The effect of placebo or methysergide (2 mg. every six hours) on the plasma glucose and insulin response to 1 gm. of intravenous tolbutamide was studied in eighteen patients with adult onset diabetes mellitus. Neither placebo nor methysergide caused any alteration in the hypoglycemic action of tolbutamide as compared to control tolbutamide studies. Tolbutamide-stimulated insulin secretion after two days of placebo administration was not significantly different from results in the control tolbutamide studies (−6.1 ± 9.8 per cent, mean ± S.E.). Methysergide pretreatment resulted in a significant potentiation of tolbutamide-mediated insulin secretion (39.3 ± 6.1 per cent) as compared to responses in the control tolbutamide studies. The present data indicate that methysergide potentiates tolbutamide – as well as glucose-mediated insulin secretion in patients with adult onset diabetes mellitus.

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