Adiponectin is a cytokine produced by adipocytes and is termed an “ adipokine.” Adiponectin functions as an insulin
sensitizer. Downregulation of adiponectin receptors and low levels of adiponectin have been associated with obesity-linked
insulin resistance. Exercise and dietary changes have been shown to raise low levels of adiponectin in obese
adolescents. Additionally, sarpogrelate hydrochloride, a 5-HT2A antagonist, elevates low adiponectin levels and
normalizes other factors associated with vascular changes seen in type 2 diabetes.
Enzyminhibitor
This 244-residue anti-diabetic hormone (MWmonomer = 30 kDa; Symbol: Ad) is a adipocyte-derived polypeptide that regulates energy homeostasis and glucose and lipid metabolism, mainly by increasing the insulin responsiveness of susceptible cells and by stimulating the phosphorylation/activation of the 5'-AMP-activated protein kinase, or AMPK. Adiponectin circulates in human plasma mainly as a 180-kDa middle molecular weight (MMW) hexamer and a high molecular weight (HMW) multimer of approximately 360 kDa. It has four topologically distinct regions: a short signal sequence targeting the hormone for secretion; a short species-variant region; a 65-residue region resembling collagens; and a globular domain. This adipokine, which bears similarities in domain structure to the complement protein C1q, is processed into at least three homomeric complexes, trimer, hexamer, and a high-molecularweight (HMW) octadecamer. In skeletal muscle. AMPK is stimulated with globular and full-length Ad, whereas AMPK is only stimulated by fulllength Ad in liver. Ad stimulates phosphorylation of acetyl coenzyme A carboxylase (ACC), fatty-acid oxidation, glucose uptake and lactate production in myocytes, phosphorylation of ACC and reduction of molecules involved in gluconeogenesis in the liver, and reduction of glucose levels in vivo. Inhibition of AMPK activation (See Dominant Negative Mutants) blocks each of these effects, indicating that stimulation of glucose utilization and fatty-acid oxidation by Ad occurs through activation of AMPK.
