INTERACTION OF GLP-I AND LEPTIN AT RAT PANCREATIC B-CELLS - EFFECTS ON INSULIN-SECRETION AND SIGNAL-TRANSDUCTION

The incretin effect is reduced in NIDDM, although a corresponding atte nuation of incretin hormone secretion does not occur. We characterized the direct interaction of GLP-I, an important incretin hormone, and l eptin on insulin secretion and signal transduction in B-cells. Leptin inhibited GLP-I stimulated insulin release from the isolated perfused rat pancreas. Both phases of the biphasic insulin secretory response w ere inhibited. GLP-I receptor binding and GLP-I induced cAMP generatio n remained unchanged. Leptin reduced the GLP-I mediated increase of cy tosolic Ca2+ concentration. It had similar effects on calcium elevatio ns induced by forskolin. The effect was more pronounced during the pla teau phase than during the initial peak. These effects could help to e xplain leptin's inhibitory effects on insulin secretion. The inhibitio n of GLP-I's insulinotropic effects by leptin may be an interesting as pect in the pathophysiology of NIDDM. The existence of an ''adipo-insu lar axis'' is suggested, in which leptin represents a negative feed-ba ck signal from the adipose tissue to the endocrine pancreas.