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

Department of Internal Medicine (K.S., N.S., H.S., F.M., M.K., A.F., H.-U.H.), Division of Endocrinology, Metabolism and Pathobiochemistry, University of Tübingen, 72076 Tübingen, Germany; Third Medical Department (M.D.B., D.B., R.G.B.), Justus-Liebig-University of Giessen, 35390 Giessen, Germany; Marienhospital Stuttgart (M.K.), Department of Internal Medicine I, 70199 Stuttgart, Germany; and Third Medical Department (M.S.), University of Leipzig, 04109 Leipzig, Germany

Address all correspondence and requests for reprints to: Hans-Ulrich Häring, M.D., Department of Internal Medicine, University of Tübingen, Otfried-Müller Strasse 10, 72076 Tübingen, Germany. E-mail: hans-ulrich.haering{at}med.uni-tuebingen.de.

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 full-length adiponectin. Whether adiponectin affects insulin secretion and ß-cell apoptosis and whether plasma adiponectin is associated with ß-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-stimulated insulin secretion was determined by RIA. In addition, we investigated fatty acid-induced ß-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 measured during hyperglycemic clamps in 65 normal glucose-tolerant subjects. We determined first and second phase of glucose-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 ß-cell apoptosis. In vivo, fasting plasma adiponectin concentrations were not associated with glucose-stimulated first- and second-phase insulin secretion or with glucagon-like 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 ß-cell apoptosis in humans.

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