Adiponectin induces insulin secretion in vitro and in vivo at a low glucose concentration

Diabetologia. 2008 May;51(5):827-35. doi: 10.1007/s00125-008-0944-9. Epub 2008 Mar 28.

Abstract

Aims/hypothesis: A decrease in plasma adiponectin levels has been shown to contribute to the development of diabetes. However, it remains uncertain whether adiponectin plays a role in the regulation of insulin secretion. In this study, we investigated whether adiponectin may be involved in the regulation of insulin secretion in vivo and in vitro.

Methods: The effect of adiponectin on insulin secretion was measured in vitro and in vivo, along with the effects of adiponectin on ATP generation, membrane potentials, Ca2+ currents, cytosolic calcium concentration and state of 5'-AMP-activated protein kinase (AMPK). In addition, insulin granule transport was measured by membrane capacitance and total internal reflection fluorescence (TIRF) analysis.

Results: Adiponectin significantly stimulated insulin secretion from pancreatic islets to approximately 2.3-fold the baseline value in the presence of a glucose concentration of 5.6 mmol/l. Although adiponectin had no effect on ATP generation, membrane potentials, Ca2+ currents, cytosolic calcium concentrations or activation status of AMPK, it caused a significant increase of membrane capacitance to approximately 2.3-fold the baseline value. TIRF analysis revealed that adiponectin induced a significant increase in the number of fusion events in mouse pancreatic beta cells under 5.6 mmol/l glucose loading, without affecting the status of previously docked granules. Moreover, intravenous injection of adiponectin significantly increased insulin secretion to approximately 1.6-fold of baseline in C57BL/6 mice.

Conclusions/interpretation: The above results indicate that adiponectin induces insulin secretion in vitro and in vivo.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Adiponectin / pharmacology*
  • Animals
  • Cyclic AMP / metabolism
  • Electrophysiology
  • Glucose / pharmacology*
  • Glycolysis
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / cytology
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Islets of Langerhans / physiology
  • Membrane Potentials / physiology
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence
  • Palmitic Acid / metabolism

Substances

  • Adiponectin
  • Insulin
  • Palmitic Acid
  • Adenosine Triphosphate
  • Cyclic AMP
  • Glucose