ROLE OF CAMP IN UP-REGULATION OF INSULIN-SECRETION DURING THE ADAPTATION OF ISLETS OF LANGERHANS TO PREGNANCY

Islets undergo a number of upregulatory changes to meet the increased demand for insulin during pregnancy, including an increase in glucose- stimulated insulin secretion with a reduction in the stimulation thres hold. Treatment with the lactogenic hormone prolactin (PRL) in vitro h as been shown to induce changes in islets similar to those observed du ring pregnancy. We examined cAMP production in islets treated with PRL to determine if changes in cAMP are involved in the upregulation of i nsulin secretion. Insulin secretion and cAMP concentrations were measu red from islets in response to a suprathreshold (6.8 mmol/l) or high ( 16.8 mmol/l) glucose concentration in the presence of the phosphodiest erase inhibitor isobutylmethylxanthine. Insulin secretion increased by 2.1-, 5.0-, and 5.9-fold at the suprathreshold glucose concentration and by 1.6-, 2.3-, and 2.9-fold at the higher glucose concentration af ter 1, 3, and 5 days of PRL treatment, respectively. After a similar p attern, cAMP metabolism increased by 1.2-, 1.6-, and 2.1-fold at the s uprathreshold glucose concentration and by 1.2-, 1.7-, and 2.2-fold at the high glucose concentration after 1, 3, and 5 days of PRL treatmen t, respectively. The similar increases in insulin secretion and cAMP c oncentration suggest that changes in cAMP metabolism are involved in l actogen-induced upregulation of insulin secretion. To gain additional insight into the role of cAMP in the upregulation of islet function af ter lactogen treatment, me examined the relationship between changes i n cAMP concentration and insulin secretion. Under all conditions (diff ering glucose concentrations and time periods), the increase in insuli n release was directly proportional to the increase in cAMP. Thus incr eased glucose-stimulated insulin secretion from lactogen-treated islet s could be accounted for by increased generation of cAMP and did not a ppear to require any further specific changes in intracellular process es mediated by cAMP. Because the PRL receptor is not directly involved in cAMP metabolism, the lactogen-induced increase in cAMP was most li kely due to the increase in glucose metabolism that we have previously demonstrated in PRL-treated islets and in islets during pregnancy.