Suppression of postprandial glucose, insulin, C-peptide, and glucose-dependent insulinotropic peptide (GIP) in man by oral administration of a prostaglandin analogue (enprostil).
Enprostil, a long-acting, orally active dehydroprostaglandin E2 with cytoprotective and gastric antisecretory properties, is a potent inhibitor of meal-stimulated gastrin release. Recent data have suggested suppression of additional other gastrointestinal peptide hormones following single doses of enprostil. The current investigation was conducted to further clarify the effects of enprostil administration on gastrointestinal hormones and glucose metabolism under physiologic conditions and to determine whether these effects were present following multiple doses of the agent. Enprostil 70 mcg/d and its placebo were each administered for 7 1/2 days to eight normal male subjects in a study of crossover design, each treatment period lasting 7 1/2 days and separated by a 7 day washout period. Subjects received a test meal on days 1 and 8 and an oral glucose challenge on day 3 of each treatment period following enprostil or its placebo. Following the test meal, there was a delay and suppression of the maximum measured serum glucose levels. Mean overall peak glucose concentrations were lower during the enprostil phase compared to placebo (112 vs. 121 mg/dd, P = 0.025) with a trend toward delay in the time to achievement of peak glucose concentrations. Mean overall peak levels for insulin, C-peptide, and glucose-dependent insulinotropic peptide (GIP) were significantly suppressed by 36%, 16% and 60%, respectively by enprostil when compared to placebo. The overall integrated postprandial responses for insulin, C-peptide, and GIP were significantly reduced by 42%, 39% and 90%, respectively while that for glucose above baseline was reduced by 44% (P = 0.098). Similar effects were present following the oral glucose challenge.(ABSTRACT TRUNCATED AT 250 WORDS)
Schwartz
K E
KE
Syntex Research, Palo Alto, California.
Zaro
B
B
Reynolds
J
J
Duffy
J
J
Saito
T
T
Hunt
J S
JS
Sevelius
H
H
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis*; D002096:C-Peptide / Q000097:blood*; D016620:Enprostil; D005749:Gastric Inhibitory Polypeptide / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011459:Prostaglandins E, Synthetic / Q000008:administration & dosage / Q000494:pharmacology*
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D011459:Prostaglandins E, Synthetic; D005749:Gastric Inhibitory Polypeptide; D016620:Enprostil