Adiposity predisposes to insulin resistance and type II diabetes. Adipose tissue is an active endocrine organ, secreting adipokines with important physiological actions. Adiponectin is a recently discovered adipokine whose levels are, paradoxically, decreased in obesity despite the increase in adipocyte mass. Adiponectin suppresses triglyceride accumulation, increases fatty acid oxidation and activates AMP kinase (AMPK) in skeletal muscle, improving insulin signalling, and it suppresses glucose production and activates AMPK in liver. Hence, adiponectin is an insulin sensitizer in skeletal muscle and liver. Our aim here was to investigate the effects of adiponectin on pancreatic β-cell function and, in particular, on AMPK since, in these cells, AMPK activation causes inhibition of insulin secretion. We used MIN6 cells, a murine pancreatic β-cell line. Adiponectin (2 μg/ml) suppressed AMPK activity and caused an increase in insulin secretion. Insulin secretion requires an increase in free cytoplasmic Ca2+([Ca2+]i,), and we examined the effect of acute (30 min) application of adiponectin on [Ca2+]i. Adiponectin caused a prompt increase in [Ca2+]i. The increases in [Ca2+]i and insulin production were prevented by nifedipine, a blocker of L-type Ca2+ channels, and did not occur in Ca2+ free solution. The suppression of AMPK activity and increases in insulin and [Ca2+]i induced by adiponectin were comparable to those evoked by high glucose stimulation (Table).
|Adiponectin (in 3 mM glucose)||48±10% (P=0.01)||303±51% (P=0.001)||142±14% (P=0.03)|
|25 mM Glucose||68±6% (P=0.01)||173±12% (P=0.001)||161±11% (P=0.01)|
In conclusion, adiponectin has a profound direct effect on pancreatic β-cell function. Adiponectin suppresses the activity of AMPK, and increases insulin secretion by increasing [Ca2+]i via influx across the plasma membrane. These results demonstrate that adiponectin can contribute to insulin secretion and reveal its potential as a novel therapeutic target against obesity-linked type II diabetes.
03 - 07 May 2008
European Society of Endocrinology