Resistin and obesity-associated insulin resistance.
Obesity is a major risk factor for insulin resistance and type 2 diabetes mellitus. Adipocytes secrete numerous substances that might contribute to peripheral insulin sensitivity. These include leptin, tumor necrosis factor alpha, Acrp30/adiponectin/adipoQ and interleukin 6, the potential roles of which are briefly reviewed here. Thiazolidinedione (TZD) antidiabetic drugs regulate gene transcription by binding to peroxisome proliferator activated receptor gamma, a nuclear hormone receptor found at its highest levels in adipocytes. A search for genes that are downregulated by TZDs in mouse adipocytes led to the discovery of an adipose-specific secreted protein called resistin. Resistin circulates in the mouse, with increased levels in obesity, and has effects on glucose homeostasis that oppose those of insulin. Thus, resistin is a potential link between TZDs, obesity and insulin resistance in the mouse. Future studies must address the mechanism of action and biological role of resistin and related family members in mice and humans.
Steppan
Claire M
CM
Division of Endocrinology, Diabetes, and Metabolism, Depts of Medicine and Genetics and The Penn Diabetes Center, University of Pennsylvania Medical Center, Philadelphia, PA 19104-6149, USA.
Lazar
Mitchell A
MA
D000273:Adipose Tissue / Q000502:physiology; D000818:Animals; D004702:Endocrine Glands / Q000502:physiology; D006729:Hormones, Ectopic / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D020932:Nerve Growth Factor; D009765:Obesity / Q000503:physiopathology*; D011506:Proteins; D052243:Resistin
D006729:Hormones, Ectopic; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D052243:Resistin; C413576:Retnla protein, mouse; D020932:Nerve Growth Factor