The Impact of Adipose Tissue on Insulin Resistance in Acromegaly

Despite decreased body fat and increased muscle mass, insulin resistance, and overt diabetes are present in acromegaly. GH antagonizes insulin action and promotes insulin resistance. Early evidence supports a role for liver and skeletal muscles, but later studies underline AT as one of the contributors to the development of insulin resistance in acromegaly. AT inflammation, lipolysis and release of free fatty acids, ectopic or altered fat deposition and distribution, and impaired adipogenesis are the main mechanisms to explain AT-driven insulin resistance in active acromegaly. Treatment modalities impact differently on glucose metabolism, but not on AT deposition that is predominantly in the trunk and visceral depots. An individualized approach for the management of diabetes based on the mechanisms of AT-driven insulin resistance would be desirable in the future. Adipose tissue (AT) is recognized as key contributor to the systemic insulin resistance and overt diabetes seen in metabolic syndrome. Acromegaly is a disease characterized by excessive secretion of growth hormone (GH) and insulin-like growth factor I (IGF-I). GH is known both for its action on AT and for its detrimental effect on glucose metabolism and insulin signaling. In active acromegaly, while body fat deports are diminished, insulin resistance is increased. Early studies have demonstrated defects in insulin action, both at the hepatic and extrahepatic (i.e., muscle and fat) levels, in active disease. This review discusses recent data suggesting that AT inflammation, altered AT distribution, and impaired adipogenesis are potential mechanisms contributing to systemic insulin resistance in acromegaly. Adipose tissue (AT) is recognized as key contributor to the systemic insulin resistance and overt diabetes seen in metabolic syndrome. Acromegaly is a disease characterized by excessive secretion of growth hormone (GH) and insulin-like growth factor I (IGF-I). GH is known both for its action on AT and for its detrimental effect on glucose metabolism and insulin signaling. In active acromegaly, while body fat deports are diminished, insulin resistance is increased. Early studies have demonstrated defects in insulin action, both at the hepatic and extrahepatic (i.e., muscle and fat) levels, in active disease. This review discusses recent data suggesting that AT inflammation, altered AT distribution, and impaired adipogenesis are potential mechanisms contributing to systemic insulin resistance in acromegaly.