Studies on the mechanism of disopyramide-induced hypoglycemia.

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The effects of disopyramide on blood glucose and plasma immunoreactive insulin (IRI) were studied in Donryu and Long-Evans strain rats. The configurations of the blood glucose curves after oral administration of disopyramide could be grouped into two types, initial and sustained hypoglycemia. Initial hypoglycemia, which seemed insulin independent, was observable in all of the tested rats, while sustained response, in which the hypoglycemia was accompanied by a rise in plasma IRI, could be found only in a few of thetested animals. The incidence for the sustained response was four out of nineteen. Afterpretreatment with propranolol, this rate rose to thirteen out of sixteen, while pretreatmentwith phentolamine or hexamethonium did not have any significant effect. In the isolatedpancreas in situ perfusion experiment, the incidence of cases showing stimulated insulinrelease induced by perfusion of disopyramide was two out of six, and pretreatment withpropranolol produced a significant rise of the rate to five out of six. In the isolated pancreatic islet perifusion experiment, disopyramide always produced an increase in insulinrelease from the islets, but the addition of propranolol did not lead to any change in thedisopyramide-induced insulin hypersecretion. Disopyramide was concluded to producetwo distinct effects: one was the direct stimulation of insulin release from B cells, and theother was elevation of the activity of the β-adrenergic neuron, which plays a physiological role in suppressing insulin secretion.
一般社団法人日本臨床薬理学会の論文

Studies on the mechanism of disopyramide-induced hypoglycemia.

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