Insulin action in hyperthyroidism: a focus on muscle and adipose tissue.
Hyperthyroidism leads to an enhanced demand for glucose, which is primarily provided by increased rates of hepatic glucose production due to increased gluconeogenesis (in the fasting state) and increased Cori cycle activity (in the late postprandial and fasting state). Adipose tissue lipolysis is increased in the fasting state, resulting in increased production of glycerol and nonesterified fatty acids. Under these conditions, increased glycerol generated by lipolysis and increased amino acids generated by proteolysis are used as substrates for gluconeogenesis. Increased nonesterified fatty acid levels are necessary to stimulate gluconeogenesis and provide substrate for oxidation in other tissues (such as muscle). In the postprandial period, insulin-stimulated glucose uptake by the skeletal muscle has been found to be normal or increased, mainly due to increased blood flow. Under hyperthyroid conditions, insulin-stimulated rates of glycogen synthesis in skeletal muscle are decreased, whereas there is a preferential increase in the rates of lactate formation vs. glucose oxidation leading to increased Cori cycle activity. In hyperthyroidism, the Cori cycle could be considered as a large substrate cycle; by maintaining a high flux through it, a dynamic buffer of glucose and lactate is provided, which can be used by other tissues as required. Moreover, lipolysis is rapidly suppressed to normal after the meal to facilitate the disposal of glucose by the insulin-resistant muscle. This ensures the preferential use of glucose when available and helps to preserve fat stores.
Hellenic National Center for Research, Prevention, and Treatment of Diabetes Mellitus and Its Complications, 10675 Athens, Greece.
Panayota
P
Mitrou
Sotirios A
SA
Raptis
George
G
Dimitriadis
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D006980:Hyperthyroidism / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D050356:Lipid Metabolism / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism*
D007328:Insulin; D005947:Glucose