Effect of Enprostil on Plasma Glucose, Insulin and Lipid Metabolism in Patients with Non-Insulin-Dependent Diabetes Mellitus

Reaven, Gerald M.; Swislocki, Arthur L; Jeng, Chii; Hollenbeck, C. B.; Schwartz, Kenneth E.; Chen, Y. D I

doi:10.1055/s-2007-1010903

Cited by 9 publications

(11 citation statements)

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“…GIP is a member of the secretin-glucagon family and is a very potent stimulator of insulin release and may be the major mediator of the enleroinsular axis. While some reports describe an inhibition of insulin and GIP [37], others have found the converse [38] or no change in insulin, but a decrease in GIP [39]. Decreased GIP levels have recently been reported after misoprostol administration to human volunteers [40], No significant effects on insulin or GIP were ob served in the present study.…”

Section: Discussioncontrasting

confidence: 50%

Plasma and Tissue Hormones in the Dog after Administration of the Prostaglandin Analogue, Misoprostol

Goodlad

Ghatei²,

Bloom³

et al. 1992

Digestion

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Dogs were given a prostaglandin analogue, misoprostol, at a dose that significantly increases gastrointestinal epithelial cell proliferation. Both basal and postprandial concentrations of gastrin were significantly higher in the misoprostol-treated dogs and more than doubled after the meal in both the controls and in the test group. Plasma enteroglucagon, cholecystokinin, insulin and glucose-dependent insulinotrophic peptide all increased postprandially, with no effect of misoprostol. Tissue concentrations of bombesin, gastrin and somatostatin were unaffected by misoprostol, but the fundic gmcagon-like immunoreactivity was significantly increased. Thus high doses of misoprostol have only minor effects on gastrointestinal regulatory peptides, suggesting that the trophic effect of prostaglandins on the intestinal tract may be direct.

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Section: Discussioncontrasting

confidence: 50%

Plasma and Tissue Hormones in the Dog after Administration of the Prostaglandin Analogue, Misoprostol

Goodlad

Ghatei²,

Bloom³

et al. 1992

Digestion

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“…In vitro [5–11] studies have shown that prostaglandins of the E series improve both glucose transport and glycogen synthesis in muscle, adipocytes and hepatocytes. Acute infusion of PGE1 into the human forearm also has been shown to augment glucose uptake [15–17] and chronic oral administration of synthetic analogues of PGE1 and PGE2 in type‐2‐diabetic patients has been shown to improve glycaemic control [18–20]. It is surprising therefore that no previous study has examined the effects of PGE1 on insulin sensitivity in man.…”

Section: Discussionmentioning

confidence: 99%

“…Based upon previous in vitro [5–12] and in vivo [15–20] studies, we were surprised by the lack of any stimulatory effect of acute misoprostol (PGE1) administration on whole body insulin‐mediated glucose disposal. As all of the major pathways of glucose disposal (glycogen synthesis, glycolysis, glucose oxidation) were examined in the present study (table 2), we do not believe that an insulin‐sensitizing effect on one pathway could have been obscured by a reciprocal decrease in another glucose metabolic pathway.…”

Section: Discussionmentioning

confidence: 99%

Effect of misoprostol (PGE1) on glucose metabolism in type‐2‐diabetic and control subjects

Lee¹,

Matsuda

Bressler

et al. 2002

Diabetes Obesity Metabolism

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In vitro and in vivo studies have demonstrated that prostaglandins of the E series enhance muscle glucose uptake. We examined the effect of acute misoprostol (PGE1) administration on whole body insulin-mediated glucose disposal, as well as the major intracellular pathways of glucose metabolism in type 2 diabetic (n = 10) and non-diabetic (n = 4) subjects. Each subject received two 240-min euglycaemic insulin (40 mU/m2/min) clamp studies with tritiated glucose and indirect calorimetry. During one of the insulin clamp studies, 200 microg of misoprostol was ingested at 90 and 150 min after the start of the insulin infusion. Insulin-mediated total body glucose disposal, glycolysis, glycogenesis and glucose oxidation were similar during the insulin clamp studies performed without and with misoprostol in both the diabetic and non-diabetic groups. These results demonstrate that the acute administration of misoprostol does not enhance insulin-mediated glucose disposal in either type-2-diabetic or non-diabetic subjects.

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“…Other agents that potentially augment GLP-1 release It has been noted that, in healthy subjects, enprostil (a prostaglandin E2 analogue) is able to almost completely prevent the increment in gastric inhibitory polypeptide (GIP) (Nauck et al, 1991, Nicholl et al, 1991. Since GIP probably is the most important incretin hormone in healthy man (which considerably contributes to glucose-or meal-induced insulin secretion (Nauck et al l993a), it was a surprise that the absence of a GIP response after oral glucose did not reduce insulin secretory responses or deteriorate glucose tolerance (Reaven et al, 1988;Nauck et al, 1991;Nicholl et al, 1991). One obvious explanation would be a compensatory increment in the other known incretin, GLP-1.…”

Section: Glp-1 In the Lower Gut: Enough To Treat Type 2-diabetes By Mmentioning

confidence: 99%

Glucagon-like peptide 1 (GLP-1) as a new therapeutic approach for Type 2-diabetes

Nauck

Holst

Willms

et al. 2009

Exp Clin Endocrinol Diabetes

132

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Glucagon-like peptide 1 (GLP-1) is a physiological incretin hormone in normal humans explaining in part the augmented insulin response after oral versus intravenous glucose administration. In addition, GLP-1 also lowers glucagon concentrations, slows gastric emptying, stimulates (pro)insulin biosynthesis, reduces food intake upon intracerebroventricular administration in animals, and may, in addition, enhance insulin sensitivity. Therefore, GLP-1, in many aspects, opposes the Type 2-diabetic phenotype characterized by disturbed glucose-induced insulin secretory capacity, hyperglucagonaemia, moderate insulin deficiency, accelerated gastric emptying, overeating (obesity) and insulin resistance. The other incretin hormone, gastric inhibitory polypeptide (GIP), has lost almost all its activity in Type 2-diabetic patients. In contrast, GLP-1 glucose-dependently stimulates insulin secretion in diet- and sulfonylurea-treated Type 2-diabetic patients and also in patients under insulin therapy long after sulfonylurea secondary failure. Exogenous administration of GLP-1 ([7-37] or [7-36 amide]) in doses elevating plasma concentrations to approximately 3-4 fold physiological postprandial levels fully normalizes fasting hyperglycaemia in Type 2-diabetic patients. The half life of GLP-1 is too short to maintain therapeutic plasma levels for sufficient periods by subcutaneous injections. Current research activities aim at finding GLP-1 analogues with more suitable pharmacokinetic properties than the original peptide. Another approach could be the augmentation of endogenous release of GLP-1, which is abundant in L cells of the lower small intestine and the colon. Interference with sucrose digestion using alpha-glucosidase inhibition moves nutrients into distal parts of the gastrointestinal tract and, thereby, prolongs and augments GLP-1 release. Enprostil, a prostaglandin E2 analogue, fully suppresses GIP responses, while only marginally affecting insulin secretion and glucose tolerance after oral glucose, suggesting compensatory hypersecretion of additional insulinotropic peptides, possibly including GLP-1. Given the large amount of GLP-1 present in L cells, it appears worthwhile to look for more agents that could 'mobilize' this endogenous pool of the 'antidiabetogenic' gut hormone GLP-1.

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Effect of Enprostil on Plasma Glucose, Insulin and Lipid Metabolism in Patients with Non-Insulin-Dependent Diabetes Mellitus

Cited by 9 publications

References 0 publications

Plasma and Tissue Hormones in the Dog after Administration of the Prostaglandin Analogue, Misoprostol

Plasma and Tissue Hormones in the Dog after Administration of the Prostaglandin Analogue, Misoprostol

Effect of misoprostol (PGE1) on glucose metabolism in type‐2‐diabetic and control subjects

Glucagon-like peptide 1 (GLP-1) as a new therapeutic approach for Type 2-diabetes

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