Effects of Acute and Chronic Ingestion of Tolbutamide in the Chicken

Abstract

The effects of acute and chronic ingestion of tolbutamide were studied in the growing chicken. After an oral load of 100 or 25 mg tolbutamide/kg b.w., plasma insulin levels increased in a dose-dependent manner but to relatively low levels for about 10 min, while 10-20 min following tolbutamide, plasma glucose levels were markedly decreased and remained so for 2--5 hr. After 100 mg tolbutamide/kg, the profound hypoglycaemia which developed, was generally accompanied by symptoms resembling an hypoglycaemic coma: panting, muscular flacidity and convulsion. Body temperature and plasma calcium levels were not changed during and after tolbutamide-induced insulin release. In the chicken, tolbutamide response is therefore characterized by a fugitive insulin release and a profound and prolonged hypoglycaemia which suggest that the action of insulin is potentiated by other factors. Chronic ingestion of tolbutamide in the diet transiently (for one week) increased the live body weight of a dose of 400 mg tolbutamide/kg of diet. Long term (5 weeks) fasting plasma glucose levels were unchanged and fasting plasma insulin levels were decreased in the chronic tolbutamide treated chickens.

Prenatal tolbutamide treatment alters plasma glucose and insulin concentrations and negatively affects the postnatal performance of chickens

“…The prolonged hypoglycemic state from 4 h PI to 36 h PI after a single injection of tolbutamide, associated with a profound rise in plasma insulin concentrations at 0.5 h PI, is in agreement with in vitro and in vivo studies on layer and broiler chickens at different ages [9,[14][15][16][17][18][25][26][27][28] and with in vitro and in vivo studies on mice, rats, dogs, and hamsters [29][30][31][32][33]. Indeed, tolbutamide is a potent hypoglycemic agent in mammals and birds and stimulates insulin secretion from pancreatic b-cells, principally by inhibiting adenosine triphosphatesensitive K þ channels in the cell membrane, consequently, causing a membrane depolarization and an activation of voltage-gated Ca 2þ influx [34][35][36].…”

“…The duration of hypoglycemia in tolbutamide-treated broiler embryos was longer than that in tolbutamidetreated broiler chickens in which glucose levels returned back to basal levels almost at 5 h and 8 h after intubation with 100 mg/kg tolbutamide delivered into the crop [16,18]. However, the difference in the duration of hypoglycemia may not depend on the age but might be because of the treatment method (injection vs intubation).…”

“…After injections on ED 16, blood was sampled at 7 time points (16,20,24,28,32,36,and 40 h PI). After injections on ED 17, blood was taken at 4 time points (0.5, 1, 4, and 8 h PI), with 8 eggs per treatment (sham or tolbutamide) per time point.…”

“…In addition, few reports examine the glucose metabolism in chicken specifically during the prenatal period. Tolbutamide is a compound that stimulates insulin secretion from the pancreas [14] and has been successfully used to induce postnatal hypoglycemia in mammals [15] or chickens [9,[16][17][18]. Thorn et al [19,20] have created a hypoglycemia by continuous infusion of intravenous insulin in fetus of ewes for 8 wk during the late pregnancy and suggested that this contributes to embryonic programming of an increased risk for development of uncontrolled hepatic glucose production, hepatic insulin resistance, and diabetes type II in postnatal life.…”