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Pioglitazone increases insulin sensitivity, reduces blood glucose, insulin, and lipid levels, and lowers blood pressure, in obese, insulin-resistant rhesus monkeys

Diabetes. 1994 Feb;43(2):204-11. doi: 10.2337/diab.43.2.204.

Abstract

The antidiabetic effects of pioglitazone hydrochloride were evaluated in 6 spontaneously obese, insulin-resistant rhesus monkeys. The animals were studied during six successive 2-wk treatment phases separated by 2-wk rest periods: two placebo phases; 0.3, 1.0, and 3.0 mg.kg-1 x day-1 pioglitazone hydrochloride phases; and a final placebo phase. During the second week of each treatment phase, serum insulin (immunoreactive insulin [IRI]), plasma glucose, and serum triglyceride (TG) levels were measured after an overnight fast and after a standardized meal. Blood pressure was measured and glucose tolerance tests (modified minimal model protocol) were performed a few days after the meal tests. Pioglitazone hydrochloride significantly improved fasting and postprandial levels of IRI, plasma glucose, and TG in a dose-related manner (P < 0.05). Fasting values during treatment with 3.0 mg.kg-1 x day-1 were reduced by 64% for IRI, 19% for plasma glucose, and 44% for TG compared with the placebo phase before treatment. Efficacy of pioglitazone hydrochloride was more marked for those animals with fasting hyperglycemia. Insulin sensitivity was increased by pioglitazone hydrochloride (P = 0.05), whereas glucose effectiveness and glucose disappearance rate were not detectably affected. Systolic and mean arterial blood pressures were significantly decreased by pioglitazone hydrochloride (P < 0.05). No toxic side effects of pioglitazone hydrochloride treatment were noted.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism*
  • Blood Pressure / drug effects*
  • Body Weight / drug effects
  • Eating
  • Fasting
  • Feeding Behavior / drug effects
  • Female
  • Glucose Tolerance Test
  • Heart Rate / drug effects
  • Hypoglycemic Agents / pharmacology*
  • Insulin / blood*
  • Insulin / pharmacology*
  • Insulin Resistance / physiology*
  • Macaca mulatta
  • Male
  • Obesity / blood
  • Obesity / physiopathology*
  • Pioglitazone
  • Thiazoles / pharmacology*
  • Thiazolidinediones*
  • Tolbutamide / pharmacology
  • Triglycerides / blood*

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Thiazoles
  • Thiazolidinediones
  • Triglycerides
  • Tolbutamide
  • Pioglitazone