Effects of pancreatectomy, tolbutamide and insulin on glucose fluxes in chickens

Abstract

The effects of pancreatectomy and of injection of insulin or Tolbutamide on glucose fluxes in chickens were examined. This was prompted by earlier observations that Tolbutamide seems not to require the presence of pancreatic insulin for its acute hypoglycaemic action in this species. Rates of appearance (Ra) and disappearance (Rd) of glucose were estimated by isotope dilution using [14C]glucose in single-injection experiments and [14C]glucose and [6-3H]glucose in priming-injection + constant-infusion experiments. Six hours after sub-total pancreatectomy (splenic lobe remained in situ), chickens were hyperglycaemic (16.7 v. 10-4 mmol glucose/1 in controls), had a larger sampled glucose pool (4.41 v. 3.10 mmol) and a higher average rate of glucose utilization (41.7 v. 33.3 micron mol/kg per min) than sham-operated controls as estimated in single-injection experiments. Tolbutamide (50 mg/kg injected i.v.) reduced Ra in intact chickens from 33.9 to 1.1 micro mol/kg per min and reduced Ra in pancreatectomized chickens from 42.2 to 10.2 micro mol/kg per min. in priming-injection + constant-infusion experiments tolbutamide again reduced Ra significantly. In all case Rd tended to fall, apparently as a result of the developing hypoglycaemia. tolbutamide did not affect the volume of extracellular fluid (sucrose space). In single-injection experiments , insulin (1 unit/kg injected i.v.) reduced Ra by 56% and transiently increased Rd by 39%. It was concluded that pancreatectomy and injection of insulin or tolbutamide produce responses in glucose movements in chickens that are qualitatively similar to those in mammals. In chickens the hypoglcaemic action of tolbutamide, which persists in the absence of the pancreas, depends on an inhibition of glucose release by the liver.

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].…”

“…Tolbutamide activates glycolytic and glycogenic pathways and inhibits gluconeogenic pathway through regulating key enzyme activities in the liver [38]. Danby et al [17] demonstrated that in pancreatectomized chickens, the hypoglycemic action of tolbutamide depends on an inhibition of glucose release by the liver.…”

“…To examine the relationship of insulin and glucose, broiler embryos were subjected to acute or prolonged hypoglycemia during the late embryonic phase by, respectively, injecting once (at embryonic day [ED] 16 or 17) or on 3 consecutive days (ED 16,17,and 18) with tolbutamide (80 mg/g embryo weight), a substance that stimulates insulin secretion from the pancreas. After 1 tolbutamide injection, a prolonged (32 h) decrease of plasma glucose and a profound acute increase in plasma insulin were observed.…”

“…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.…”

Effect of Tolazamide on Basal Ketogenesis, Glycogenesis, and Gluconeogenesis in Liver Obtained from Normal and Diabetic Rats*

“…Although we investigated only lactate as a glucose precursor, a mechanism for action for tolazamide similar to that for glisoxepide may exist. Also, in pancreatectomized chickens, tolbutamide was capable of attenuating hepatic glucose production, most likely by affecting gluconeogenesis (27). However, other studies can be found in which an insulin-independent sulfonyl-1272 EFFECT OF TOLAZAMIDE ON LIVER Endo • 1986 Volll9«No3 urea effect on hepatic gluconeogenesis was not apparent.…”