Insulin-sensitizing properties of adiponectin.
Adiponectin administration improves glucose tolerance in rodents. This is due to both reductions in hepatic glucose production, and likely improved insulin stimulated glucose disposal in skeletal muscle. Adiponectin's effects in both liver and muscle are believed to be due in large part to AMP-activated protein kinase (AMPK) activation, resulting in a reduction in hepatic gluconeogenic enzymes and increased fatty acid oxidation and reduced ectopic lipid deposition in muscle. In addition, adiponectin can robustly stimulate mitochondrial biogenesis, at least in muscle, and this appears to be due to AMPK-independent mechanisms. Various treatments successful at improving insulin response (thiazolidinediones (TZDs), n-3 polyunsaturated fatty acid (PUFA) supplementation) also stimulate adiponectin production. Obesity and insulin resistance are often characterized by both a state of resistance to adiponectin (both liver and muscle), as well as a reduction in total circulating adiponectin concentrations. The mechanisms underlying the impaired response of muscle and liver to adiponectin have not been clearly elucidated. Surprisingly, the significance of adiponectin resistance, at least in muscle, is not entirely clear. While the development of adiponectin resistance precedes intramuscular lipid accumulation and impaired insulin response in high-fat fed rodents, the restoration of adiponectin response does not appear to be necessary in order to restore insulin response in muscle. Further research examining the cellular mechanisms underlying the development of adiponectin resistance, and the importance of treating this, needs to be conducted.
Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada N1G2W1.
Justine M
JM
Tishinsky
Lindsay E
LE
Robinson
David J
DJ
Dyck
D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D009132:Muscles / Q000378:metabolism
D052242:Adiponectin; D007328:Insulin