FRIDAY, Nov. 11 (HealthDay News) -- Oral administration of diazoxide, a hypothalamic ATP-sensitive potassium (KATP) channel activator, decreases endogenous glucose production (EGP) in humans without diabetes and in rats, according to an experimental study published online Nov. 7 in the Journal of Clinical Investigation.
Preeti Kishore, M.B.B.S., from the Albert Einstein College of Medicine in New York City, and colleagues presented evidence of central nervous system pathways regulating EGP in humans that is consistent with complementary rodent studies. A total of 10 individuals without diabetes were randomized to receive oral diazoxide or matched placebo in four-hour euglycemic pancreatic clamp studies. Twenty-two 5- to 7-week-old male Sprague Dawley rats were orally administered saline control, diazoxide, diazoxide with an intracerebroventricular (ICV) infusion of KATP channel blocker glibenclamide, or saline with ICV glibenclamide. Blood tests were performed to measure the human plasma glucose, insulin, C-peptide, free fatty acid, and glucagon levels. Western blot analysis and polymerase chain reaction were performed to examine the rat liver tissue.
The investigators found that EGP decreased substantially in both humans and rats after oral administration of diazoxide under fixed hormonal conditions. An appreciable concentration of diazoxide was attained in the cerebrospinal fluid of rats after administration of comparable doses of oral diazoxide, and ICV administration of glibenclamide inhibited the effects of oral diazoxide.
"These results suggest that activation of hypothalamic KATP channels may be an important regulator of EGP in humans and that this pathway could be a target for treatment of hyperglycemia in type 2 diabetes mellitus," the authors write.