Pioglitazone increases insulin sensitivity, reduces blood glucose, insulin, and lipid levels, and lowers blood pressure, in obese, insulin-resistant rhesus monkeys.
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.
Kemnitz
J W
JW
Wisconsin Regional Primate Research Center, Madison 53715-1299.
Elson
D F
DF
Roecker
E B
EB
Baum
S T
ST
Bergman
R N
RN
Meglasson
M D
MD
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D004435:Eating; D005215:Fasting; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D005951:Glucose Tolerance Test; D006339:Heart Rate / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood* / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology*; D008253:Macaca mulatta; D008297:Male; D009765:Obesity / Q000097:blood / Q000503:physiopathology*; D000077205:Pioglitazone; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D014044:Tolbutamide / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D013844:Thiazoles; D045162:Thiazolidinediones; D014280:Triglycerides; D014044:Tolbutamide; D000077205:Pioglitazone