Effect of forskolin on islet cyclic AMP, insulin secretion, blood glucose and intravenous glucose tolerance in rats

Abstract

The in vivo effect of forskolin on insulin release, blood glucose and intravenous glucose tolerance test has been studied in the rat. In addition in vitro experiments on the effect of forskolin on islet cAMP and insulin release have been performed for comparison purposes. In batch incubated islets forskolin increased cAMP levels concentration dependently, the EC₅₀ being approximately 25 μM. The maximal effect occurred after 5 min. In the presence of 2.8 mM glucose 10μM forskolin did not stimulate insulin release; however, it potentiated both phase of 11.1 mM glucose induced insulin secretion. I. v. administration of 1.5 mg/kg of forskolin increased blood glocose levels in rats, which was associated with significant elevation of serum insulin. During an i. v. glucose tolerance test forskolin potentiated the insulin releasing capacity of glucose but did not significantly affect blood glucose levels. It is conceivable that cAMP per se does not initiate but rather amplifies insulin release by glucose. Since the synergistic effect of forskolin and glucose on insulin release in vivo is not associated with increased elimination rate it is possible that forskolin exhibits additional effects which counteract the glucose lowering action of insulin.