Persistent hypoglycemia is induced by tolbutamide administration in broiler chickens fed a low-carbohydrate diet

With a view to gaining an insight into the regulatory mechanism of blood glucose concentrations specific to the chicken, an experimental induction of hypoglycemia was conducted by single or sequential administration of tolbutamide in broiler chickens fed a standard or low-carbohydrate diet. A single dosing of tolbutamide at levels of 25-200 mg/kg body weight decreased plasma glucose concentrations for 2 to 8 h after the dosing in chickens fed either diet. No significant rise in plasma insulin concentration was observed for 2 to 24 h after the single dosing of tolbutamide in chickens on either diet, with the exception of a significant rise when chickens on the standard diet received 100 mg tolbutamide. However, a transient increase of plasma insulin concentration was observed only in the 20 min immediately after the single dosing. Persistent hypoglycemia that was sustained for 5 days, with no significant changes in plasma insulin concentration, was induced by sequential dosing (3 times per day for 5 days, every 8 h) of tolbutamide (100 and 200 mg/kg body weight) in chickens fed the low-carbohydrate diet. In these chickens, the consistently low concentration of plasma glucose, with small diurnal variations, was evidenced by the determination of plasma glucose every 3 h in day 4/5 of the tolbutamide dosing. In chickens fed the standard diet, on the other hand, the low plasma glucose concentrations for 5 days were accompanied by significant diurnal fluctuations. Chickens with persistent hypoglycemia showed slight decreases in plasma non-esterified fatty acids (NEFA) concentration and only slight changes in blood D-3-hydroxybutyrate (3HB) concentration. The present study shows that the persistent hypoglycemia with normoinsulinemia, in the main, is induced by tolbutamide dosing in chickens fed a low-carbohydrate diet, and that the blood concentrations of NEFA and 3HB, alternatives of energy source in animals, are only slightly changed or not at all in hypoglycemic chickens.