Enhancement of Insulin Secretion in Adult Onset Diabetics by Methysergide Maleate: Evidence for an Endogenous Biogenic Monoamine Mechanism as a Factor in the Impaired Insulin Secretion in Diabetes Mellitus

Reversal by methysergide of inhibition of insulin secretion by prostaglandin E in the dog.

“…Our observation that methysergide can reverse inhibition of insulin secretion by PGE gives rise to new considerations regarding the data of Quickel et al (10) which provided the interesting demonstration that methysergide augments insulin secretion in diabetic humans. These studies were interpreted as evidence for the existence of an endogenous pancreatic biogenic monoamine mechanism that inhibits insulin release in adult-onset diabetic patients.…”

“…There has been no published work assessing potential interactions between serotonin and PGE during regulation of insulin secretion in vivo, but it seems reasonable to hypothesize that such interactions exist. This contention arises from the facts that both serotonin and PGE are produced in the islet, both inhibit in vivo insulin secretion, both have effects that are similar in other tissues (e.g., intestinal smooth muscle), and both have been postulated to play a role in the abnormal insulin secretion characteristic of diabetes mellitus (10,11).…”

Potentiation of Tolbutamide-mediated Insulin Release in Adult Onset Diabetics by Methysergide Maleate

“…1 " 3 Investigations in human beings have shown that administration of methysergide maleate, a purported serotonin antagonist, potentiates glucose-stimulated insulin secretion in patients with adult onset diabetes mellitus, but not in normal volunteers. 4 These data suggested that impairment of insulin secretion with maturity onset diabetes mellitus might be due to a specific abnormality in endogenous pancreatic beta cell monoamines.…”

“…In the dose used, methysergide does not alter the secretion of adrenal corticosteroids, catecholamines, or serotonin as estimated by the twenty hour urinary excretion of metabolites. 4 Methysergide has no effect on plasma growth hormone levels. 4 Preliminary studies from our laboratory indicate that methysergide does not alter the ti/2 disappearance of plasma insulin or the biologic action of exogenously administered insulin (unpublished observations: C.H.…”

“…4 Methysergide has no effect on plasma growth hormone levels. 4 Preliminary studies from our laboratory indicate that methysergide does not alter the ti/2 disappearance of plasma insulin or the biologic action of exogenously administered insulin (unpublished observations: C.H. Bivens, J.M.…”