Indomethacin and aspirin prevent the starvation-induced fall in plasma insulin

To investigate whether prostaglandins (PGs) play a role in the regulation of insulin secretion during starvation, we have studied the effects of two inhibitors of PG synthesis, indomethacin (INDO) and acetylsalicylic acid (ASA), on plasma insulin during a 72-h fast. Five lean males and six obese females were given 200 mg INDO daily throughout a 72-h fast during which plasma glucose was maintained at normal postabsorptive levels by a continuous infusion of glucose. In addition, four obese females were treated with 3 g ASA in a similar protocol. Another six lean males and six obese females served as a control group, receiving only iv glucose during the fast. In both the lean and obese control subjects, a significant decrease in plasma insulin was noted by 72 h (lean, 53 +/- 8% of basal insulin; obese, 69 +/- 6%; P less than 0.02). By contrast, aspirin and INDO administration prevented the decline in plasma insulin in both lean (INDO, 92 +/- 5%) and obese (INDO, 109 +/- 11%; ASA, 111 +/- 17%) subjects. These data suggest that endogenous PG production may be a controlling factor in insulin secretion during starvation.