Insulin Secretion Following Carbutamide Injections in Normal Dogs.

Abstract

539developed about the same aortic sensitivity as males. In comparison to females, castration did not have much effect on males, since little difference was noted when the aortae of operated animals were compared to normal ones. Likewise, the salt diet did not increase aortic responsiveness to epinephrine in castrated males beyond that found in normal males. These findings indicate that the presence of female sex hormones is required to maintain a low reactivity to epinephrine in the aorta. Removal of the male hormone, on the other hand, did not change the reactivity of the aorta, nor sensitize the animal to the salt diet. The mechanism whereby the salt diet increases the reactivity of vessel strips to epinephrine may be explainable by the theory of Raab ( 5 ) that increased intracellular sodium in smooth muscle of blood vessels potentiates the constrictor effects of epinephrine, possibly by raising the membrane electrical potentials of muscle cells upon which catecholamines act.Summary. Strips were prepared from aortae of rats and their reactivity to epinephrine tested by means of a lever system that recorded shortening of the smooth muscle. A 2% salt diet increased the sensitivity of the vessel to I-epinephrine in both sexes. Male aortae in all instances had greater sensitivity to epinephrine than those of females under the same conditions. Castration markedly increased the sensitivity to epinephrine in females, especially when the castrates were placed on the salt diet, In contrast, male aortae were not particularly changed by castration.

An inhibitory effect of tolbutamide and glibenclamide (glyburide) on the pancreatic islets of normal animals

“…Pancreatic-femoral cross circulation experiments between two dogs demonstrated that, when a sulfonylurea derivative was injected into one of the animals, the second animal, recipient of the pancreatic blood of the first, becomes hypoglycemic [1,2]. This and other indirect evidence suggests that the sulfonylureas release insulin from the pancreas [3], a notion confirmed by direct measurements of insulin in vivo and in vitro [4--7] and now generally accepted.…”

Canadian and British Experiences with the Sulfonylureas

“…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.…”

The Effects of Long-term Administration of Sulfonylureas on the Carbohydrate Metabolism in Normal and Alloxanized Rats; Have Sulfonylureas a Diabetogenic Action ?

“…It is generally accepted that the most important action of these hypoglycemic agents is the stimulation of the beta cells in the Langerhans' isolets. [1][2][3][4][5][6][7][8][9][10][11][12] Recently, there have been numerous reports on secondary failure after the administration of sulfonylureas in diabetic patients.13-21) Some authors", 15,18) reported that secondary failure was due to exhaustion of the beta cells in the islets caused by the administration of sulfonylureas. If this is true, should not the carbohydrate metabolism in experimental animals deteriorate with the long term administration of sulfonylureas?…”