The effects of the intestinal glucosidase inhibitory BAY M 1099 (miglitol) on glycemic status of obese-diabetic rats.

1. Groups of lean and obese-diabetic (NIDDM) congenic male SHR/Nutl parallel-cp rats were fed a nutritionally adequate, high carbohydrate diet ad libitum with or without the alpha-glucosidase inhibitor miglitol (150 mg/kg diet) from 8 until 15 weeks of age, and key glycemic parameters were monitored throughout the study. 2. Miglitol treatment resulted in clinical improvement toward normal in percent glycosylated hemoglobin, glycemic and insulinogenic responses to an oral glucose tolerance, and in liver glucokinase activity, in concert with modest decreases in weight gain in obese rats. 3. These observations are consistent with improved insulin sensitivity in peripheral tissues following miglitol treatment, and indicate that this drug may be a useful adjunct to diet in the treatment of obesity, NIDDM, and possibly other disorders of carbohydrate metabolism.

The effects of low-dose Bay-m-1099 (Miglitol) on serum lipids and liver enzyme activity of obese and obese-diabetic corpulent rats.

1. Groups of lean, obese, and obese-non-insulin-dependent diabetic LA/N-cp and SHR/N-cp rats were administered the a-glucosidase inhibitor Miglitol (150 mg/kg diet, ad libitum) from 8 until 15 weeks of age. 2. Phenotype effects (obese greater than lean) were present for weight gain, adiposity, serum glycemic and lipid parameters, and for liver glucokinase, glucose-6-phosphate dehydrogenase, and malic enzyme activity. Miglitol treatment was associated with improvements in glucokinase and malic enzyme in both strains, and in improvements in glycemic parameters in obese rats. 3. These results are consistent with variable improvements in glycemic control and insulin action following low dose Miglitol treatment, and indicate that indirect effects of the drug on insulin sensitivity in peripheral tissues and on glucoregulatory enzymes may contribute to the glycemic improvements observed with this drug, while greater dosages or longer treatment may be required to observe comparable improvements in adiposity or plasma lipid profiles.

Effect of peptide YY on insulin release stimulated by 2-deoxyglucose and neuropeptides in dogs.

Peptide YY (PYY) is a hormone released from gut after a meal. The objective of this study was to determine the effect of PYY on insulin release stimulated by either 2-deoxyglucose (2-DG) or neuropeptides in conscious dogs with gastric and duodenal fistulas. In control experiments dogs received either 2-DG (75 mg/kg i.v. bolus) or atropine (25 micrograms/kg bolus followed by 20 micrograms/kg/h i.v.) plus 2-DG (75 mg/kg i.v.) or bethanechol (80 micrograms/kg/h i.v.) or vasoactive intestinal peptide (VIP, 4 micrograms/kg i.v. bolus) or gastrin-releasing peptide (GRP, 400 pmol/kg/h i.v.) or tetragastrin (G4, 100 micrograms/dog, i.v. bolus). On separate days, PYY was also infused intravenously in combination with one of the above stimulants. Given intravenously, PYY (200, 400 pmol/kg/h) significantly inhibited 2-DG stimulated-insulin secretion in a dose-dependent fashion. This inhibitory effect also existed in the presence of atropine. Peptide YY (400 pmol/kg/h) depressed the insulin levels in response to GRP or G4 but failed to inhibit bethanechol- and VIP-stimulated insulin release. After administration of the above stimulants, PYY did not modify the blood sugar concentrations. These results demonstrated that PYY might inhibit the cephalic phase of insulin release from dogs triggered by 2-DG and by the neuropeptides GRP and G4. Thus, PYY may play a negative feedback regulatory role on insulin release.