The effects of prostacyclin (PGI2) and its degradation product 6-keto-prostaglandin F1α (6-keto-PGF1α) on insulin secretion and cyclic adenosine 3′, 5′-monophosphate (cAMP) production were investigated in isolated rat islets. At a glucose concentration of 5.6 mM, addition of both PGI2 and 6-keto-PGF1α in a concentration range of 10−8–10−4 M significantly stimulated insulin secretion. The effects were concentration dependent, being maximal at an initial PGI2 concentration of 10−6M (2.7-fold increase, P < 0.001) and an initial 6-keto PGF1α concentration of 10−7 M (2.1-fold increase, P < 0.005). Lesser stimulation was observed at higher concentrations of both agents. In contrast to their relative effects on insulin secretion, PGI2 was approximately 100-fold more potent at increasing islet cAMP content.and higher concentrations were progressively more effective in raising islet cAMP content.
The effect of PGI2 on insulin secretion was dependent on the medium glucose concentration. At an initial PGI2 concentration of 40 μM, significant stimulation of insulin secretion was seen at glucose concentrations of 3.3 and 5.6 mM, but no effect was seen either in the absence of glucose, or at high glucose concentrations (10 and 16.7 mM). In contrast to the glucose dependency of the effect of PGI2 on insulin secretion, it caused a comparable increase in islet cAMP content at all glucose concentrations tested.
In the presence of 0.5 mM 3-isobutyl-1-methylxanthine (IBMX), PGI2 inhibited insulin secretion at glucose concentrations of 5.6–16.7 mM. However, in this situation PGI2 caused a further increase in islet cAMP above that found with IBMX alone. It is concluded that both PGI2 and 6-keto-PGF1α affect insulin secretion in vitro, although the effects of PGI2 may depend on its conversion to 6-keto-PGF1α. The effects of PGI2 can be either stimulatory or inhibitory, depending on the concentrations of glucose and IBMX in the medium, and cannot be explained solely by its effect on islet cyclic AMP content.