Insulin action in morbid obesity: a focus on muscle and adipose tissue.
The aim of this review is to summarize the mechanisms underlying insulin resistance in morbid obesity. Glucose regulation by insulin depends on the suppression of endogenous glucose production and stimulation of glucose disposal. In morbid obesity, glucose production by the liver is increased. Moreover, the sensitivity of glucose metabolism to insulin is impaired both in muscle (due to defects in insulin-stimulated glucose utilization and decreased blood flow) and in adipose tissue (due to decreased blood flow). However, recent studies suggest that expanded total fat mass becomes a major consumer of glucose providing a sink for glucose and compensating for insulin resistance. Metabolism and immunity are closely linked. Bearing in mind the crosstalk between inflammatory pathways and the insulin signaling cascade, adipose tissue derived cytokines may represent a link between inflammation and metabolic signals and mediate, at least in part, insulin resistance. Adipose tissue plays a crucial role by buffering daily influx of dietary fat, suppressing the release of non-esterified fatty acids into the circulation and increasing triacylglycerol clearance. However, in morbid obesity there is an impairment of the normal ability of adipose tissue to buffer fatty acids, despite hyperinsulinemia. Lipotoxicity gradually impairs insulin action in the liver and muscle, aggravating insulin resistance.
Hellenic National Center for Research, Prevention and Treatment of Diabetes Mellitus and its Complications, Athens, Greece.
Panayota
P
Mitrou
Sotirios A
SA
Raptis
George
G
Dimitriadis
D054392:Adipokines / Q000097:blood / Q000378:metabolism; D000273:Adipose Tissue / Q000098:blood supply / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D005943:Gluconeogenesis; D005947:Glucose / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000098:blood supply / Q000276:immunology / Q000378:metabolism; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000098:blood supply / Q000276:immunology / Q000378:metabolism*; D009767:Obesity, Morbid / Q000097:blood / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D011236:Prediabetic State / Q000209:etiology
D054392:Adipokines; D001786:Blood Glucose; D016207:Cytokines; D007328:Insulin; D005947:Glucose