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Hemmung der Insulininkretion durch α-Receptoren stimulierende Substanzen

Inhibition of insulin secretion by alpha adrenergic stimulatory agents

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Summary

Experiments are described in which the influence of an α-adrenergic blocking agent, phentolamine, and of two hypotensive drugs, diazoxide and 2-(2,6-dichlorophenylamino)-2-imidazoline hydrochloride (DCAI) on blood glucose, plasma insulin and glucose-stimulated insulin secretion has been measured in male Wistar rats.

Blood glucose concentration has been found to be decreased and plasma insulin concentration has been found to be increased after one or two injections of 50 mg phentolamine/kg b.w., intraperitoneally. These results are in accordance with the observation that α-adrenergic stimulation inhibits and β-adrenergic stimulation promotes insulin secretion (Porte, 1967 a, 1967 b). If the α-adrenergic stimulatory effect of endogenous catecholamines is blocked by phentolamine, the remaining β-adrenergic stimulatory effect of endogenous epinephrine leads to an increase in insulin secretion.

Treating rats with diazoxide (200 mg/kg b.w., i.v.) or DCAI (200 μg/kg b.w., s.c.), respectively, has been found to lead to a decrease in plasma insulin concentration as well as to an almost complete inhibition of the ability of the pancreas to secrete insulin in response to an elevation of blood glucose concentration. As these effects have been found to be abolished by pretreatment with phentolamine, the inhibition of insulin secretion caused by diazoxide and DCAI may be regarded as being mediated by α-adrenergic stimulation.

Recent studies of Turtle and Kipnis (1967) have shown that α-adrenergic stimulation lowers islet 3′,5′-AMP concentration and prevents the increase in islet 3′,5′-AMP concentration which is caused by β-adrenergic stimulation. In view of these results indicating an antagonistic influence of α- and β-adrenergic stimulation on 3′,5′-AMP formation in islet tissue, the inhibitory action of diazoxide and DCAI on insulin secretion may be explained by a decrease in adenyl cyclase activity in this tissue.

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Authors and Affiliations

  1. Pharmakologisches Institut der Freien Universität Berlin, Germany

    G. Senft, R. Sitt, W. Losert, G. Schultz & M. Hoffmann

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  1. G. Senft
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  2. R. Sitt
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  3. W. Losert
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  4. G. Schultz
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  5. M. Hoffmann
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Am 31. Oktober 1967 verstorben.

Wir danken der Deutschen Forschungsgemeinschaft für die Unterstützung unserer Untersuchungen.

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Senft, G., Sitt, R., Losert, W. et al. Hemmung der Insulininkretion durch α-Receptoren stimulierende Substanzen. Naunyn-Schmiedebergs Arch. Pharmak. u. Exp. Path. 260, 309–323 (1968). https://doi.org/10.1007/BF00537636

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