Adiponectin Is Functionally Active in Human Islets but Does Not Affect Insulin Secretory Function or β-Cell Lipoapoptosis

Context: The adipokine adiponectin has insulin-sensitizing, antiatherogenic, and antiinflammatory properties. Mouse and human adiponectin receptor-1 and -2 have been cloned, both of which are expressed in various tissues and mediate effects of globular and fulllengthadiponectin.Whetheradiponectinaffectsinsulinsecretionand -cell apoptosis and whether plasma adiponectin is associated with -cell function in humans is under investigation. Design and Methods: In human islets from multiorgan donors, we investigated expression of adiponectin receptor-1 and -2. Furthermore,glucose-stimulatedinsulinsecretionwasdeterminedbyRIA.In addition, we investigated fatty acid-induced -cell apoptosis by terminal dUTP nick end labeling and flow-cytometric cell cycle analysis (sub-G1 formation). In humans in vivo, insulin secretory function was measuredduringhyperglycemicclampsin65normalglucose-tolerant subjects.Wedeterminedfirstandsecondphaseofglucose-stimulated, glucagon-like peptide-1-stimulated, and arginine-stimulated insulin secretion. Results: Adiponectin receptor-1 and -2 are expressed in human islets at the mRNA and protein level. Moreover, full-length adiponectin induces phosphorylation of acetyl coenzyme A carboxylase. However, adiponectin did not affect basal or glucose-stimulated insulin secretion or basal or fatty acid-induced -cell apoptosis. In vivo, fasting plasma adiponectin concentrations were not associated with glucosestimulatedfirst-andsecond-phaseinsulinsecretionorwithglucagonlike peptide-1- or arginine-stimulated insulin secretion (all P 0.42). Conclusions: These data support a regulatory role of adiponectin in human islets; however, adiponectin does not seem to affect insulin secretion or basal/fatty acid-induced -cell apoptosis in humans. (J Clin Endocrinol Metab 90: 6707–6713, 2005)