Intrapancreatic Infusions of the Sulfonylureas

Colwell, John A.; Colwell, Arthur R.

doi:10.2337/diab.6.1.60

Cited by 9 publications

(10 citation statements)

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“…Although this study in no sense contributes to clarification of the problem of its mechanism of action, the results are in harmony with the concept that tolbutamide enhances the release of insulin from the beta cells (2)(3)(4)(5)(6) There is, however, experimental evidence that tolbutamide potentiates the action of exogenous insulin in totally depancreatized animals (11)(12)(13) The rapidity and magnitude of the decline of blood glucose levels which characterize the nondiabetic group are in contrast to the more gradual and occasionally irregular responses of the diabetics.…”

Section: Discussionmentioning

confidence: 78%

“…Indirect evidence of a correlation between tolbutamide responsiveness and pancreatic insulin content (1), coupled with experimental support for the view that the drug stimulates endogenous secretion of insulin (2)(3)(4)(5)(6), suggest that this difference may be of more than empirical interest. The purpose of the following study was to compare response to intravenously administered tolbutamide in nondiabetic and mild diabetic subjects, including those with a normal and near-normal fasting blood glucose level.…”

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confidence: 99%

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Comparison of Response to Intravenously Administered Sodium Tolbutamide in Mild Diabetic and Nondiabetic Subjects12

Unger¹,

Madison²

1958

J. Clin. Invest.

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Section: Discussionmentioning

confidence: 78%

mentioning

confidence: 99%

Comparison of Response to Intravenously Administered Sodium Tolbutamide in Mild Diabetic and Nondiabetic Subjects12

Unger¹,

Madison²

1958

J. Clin. Invest.

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“…preparation of the ketone solutions has been described Pancreatic arterial infusions were carried out according in a previous publication (18). Arterial blood samples to the technique of Colwell, Colwell, and Colwell (24). were collected at 15-to 20-minute intervals during in-Pancreatic venous samples were collected through a fusion and the ensuing hour.…”

Section: Methodsmentioning

confidence: 99%

The Hypoglycemic Action of Ketones. II. Evidence for a Stimulatory Feedback of Ketones on the Pancreatic Beta Cells *

Madison¹,

Mebane²,

Unger³

et al. 1964

J. Clin. Invest.

223

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The effects of alterations in carbohydrate metabolism induced by starvation and insulin deprivation on hepatic ketone production and peripheral ketone utilization have been the subject of intensive investigation (1-12). Only scant attention, however, has been paid to the effects that hyperketonemia, in turn, might have on carbohydrate and fat metabolism. The conflicting results from such studies (13-17) have been reviewed recently (18). Studies in this laboratory, designed to define the effects of induced hyperketonemia on carbohydrate and fat metabolism (18,19), showed that iv infusions of ,8-hydroxybutyric acid, acetoacetic acid, or their sodium salts produced the following immediate changes in glucose and nonesterified fatty acid (NEFA) metabolism: 1) blood glucose concentration fell promptly, at times to distinctly hypoglycemic levels, 2) hepatic glucose output decreased sharply to less than 50% of control values, a reduction accounting entirely for the decrease in arterial glucose concentration, and 3) these changes in glucose metabolism were accompanied simultaneously by a greater than 50% fall in arterial plasma NEFA concentration. The qualitative similarity between ketone infusion and the slow iv administration of insulin (20) only on blood glucose concentration and hepatic glucose output but also on plasma NEFA concentration suggested the possibility that ketones produce these effects via stimulation of endogenous insulin secretion.The present studies were designed specifically to determine whether ketone bodies stimulate the pancreatic 8-cells, directly or indirectly, to secrete increased amounts of insulin. Two types of studies were performed: in the first group, the effects of hyperketonemia produced by infusions of 8-hydroxybutyrate and acetoacetate on blood glucose concentrations were compared in depancreatized dogs and in dogs with alloxan diabetes; in the second group of studies, the changes in pancreatic venous insulin concentrations were determined by immunoassay during infusions of ketones either into a femoral vein or into a branch of the pancreatic artery. MethodsIn the studies designed to compare the effects of ,3-hydroxybutyrate and acetoacetate on the arterial glucose concentration of totally diabetic depancreatized and partially diabetic alloxanized dogs, experiments were performed at least 2 weeks after alloxanization (21)

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“…Also favoring this hypothesis are experiments in dogs utilizing direct perfusion of the pancreas 28 and cross circulation. 29 ' 30 On the other hand, that the pancreas is not essential for the hypoglycemic action of the drugs is demonstrated by the fact that some totally depancreatized dogs maintained on suboptimal amounts of insulin experience a definite lowering of blood and urine glucose when treated chronically with carbutamide.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Canadian and British Experiences with the Sulfonylureas

Ricketts¹

1957

Diabetes

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Intrapancreatic Infusions of the Sulfonylureas

Cited by 9 publications

References 0 publications

Comparison of Response to Intravenously Administered Sodium Tolbutamide in Mild Diabetic and Nondiabetic Subjects12

Comparison of Response to Intravenously Administered Sodium Tolbutamide in Mild Diabetic and Nondiabetic Subjects12

The Hypoglycemic Action of Ketones. II. Evidence for a Stimulatory Feedback of Ketones on the Pancreatic Beta Cells *

Canadian and British Experiences with the Sulfonylureas

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