title: Molecular mechanisms of diabetes and atherosclerosis: role of adiponectin.
abstract: Type 2 diabetes mellitus (T2DM) is a disease characterized by inadequate beta-cell response due to progressive insulin resistance that typically accompanies physical inactivity and weight gain. T2DM is associated with substantial morbidity and mortality related to the associated atherosclerotic cardiovascular risks and diabetic vasculopathies, including microangiopathies (e.g., blindness and renal failure) and macroangiopathies (atherosclerosis). The increasing global prevalence of T2DM is linked to the rising rates of obesity, especially abdominal obesity. Visceral fat accumulation is upstream of obesity-related disorders including atherosclerotic cardiovascular disease (ACVD), and is associated with impaired insulin sensitivity and atherosclerosis through dysregulated production of adipocytokines, especially hypoadiponectinemia. This review article discusses the pathophysiological mechanisms responsible for T2DM and atherosclerosis, focusing on adiponectin. Clinical and experimental studies have shown that hypoadiponectinemia contributes to a variety of life style-related diseases including T2DM and atherosclerosis. It is likely that life-style modification, visceral fat reduction and use of medications that increase serum adiponectin levels (e.g., rimonabant, thiazolidinediones, fibrates, angiotensin receptor blocker and mineralocorticoid receptor blockade) when provided in combination can improve hypoadiponectinemia and thus prevent the development of life style-related diseases including T2DM and ACVD.
authors.affiliation: Department of Metabolism and Atherosclerosis, Graduate School of Medicine, Osaka University, 2-2 B-5, Yamada-oka, Suita, Osaka 565-0871, Japan. kkishida@imed2.med.osaka-u.ac.jp
authors.forename: Ken
authors.initials: K
authors.lastname: Kishida
authors.forename: Tohru
authors.initials: T
authors.lastname: Funahashi
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
mesh_terms: D052242:Adiponectin / Q000096:biosynthesis / Q000097:blood* / Q000378:metabolism*; D000818:Animals; D019440:Anti-Obesity Agents / Q000627:therapeutic use; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D003925:Diabetic Angiopathies / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D056128:Obesity, Abdominal / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D051381:Rats; D040242:Risk Reduction Behavior; D012891:Sleep Apnea Syndromes / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology
chemical_list: D052242:Adiponectin; D019440:Anti-Obesity Agents