Potentiation of insulin action on the liver by tolbutamide

Colwell, Arthur R.

doi:10.1016/0026-0495(64)90150-7

Cited by 26 publications

(10 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…16 Hypoglycemia occurring one to three-and-one-half hours after combined tolbutamide and insulin infusion into the portal vein may be explained by the agents' potentiation of the subsequent endogenous insulin in the liver. 17 Similarly, glyburide-induced hypoglycemia may ployed in our experimental dogs, produced a slight (15 per cent) fall in blood glucose in one hour which is comparable to the 20 per cent shown in the data. 18 An amount ten times that much caused up to sixfold increase in peripheral venous plasma insulin in dogs with a 35 per cent reduction in blood glucose, both maximal at thirty to sixty minutes after injection.…”

Section: Discussionsupporting

confidence: 80%

Profile of Insulin Release Due to Intrapancreatic Glyburide Infusion

Colwell

Zuckerman

1972

Diabetes

View full text Add to dashboard Cite

Intrapancreatic glyburide infusion in dogs (0.02 nig. per kg. of body weight) for five minutes provoked immediate, marked insulin release into the portal venous blood. Compared to control animals, the normal intrinsic insulin levels were exaggerated at intervals of approximately eighty minutes. Lack of immediate hypoglycemia suggests that the insulin release is merely secondary in contributing to the antidiabetic property of this agent. An amount of tolbutamide fifty times as great caused a weak, delayed insulin response. The delayed blood glucose response is probably caused by the combined action of glyburide and circulating insulin. DIABETES 27:209-15, April, 1972. The major antidiabetic property of the sulfonylureas, to produce hypoglycemia, is thought to be caused by stimulation of insulin secretion. Intravenous infusion of tolbutamide enhanced peripheral plasma venous insulin levels and reduced blood glucose in both humans 1 and dogs. 2 -3 The newest and most potent derivative, glybenzcyclamide, likewise provoked pancreatic venous insulin output and hypoglycemia within one-half hour. 4 These studies failed to prove that this agent directly stimulated the pancreatic islets, since some intermediary action might have been involved, and did not correlate the kinetics of insulin secretion with existing glucose concentration. Therefore, our study was designed to localize the magnitude of the direct stimulus of this new drug to the pancreas, and to compare the chronological sequence of insulinemic and glycemic responses with the effect of its parent compound, tolbutamide. METHODSMongrel dogs weighing 15 to 22 kg. were anesthetized intravenously with sodium Nembutal. For pancreatic infusion, a polyethylene catheter was inserted into the From the Departments of Medicine, Evanston Hospital, Evanston, and Northwestern University Medical School, Chicago, Illinois. right gastroepiploic artery, so that the pancreaticoduodenal artery was perfused by the technic described previously. 5 " 7 A second tube was threaded via a mesenteric vein to a point in the portal vein beyond the entrance of the pancreaticoduodenal vein. This allowed us to determine the effect of a five-minute infusion of the experimental agent on insulin efflux from the pancreas. The glybenzcyclamide* was dissolved with a small amount of 1 N NaOH in alcohol and water (1 part in 100) and made up with saline to a concentration of 0.1 mg. per ml. Dose was 0.02 mg. per kg. of body weight, and rate of infusion was 1 ml. per min. Pancreas-injected controls received the same vehicle but the glybenzcyclamide was omitted. Other dogs received tolbutamide, 1 mg. per kg. of body weight, in a concentration of 5 mg. per ml. of saline for a mean dose of 20 mg. Blood samples were withdrawn from the femoral artery and portal vein fifteen and two minutes before, and at intervals of five to thirty minutes after infusion for four hours. Frozen plasma was stored at -io° to -20 0 C. prior to analysis. Immunoreactive insulin 8 and glucose 9 were determined in duplicate.

show abstract

Section: Discussionsupporting

confidence: 80%

Profile of Insulin Release Due to Intrapancreatic Glyburide Infusion

Colwell

Zuckerman

1972

Diabetes

View full text Add to dashboard Cite

show abstract

“…This effect might be comparable to that of the sulfonylureas, which have been shown in our laboratory to increase peripheral hypoglycemia from intraportal infusion of insulin. 21 Pensuwan et al 22 demonstrated a fall in glucose output from rat liver slices and perfused rat liver with addition of leucine. This was not altered by infusion of insulin.…”

Section: Discussionmentioning

confidence: 98%

“…Intraportal infusion of an amount of tolbutamide twice that employed in the present experiments (100 mg.) reduced the peripheral venous blood glucose less than 10 per cent. 21 Since the smaller dose caused the blood glucose to drop 25 per cent in the presence of leucine, the latter agent may influence the liver as well as pancreatic function. The hypoglycemia from leucine could not be demonstrated in humans given insulin infusions.…”

Section: Discussionmentioning

confidence: 99%

Hypoglycemia Due to Intrapancreatic Infusion of Leucine

Colwell

1966

Diabetes

View full text Add to dashboard Cite

Introduction of L-leucine (0.2 gm.) in saline into the pancreatic artery in anesthetized dogs pretreated with chlorpropamide caused a marked peripheral venous hypoglycemia. Intraportal administration of leucine to sensitized dogs failed to produce the effect, as did injection of leucine or tolbutamide separately into the pancreas in the absence of pretreatment. Fall in blood glucose caused by infusion of leucine and tolbutamide concurrently into the pancreatic artery was not significantly different from that due to infusion into the portal vein.The hypoglycemia is most likely due to insulin secretion from pancreatic islets sensitized by action of chlorpropamide to the stimulating effect of leucine. Intraportal infusion of tolbutamide and leucine produced a greater fall in venous blood glucose than a doubled amount of tolbutamide alone. This might support the idea of a second action of leucine that might enhance the effect of endogenous insulin on the liver. DIABETES 75:560-64, August, 1966.

show abstract

“…(Endocrinology 119: [1268][1269][1270][1271][1272][1273]1986) T HE AMELIORATION by sulfonylureas of the disturbed glucose and fatty acid metabolism associated with diabetes is due in part to poorly understood postreceptor cellular mechanisms (1)(2)(3)(4)(5). Numerous in vitro and in vivo investigations have revealed enhanced insulin action in the presence of these drugs, such as the augmentation of hepatic glycogen synthesis (6,7), lipogenesis (8), adipocyte hexose transport (9), and peripheral glucose disposal (10) and the attenuation of hepatic glucose production (11,12). However, if these studies were done under basal, i.e.…”

mentioning

confidence: 97%

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

et al. 1986

View full text Add to dashboard Cite

The effect of tolazamide on in vitro rates of gluconeogenesis, ketogenesis, and glycogenesis was determined in liver tissue from fasted normal and diabetic rats. Hormones were not added to the incubation mixture. Two concentrations of the drug were tested, one of which was therapeutic (40 micrograms/ml) and other immoderately elevated (400 micrograms/ml). Neither drug concentration affected hepatic glycogen synthesis. However, the low dose of tolazamide inhibited ketogenesis in the diabetic liver by 39% and in the control liver by 32%; oxidative CO2 production from palmitate was reduced in parallel with ketogenesis. The drug did not alter ketogenesis in isolated intact mitochondria. Similarly, this same therapeutic dose curtailed hepatic gluconeogenesis only in control liver (74% inhibition); this reaction was unaltered by this drug concentration in the explants derived from the diabetic rats. The logarithmically higher dose inhibited hepatic gluconeogenesis in both control and diabetic liver tissue by 56% and 51%, respectively. Hence, possibly acting at a postreceptor site, therapeutic concentrations of tolazamide can decrease rat hepatic in vitro gluconeogenesis and ketogenesis.

show abstract

Potentiation of insulin action on the liver by tolbutamide

Cited by 26 publications

References 26 publications

Profile of Insulin Release Due to Intrapancreatic Glyburide Infusion

Profile of Insulin Release Due to Intrapancreatic Glyburide Infusion

Hypoglycemia Due to Intrapancreatic Infusion of Leucine

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

Contact Info

Product

Resources

About