Neutral Red Induced Hyperglucagonemia1

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Abstract
Previous reports of hyperglycemia, reduction in hepatic glycogen and degranulation of alpha cells in the islets of Langerhans in rats following neutral red administration, has suggested that this dye stimulates glucagon release and/or promotes alpha cell destruction. In the present investigation similar studies in dogs, utilizing radio-immunoassay methods, have revealed peripheral venous hyperglucagonemia in association with neutral red induced hyperglycemia. Serum insulin response was noticeably blunted in the face of elevated blood sugar levels following intravenous neutral red. In rabbits, the intravenous administration of neutral red resulted in a 50% reduction in extractable pancreatic radioimmunoassayable glucagon. Hyperglucagonemia provoked by neutral red is secondary to abrupt release of preformed glucagon with ensuing hepatic glycogenolysis. The answer to the question of whether this dye actually promotes irreversible alpha cell destruction and a state of acquired glucagon deficiency must await hormonal analysis data from the chronically prepared animal.