Effect of tyrosine kinase inhibitors on islets of Langerhans: evidence for tyrosine kinases in the regulation of insulin secretion.

In order to determine if tyrosine kinase activation is involved in the changes in islet function, the effect of tyrosine kinase inhibitors on insulin secretion and islet cell proliferation was examined in cultured islets of Langerhans. When islets were exposed to 100 microM genistein or 2 microM herbimycin A, large 5- to 10-fold increases in insulin secretion were observed. The effect on insulin secretion was detected within 1 hr and was maintained for at least 4 days. The glucose sensitivity of islets exposed to genistein was dramatically increased as demonstrated by a shift of the glucose-dose response curve to lower glucose concentrations. In contrast, islet cell proliferation was dramatically reduced in the presence of these tyrosine kinase inhibitors in the absence or presence of PRL. These very large changes observed in islets suggest that tyrosine kinases may have important roles in the regulation of beta-cell function.