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.
Oral glucose tolerance tests (75 g, 300 ml) were performed in 12 healthy volunteers, with prior administration of placebo, misoprostol (400 micrograms), rioprostil (300 micrograms), enprostil (70 micrograms), or nocloprost (200 micrograms), 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 less than or equal to 0.001) and 45% (P less than or equal to 0.01), respectively, and both gave rise to an initial (approximately 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 less than or equal to 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 less than or equal to 0.05). Enprostil more substantially reduced the integrated incremental response of insulin by 36% (P less than or equal to 0.01), and also reduced the ratio of insulin and C-peptide incremental responses (P less than or equal to 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Nauck
M
M
Department of Medicine, Georg-August-University, Göttingen, FRG.
Härter
S
S
Ebert
R
R
Creutzfeldt
W
W
D000328:Adult; D000527:Alprostadil / Q000494:pharmacology; D004311:Double-Blind Method; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism; D005755:Gastrins / Q000378:metabolism; D005768:Gastrointestinal Hormones / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D016595:Misoprostol; D010187:Pancreatic Hormones / Q000378:metabolism*; D011458:Prostaglandins E / Q000494:pharmacology; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D011897:Random Allocation
D005755:Gastrins; D005768:Gastrointestinal Hormones; D007328:Insulin; D010187:Pancreatic Hormones; D011458:Prostaglandins E; D011459:Prostaglandins E, Synthetic; D016595:Misoprostol; D005749:Gastric Inhibitory Polypeptide; D000527:Alprostadil; D005947:Glucose