCP3 mRNA and protein are expressed in relatively few tissues, predominately skeletal muscle, brown adipose tissue and heart. Increased expression of UCP3 in skeletal muscle is associated with protection from diet-induced insulin resistance in mice. In patients with type 2 diabetes UCP3 protein in muscle is reduced by 50%compared to healthy controls. The primary physiological role of the novel UCPs does not appear to be protection against positive energy balance and obesity; this is based largely on findings from studies of UCP2 and UCP3 knockout mice and from observed increases in UCP3 expression with fasting. The mechanism(s) of action of UCP2 and UCP3 are poorly understood. However, findings support roles for UCP2 and UCP3 as modifiers of fatty acid metabolism and in mitigating damage from reactive oxygen species.

Keywords: Uncoupling proteins; Insulin secretion; Insulin resistance; Reactive oxygen species; Fatty acid metabolism

Document Type: Research article

DOI: http://dx.doi.org/10.2174/157339906777950660

Affiliations: 1: Department of Biomedical Sciences, University of PEI, 550 University Ave., Charlottetown, PE C1A 4P3 Canada.

Publication date: 2006-08-01

More about this publication?

Current Diabetes Reviews publishes frontier reviews on all the latest advances on diabetes and its related areas e.g. pharmacology, pathogenesis, complications, epidemiology, clinical care, and therapy.

The journal's aim is to publish the highest quality review articles dedicated to clinical research in the field. The journal is essential reading for all researchers and clinicians who are involved in the field of diabetes.

Uncoupling Proteins: Role in Insulin Resistance and Insulin Insufficiency

Buy & download fulltext article:

Tools

Key

Text size:

Useful pages