Adiponectin is functionally active in human islets but does not affect insulin secretory function or beta-cell lipoapoptosis

J Clin Endocrinol Metab. 2005 Dec;90(12):6707-13. doi: 10.1210/jc.2005-0467. Epub 2005 Oct 4.

Abstract

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 beta-cell apoptosis and whether plasma adiponectin is associated with beta-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 beta-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 beta-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 beta-cell apoptosis in humans.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / pharmacology
  • Adiponectin / physiology*
  • Apoptosis / physiology*
  • Fatty Acids, Nonesterified / pharmacology*
  • Female
  • Humans
  • In Vitro Techniques
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / metabolism*
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / physiology*
  • Male
  • Middle Aged
  • Receptors, Adiponectin
  • Receptors, Cell Surface / metabolism
  • Recombinant Proteins / pharmacology

Substances

  • ADIPOR1 protein, human
  • ADIPOR2 protein, human
  • Adiponectin
  • Fatty Acids, Nonesterified
  • Insulin
  • Receptors, Adiponectin
  • Receptors, Cell Surface
  • Recombinant Proteins