Chemische Ausschaltung der A-Zellen derLangerhansschen Inseln

Holt, Claus von; Holt, L. v.; Kröner, Barbara; Kühnau, J.

doi:10.1007/bf00639249

Cited by 37 publications

(3 citation statements)

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“…These studies suggested that the hypoglycaemic property was due to a destruction of glucagon-secreting Alpha cells [16,17]. That 2254 RP affected the morphological appearance of Alpha cells was confirmed [18,19], but Gepts and collaborators [19] pointed out that the cells were degranulated, not severely damaged.…”

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confidence: 92%

The fiftieth anniversary of hypoglycaemic sulphonamides. How did the mother compound work?

Henquin

1992

Diabetologia

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Probably over 20 million patients world-wide suffering from Type 2 (non-insulin-dependent) diabetes mellitus are treated with hypoglycaemic sulphonylureas. In fact, all antidiabetic drugs currently used with the aim of stimulating insulin release belong to this family.Soon after the discovery of insulin, Abel and Geiling [1] showed that the hormone contains large amounts of sulphur which is essential for its biological action. These observations prompted several studies on the possible effects of sulphur itself on glucose homeostasis. Oral and parenteral administration of colloidal sulphur caused a small decrease in blood glucose levels in normal rabbits and humans [2-4] and slightly lowered glycaemia and glucosuria in certain diabetic patients [4,5]. The mechanisms of action of sulphur have not been clearly identified.The first report that a synthetic sulphur-containing compound may lower blood glucose probably dates from 1930 [6]. Ruiz and collaborators observed that oral or intravenous administration of 4-or 5-methyl, 2-thiolimidazole ( Fig. 1) to normal fasting rabbits was followed by a slight decrease of glycaemia, but the mechanism involved was not elucidated [6].careful study of the mechanisms underlying this hypoglycaemia [11][12][13].He demonstrated that, whatever the route of administration, 2254 RP decreased blood glucose levels in normal dogs. This hypoglycaemic effect was unaffected by vagotomy, persisted in partially pancreatectomized animals, but disappeared when the pancreatectomy was complete. The degree of hypoglycaemia was dependent on the sulphonamide concentration in plasma, but low doses were sufficient to cause a marked fall in blood glucose when they were injected directly into the pancreatic artery [11][12][13].These observations led Loubati~res to propose that the hypoglycaemic property of 2254 RP was due to its ability to stimulate insulin release through a direct action on Beta cells. Further support for this interpretation was obtained in cross-circulation experiments. When the pancreaticoduodenal vein of a normal donor dog was anastomosed to the jugular vein of a receiver dog made diabetic by alloxan, injection of the drug to the donor was followed by a decrease in blood glucose levels in the receiver [12]. The hypoglycaemic effects of 2254 RP and of a related corn-

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confidence: 92%

The fiftieth anniversary of hypoglycaemic sulphonamides. How did the mother compound work?

Henquin

1992

Diabetologia

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“…Failure of blood sugar of dog R to decrease in those experiments in which dog D did not respond to carbutamide, the slow return toward normal of blood sugar in dog R after separation from its extra insulin supply and the sustained hypoglycemia in dog D under the lasting effect of the injected drug, lend further support to the stated hypothesis. (1) studied the synthesis of plasma phospholipides in fasting hepatectomized dogs with P32 and Goldman et a L ( 2 ) repeated this study with Cl4-Iabelled palmitic acid. The available data do not permit the differentiation between the release of preformed insulin and true insulin secretion, although the fact that the B cells did not appear degranulated suggests active secretion.…”

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Insulin Secretion Following Carbutamide Injections in Normal Dogs.

Pozza

Galansino

Foà

1956

Experimental Biology and Medicine

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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.

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“…to its destructive action on the a-cells of the pancreatic islets. (For recent reviews see Ferner, 1956;von Holt et al, 1956. ) Mechanism of Action On October 7, 1955, a series of publications appeared in the Deutsche medizinische Wochenschrifit (Franke and Fuchs, 1955;Achelis and Hardebeck, 1955; Bertram…”

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Hypoglycaemic and Antidiabetic Sulphonamides

Young¹

1956

BMJ

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Chemische Ausschaltung der A-Zellen derLangerhansschen Inseln

Cited by 37 publications

References 2 publications

The fiftieth anniversary of hypoglycaemic sulphonamides. How did the mother compound work?

The fiftieth anniversary of hypoglycaemic sulphonamides. How did the mother compound work?

Insulin Secretion Following Carbutamide Injections in Normal Dogs.

Hypoglycaemic and Antidiabetic Sulphonamides

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