Clinical Use of Diazoxide and Mechanism for Its Hyperglycemic Effects

Abstract

The mechanism of diazoxide hyperglycemia in man has been studied by measurement of serum glucose, immunoreactive insulin, and plasma free fatty acids. In a patient with islet cell carcinoma, in normal subjects, and in diabetic patients, diazoxide hyperglycemia was accompanied by a decrease in serum immunoreactive insulin, an increase in plasma free fatty acids, tachycardia, and a widened pulse pressure. The similarity of these effects to those produced by epinephrine has suggested that at least some of the effects of diazoxide may be mediated by endogenous sympathetic stimulation. Diazoxide has been used successfully to control hypoglycemia in a patient with islet cell carcinoma for twenty months. DIABETES 15: 143-48, March, 1966.

Suppression of basal insulin secretion by adrenalin in normal man and in patients with insulinomas

“…Although the malignant insulinoma we studied had impaired insulin suppression by adrenalin (as did the malignant insulinoma with the same dose of adrenalin reported by Graber et al [15]), a similar response was seen in the benign insulinoma which also secreted a high proportion of proinsulin. Both tumours were therefore probably undifferentiated [16], and although an adrenalin infusion might give an indication of the degree of differentiation it is unlikely to give direct evidence of malignancy.…”

Adriamycin Therapy for Advanced Insulinoma

“…Frequently the patient suffers primarily from the effects of massive insulin secretion and dies of hypoglycemia or related complications. Attempts to inhibit insulin secretion by diazoxide administration (7) or to produce peripheral insulin resistance with glucocorticoids may be effective in controlling hypoglycemic symptoms in some patients, but are usually ineffective when hormone secretion becomes massive. L-Asparaginase may lower insulin levels in some patients by inhibiting insulin synthesis without affecting tumor mass (2,8), but due to hepatic and pancreatic toxicity of this drug its use is limited to the short term palliation of severe hypoglycemia.…”

Hyperpyruvaturia in experimental diabetes

“…The exact loci of action of diazoxide are as yet unknown, but it has been shown to reduce plasma insulin levels in vivo (Graber, Porte & Williams, 1966) and to reduce insulin release from the pancreas in vitro (Howell & Taylor, 1966).…”