Effects of four orally administered analogues of prostaglandin E1 and E2 on glucose tolerance and on the secretion of pancreatic and gastrointestinal hormones in man

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Abstract
Oral glucose tolerance tests (75 g, 300 ml) were performed in 12 healthy volunteers, with prior administration of placebo, misoprostol (400 μg), rioprostil (300 μg), enprostil (70 μg), or nocloprost (200 μg), in a double‐blind, randomized manner. None of the drugs significantly affected glucose tolerance, although with misoprostal some volunteers displayed an impaired glucose tolerance. Nocloprost was without effect on gastric inhibitory polypeptide (GIP) and did not influence insulin or C‐peptide concentrations. Misoprostol and rioprostil reduced integrated incremental responses of GIP by 57% (P± 0.001) and 45% (P± 0.01), respectively, and both gave rise to an initial (˜10 min) delay of insulin and C‐peptide responses, without a significant overall reduction in integrated incremental responses. Enprostil almost totally inhibited the GIP response (by 94%; P± 0.001), delayed initial insulin and C‐peptide responses, but reduced the integrated incremental C‐peptide response (which corresponds to the overall release of insulin) by only 14% (P± 0.05). Enprostil more substantially reduced the integrated incremental response of insulin by 36% (P± 0.01), and also reduced the ratio of insulin and C‐peptide incremental responses (P± 0.001). In conclusion, prostaglandin E analogues which caused a reduction in GIP responses, and thereby disrupting the enteroinsular axis to varying degrees, delayed the time‐course of insulin secretion without a significant impact on glucose tolerance. Only enprostil, moderately, reduced overall insulin secretion, and, furthermore, reduced insulin in the peripheral circulation relative to the amount of insulin (C‐peptide) secreted. This phenomenon is most likely explained by an increased insulin clearance from the circulation under the influence of enprostil.