title: Thyroid hormone excess and glucose intolerance.
abstract: The elevated plasma glucose levels in hyperthyroidism may be explained by increased rates of endogenous glucose production, due mainly to increased gluconeogenesis. The rates of insulin-stimulated glucose disposal in peripheral tissues in hyperthyroidism have been found, in general, either normal or increased. Skeletal muscle is the most important tissue for the disposal of glucose in response to insulin. In this tissue, insulin increases glucose disposal by stimulating glucose transport, glucose phosphorylation/glycolysis, glycogen synthesis and glucose oxidation. Studies examining insulin-stimulated glucose metabolism in skeletal muscle have suggested that, in the hyperthyroid state, it may be of primary importance to increase the rates of glycolysis and lactate formation relative to glucose oxidation in this tissue in order to provide substrate for gluconeogenesis (increase Cori cycle activity). This effect will be achieved primarily by a decrease in glycogen synthesis and an increase in glycogenolysis. When hyperthyroidism becomes more severe, an increased rate of glucose uptake into muscle may then be necessary since the increased conversion of glycogen to lactate could not be sustained for prolonged periods and might lead to a depletion in glycogen stores. This mechanism would ensure that the level of glucose in plasma is kept normal or slightly increased. Thus, an increased Cori cycle activity may be a necessary mechanism to provide optimal conditions in hyperthyroidism for the control of glucose utilization without increasing the risk of hypoglycemia. In addition to lactate, increased rates of gluconeogenesis in hyperthyroidism can also be sustained by increased plasma concentrations of amino acids (mostly glutamine and alanine) and glycerol, as well as by increased plasma concentrations of free fatty acids.
authors.affiliation: 2nd Department of Internal Medicine, Research Institute and Diabetes Center, Athens University, Evangelismos Hospital, Athens, Greece. dimitriadis@hndc.gr
authors.forename: G D
authors.initials: GD
authors.lastname: Dimitriadis
authors.forename: S A
authors.initials: SA
authors.lastname: Raptis
mesh_terms: D000818:Animals; D005746:Gastric Emptying; D005947:Glucose / Q000378:metabolism; D018149:Glucose Intolerance; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050356:Lipid Metabolism; D013963:Thyroid Hormones / Q000378:metabolism*
chemical_list: D007328:Insulin; D013963:Thyroid Hormones; D005947:Glucose