Comparison of Plasma Insulin Levels Following Administration of Tolbutamide and Glucose

Yalow, Rosalyn S.; Black, Hannah; Villazon, Manuel; Berson, Solomon A.

doi:10.2337/diab.9.5.356

Cited by 211 publications

(65 citation statements)

References 3 publications

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“…The significant increase in insulin levels in portal vein following administration of ouabain in intact animals confirms this interpretation. This would agree with the known effect of insulin on glucose metabolism in the liver and muscle (36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46).…”

Section: Triner Papayoanou Killian Vulliemoz Castany Nahassupporting

confidence: 79%

Effects of Ouabain on Insulin Secretion in the Dog

Triner

Papayoanou

Killian

et al. 1969

Circulation Research

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The mechanism of the previously reported hypoglycemic effect of ouabain was studied in dogs. Ouabain (1.0 /xg/kg/min infused intravenously for 60 minutes) combined with insulin or propranolol caused a greater and more prolonged decrease in blood glucose than either of the drugs administered separately. In intact dogs, ouabain changed significantly portohepatic venous differences in plasma glucose from +6.6 to -13.6 mg/100 ml and in K + from -0.03 to -0.4 mEq/liter. In pancreatectomized animals, ouabain did not cause any significant decrease in peripheral glucose level, and the portohepatic differences in plasma glucose changed from +5.3 to +30.2 mg/100 ml and the differences in K + from -0.01 to +0.2 mEq/liter. These changes, indicating an increased release of glucose and K + by the liver in the pancreatectomized dog, were also observed in isolated rat liver perfused with ouabain 10~6M. Glucose uptake of the hindlimb increased significantly during the infusion of ouabain in normal dogs, but did not change in pancreatectomized dogs. Ouabain caused a significant increase in plasma insulin in portal blood ( + 155%). These results demonstrate that the observed metabolic effects of ouabain in the dog are mainly mediated by insulin and that ouabain increases the secretion of insulin in intact dogs.ADDITIONAL KEY WORDS hypoglycemia potassium cardiac glycosides glucose uptake insulin levels• The metabolic effects of ouabain in different tissues have been extensively studied in vitro. It has been observed that ouabain decreases the formation of lactate and oxidation of glucose and increases glycogen content in the muscle (1-6). Other investigators showed that in adipose tissue hormoneinduced lipolysis was inhibited by ouabain (7-9). The effect of ouabain on epinephrinestimulated glycogenolysis and lipolysis was further studied in this laboratory, and it was Dr. Triner is a Senior Investigator of the New York Heart Association, and Dr. Killian holds U. S. Public Health Service Grant TIAM-5397.Received May 1, 1969. Accepted for publication June 12, 1969. shown that ouabain in vitro inhibits the metabolic effects of epinephrine (10, 11). All these in-vitro studies were performed with 10~r' M to K H M concentrations of ouabain.To study the metabolic effects of ouabain in vivo, experiments were performed in dogs which were given ouabain, 1.0 /i,g/kg/min iv for 60 minutes (12), a substantially lower dose than that used in vitro. This dose, which corresponds approximately to four times the therapeutic dosage, did not produce any marked electrocardiographic or plasma potassium changes, but caused a significant decrease in glucose and glycerol plasma concentrations. The same dose of ouabain significantly inhibited the lipolytic and glycogenolytic effects of epinephrine (12). The purpose of the present series of experiments was to investigate the mechanism of the hypoglycemic effect of ouabain, i.e., to establish whether it is a direct effect of the drug on glucose metabolism or whether it is mediated through insulin.

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Section: Triner Papayoanou Killian Vulliemoz Castany Nahassupporting

confidence: 79%

Effects of Ouabain on Insulin Secretion in the Dog

Triner

Papayoanou

Killian

et al. 1969

Circulation Research

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“…The initial hypoglycemic effect of oral sulfonylurea administration appears to rely on the acute stimulation of-the rate of insulin release from the pancreas (Yalow et al [1]). At the molecular level sulfonylureas are proposed to stimulate insulin secretion by binding to a receptor protein of the plasma membrane of pancreatic/3-cells (for reviews, see [2,3]).…”

Section: Introductionmentioning

confidence: 99%

Differential interaction of glimepiride and glibenclamide with the β-cell sulfonylurea receptor I. Binding characteristics

Müller

Hartz

Pünter

et al. 1994

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Glimepiride is a novel sulfonylurea drug for treatment of non-insulin-dependent diabetes mellitus with higher blood sugar lowering efficacy in diabetic patients than glibenclamide raising the question whether this characteristics is in line with different binding of glimepiride and glibenclamide to the 0-cell sulfonylurea receptor. Scatchard plot analysis of [3H]sulfonylurea binding to membranes isolated from rat 0-cell tumors and (RINm5F) insulinoma cells and to RINm5F cells demonstrated that glimepiride has a 2.5-3-fold lower affinity than glibenclamide. This corresponded well to the 8-9-fold higher kof f and 2.5-3-fold higher kon rates of glimepiride compared to glibenclamide as revealed by the dissociation and association kinetics of [3H]sulfonylurea binding and the K d values calculated thereof. In agreement, the concentrations required for half-maximal displacement of [3H]sulfonylurea bound to 0-cell membranes were significantly higher for glimepiride compared to glibenclamide. However, the binding affinity of glimepiride measured by both equilibrium binding and kinetic binding studies upon solubilization of 0-cell tumor membranes and RINm5F cell membranes increased up to the value for glibenclamide. This was primarily based on a drastic decrease of the dissociation rate constant of glimepiride whereas the kinetics of glibenclamide binding remained largely unaffected upon solubilization. These data suggest that the K d value alone is not sufficient for characterization of a suifonylurea drug, since the kinetic binding parameters may also determine its acute blood sugar lowering efficacy.

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“…It is known that sulphonylureas like Glimepiride, produce hypoglycemia by increasing the secretion of insulin from the pancreas and these compounds are active in mild Streptozotocin-induced diabetes whereas they are inactive in intense Streptozotocin diabetes (nearly all b-cells have been destroyed) (Yallow et al, 1960;Grodsky et al, 1971). Since our results showed that Glimepiride reduce the blood glucose levels in hyperglycemic animals, so it can be postulated that the state of diabetes was not severe.…”

Section: Effects Of Stevia Leaves and Glimepiride (Amaryl®) On Body Wmentioning

confidence: 99%

Comparative efficacy of powdered form of stevia (<i>Stevia rebaudiana</i> Bertoni) leaves and glimepiride in induced diabetic rats

Sumon

Mostofa

Jahan

et al. 1970

Bangl. J. Vet. Med.

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Now a day, various medicinal plants are becoming popular for the treatment of different diseases. Some medicinal plants are being used for the treatment of diabetes all over the world. The study was conducted to investigate the effects of powdered form of Stevia (Stevia rebaudiana Bertoni) leaves on blood glucose concentration and body weight in Streptozotocin induced diabetic rats and for its efficacy study with a patent drug, Glimepiride. The effects of powdered form of Stevia leaves was evaluated in the Streptozotocin (STZ; 55 mg/kg body weight as single intraperitoneal injection) induced diabetic rats and for this, powdered form of Stevia leaves was orally administered at three different dose rates of 150 mg/kg, 200 mg/Kg and 250 mg/Kg body weight, respectively once a day for 3 weeks. Changes in the blood glucose levels and body weights were measured and the data obtained were compared with that of Glimepiride statistically by using Student's unpaired t-test. The powdered form of Stevia leaves produced significant (p<0.01 or p<0.05) hypoglycemic effects on Streptozotocin induced diabetic rats in comparison with that of the standard drug, Glimepiride. Powdered form of Stevia leaves at a dose rate of 250 mg/Kg decreased body weight significantly (p<0.01 or p<0.05) in STZ-induced diabetic rats. From this study, it was observed that powdered form of Stevia leaves possessed both hypoglycemic and body weight reducing effects.

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Comparison of Plasma Insulin Levels Following Administration of Tolbutamide and Glucose

Cited by 211 publications

References 3 publications

Effects of Ouabain on Insulin Secretion in the Dog

Effects of Ouabain on Insulin Secretion in the Dog

Differential interaction of glimepiride and glibenclamide with the β-cell sulfonylurea receptor I. Binding characteristics

Comparative efficacy of powdered form of stevia (<i>Stevia rebaudiana</i> Bertoni) leaves and glimepiride in induced diabetic rats

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