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PMID: 18309108 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Review

Role of mitochondrial dysfunction in insulin resistance.

Circulation research ·Vol. 102 ·No. 4 ·2008-02-29 ·Pages 401-14

Kim JA, Wei Y, Sowers JR

Abstract

Insulin resistance is characteristic of obesity, type 2 diabetes, and components of the cardiometabolic syndrome, including hypertension and dyslipidemia, that collectively contribute to a substantial risk for cardiovascular disease. Metabolic actions of insulin in classic insulin target tissues (eg, skeletal muscle, fat, and liver), as well as actions in nonclassic targets (eg, cardiovascular tissue), help to explain why insulin resistance and metabolic dysregulation are central in the pathogenesis of the cardiometabolic syndrome and cardiovascular disease. Glucose and lipid metabolism are largely dependent on mitochondria to generate energy in cells. Thereby, when nutrient oxidation is inefficient, the ratio of ATP production/oxygen consumption is low, leading to an increased production of superoxide anions. Reactive oxygen species formation may have maladaptive consequences that increase the rate of mutagenesis and stimulate proinflammatory processes. In addition to reactive oxygen species formation, genetic factors, aging, and reduced mitochondrial biogenesis all contribute to mitochondrial dysfunction. These factors also contribute to insulin resistance in classic and nonclassic insulin target tissues. Insulin resistance emanating from mitochondrial dysfunction may contribute to metabolic and cardiovascular abnormalities and subsequent increases in cardiovascular disease. Furthermore, interventions that improve mitochondrial function also improve insulin resistance. Collectively, these observations suggest that mitochondrial dysfunction may be a central cause of insulin resistance and associated complications. In this review, we discuss mechanisms of mitochondrial dysfunction related to the pathophysiology of insulin resistance in classic insulin-responsive tissue, as well as cardiovascular tissue.

MeSH Terms
Animals Cardiovascular Diseases/complications,metabolism Humans Insulin Resistance/physiology Mitochondrial Diseases/complications,metabolism Reactive Oxygen Species/metabolism
Chemicals
Reactive Oxygen Species
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Kim Jeong-A
Department of Internal Medicine, University of Missouri-Columbia School of Medicine, Columbia, Missouri, USA.
Wei Yongzhong
Sowers James R
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Article Info
Journal
Circulation research
Abbr.
Circ Res
ISSN
1524-4571
DOI
10.1161/CIRCRESAHA.107.165472
Published
2008-02-29
Pages
401-14
Language
English
Region
United States
NLM ID
0047103
PMCID
PMC2963150
Subset
IM
Grants
NHLBI NIH HHS · R01 HL073101 · United States
NHLBI NIH HHS · R01 HL073101-01A1 · United States
NHLBI NIH HHS · R01 HL73101-01A1 · United States
External Links
PubMed source DOI: 10.1161/CIRCRESAHA.107.165472 PMC Full Text View journal details
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