Modulation of Circulating and Adipose Tissue Adiponectin Levels by Antidiabetic Therapy

Abstract

The relationship between insulin action and control of the adipocyte-derived factor adiponectin was studied in age-and weight-matched obese individuals with type 2 diabetes failing sulfonylurea therapy. After initial metabolic characterization, subjects were randomized to troglitazone or metformin treatment groups; all subjects received glyburide (10 mg BID) as well. Treatment was continued for 3 months. The extent of glycemic control after treatment was similar in both groups. However, the increase in maximal insulin-stimulated glucose disposal rate was greater following troglitazone therapy (؉44%) compared with metformin treatment (؉20%). Troglitazone treatment increased serum adiponectin levels nearly threefold. There was no change in serum adiponectin with metformin treatment. A positive correlation was found between increases in wholebody glucose disposal rates and serum adiponectin levels after troglitazone; no such relationship was seen with metformin. The adiponectin protein content of subcutaneous abdominal adipocytes was increased following troglitazone treatment and unchanged after metformin. Adiponectin release from adipocytes was also augmented with troglitazone treatment. Adiponectin was present in adipocytes and plasma in several multimeric forms; a trimer was the major form secreted from adipocytes. These results indicate that increases in adiponectin content and secretion are associated with improved insulin action but are not directly related to glycemic control. Modulation of adipocyte function, including upregulation of adiponectin synthesis and secretion, may be an important mechanism by which thiazolidinediones influence insulin action. Diabetes

Impact of metformin versus repaglinide on non-glycaemic cardiovascular risk markers related to inflammation and endothelial dysfunction in non-obese patients with type 2 diabetes

“…For albuminuria, also an increase has been observed after metformin therapy (37). The observed lack of significant difference in the present study in the levels of IL-6, fibrinogen and adiponectin is in accordance with previous data for metformin in predominantly obese patients with T2DM (20,24,26,37,48,51). Repaglinide has been shown to decrease levels of CRP, IL-6 and PAI-1-ag (21)(22)(23)27) and either to decrease (27) or have no significant effect on levels of fibrinogen (21,52) in predominantly obese patients with T2DM.…”

“…Thus, biological mechanisms both dependent and independent of glycaemia might influence the CVD biomarkers. As yet, few studies have compared the effect of various anti-hyperglycaemic treatment regimens on CVD biomarkers, and most studies were in obese patients with T2DM (17,(19)(20)(21)(22)(23)(24)(25)(26)(27).…”

Circulating adiponectin levels, body composition and obesity-related variables in Prader–Willi syndrome: comparison with obese subjects

“…[9][10][11][12] Adiponectin is abundant in the circulation of nondiabetic humans, but is decreased in patients with obesity, type 2 diabetes and cardiovascular disease and higher in women than in men. 13 In addition, treatment of obese type 2 diabetics with the peroxisome proliferator-activated receptor, gamma (PPARG) agonist troglitazone was associated with a three-fold increase in circulating adiponectin levels. 13 Thus, adiponectin may play an important role in the links between obesity, insulin resistance, type 2 diabetes and risk of cardiovascular disease.…”

“…13 In addition, treatment of obese type 2 diabetics with the peroxisome proliferator-activated receptor, gamma (PPARG) agonist troglitazone was associated with a three-fold increase in circulating adiponectin levels. 13 Thus, adiponectin may play an important role in the links between obesity, insulin resistance, type 2 diabetes and risk of cardiovascular disease.…”

The effects of exercise and adipose tissue lipolysis on plasma adiponectin concentration and adiponectin receptor expression in human skeletal muscle

“…Membranes probed with a primary monoclonal antibody (MAB 10 651) raised against an epitope in the globular domain (gAcrp30, amino acids 104 244) of full-length adiponectin protein showed three bands at , 28 kDa, , 55 kDa and , 85 kDa according to the molecular weight marker. These three bands likely correspond with the adiponectin monomeric (1,5,33,34), dimeric (2, 5, 34) and trimeric (1,6,34) forms. The band observed between 28 and 34 kDa likely represents one (or more) of the glycolysated isoforms (35).…”