Insulin Action in Hyperthyroidism: A Focus on Muscle and Adipose Tissue

Abstract

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.

Zmiany w składzie tkankowym obserwowane w trakcie terapii ciężkich zaburzeń funkcji tarczycy

“…Thyroid hormones regulate the metabolism of the whole human body -triiodothyronine (T3) is necessary to maintain the energy requirements of various cells and tissues, to balance their anabolism and catabolism, and regulate body weight [1][2][3][4]. An abnormal amount of T3 disturbs a number of metabolic processes [2]: shortage of T3 in hypothyroidism reduces basic metabolic rate and thermogenesis, inhibits catabolism and gains total body weight [5]; excess of T3 in hyperthyroidism reverses these processes [6].…”

“…An abnormal amount of T3 disturbs a number of metabolic processes [2]: shortage of T3 in hypothyroidism reduces basic metabolic rate and thermogenesis, inhibits catabolism and gains total body weight [5]; excess of T3 in hyperthyroidism reverses these processes [6]. Specific therapy of hypo- [7,8] and hyperthyroidism [9][10][11] restores proper body mass.…”

The influence of body mass index and low-grade systemic inflammation on thyroid hormone abnormalities in patients with type 2 diabetes

“…It is known that TH levels affect not only glycaemic control but also hepatic and muscular insulin resistance and play a major role in energy homeostasis [1]. Both hypothyroidism and thyrotoxicosis have been shown to increase insulin resistance [2]. Decompensated hyperthyroidism can worsen glycaemic control and predispose patients to diabetic ketoacidosis [3].…”

The Fasting Serum Insulin and Glucose Levels and the Estimated Insulin Resistance in Clinical and Subclinical Hyperthyroid Patients from Saudi Arabia

“…In the present study we observed a several fold increase in the fasting serum insulin levels in the overt and subclinical-hyperthyroid patients. This controversy in the circulating insulin concentration may be attributed to the varying rates of insulin catabolism in these patients [19]. It has been reported that exposure of immature pancreatic islets of the rat to thyroid hormones enhanced their maturation and secretion of the glucose-responsive insulin [20], and induced the expression of thyroid hormone-receptors and deiodinase enzymes [21].…”