Diazoxide has been identified as a mitochondrial, ATP-dependent K(+) channel opener, and a potentially neuroprotective compound under ischemic conditions. We set out to characterize the consequences of various treatment strategies with diazoxide in a rat model of chronic cerebral hypoperfusion. Cerebral hypoperfusion was induced by permanent, bilateral occlusion of the common carotid arteries (...

Ischemia reperfusion injury (IR injury) is a common problem in clinical conditions. Researches have frequently revealed that ATP- sensitive potassium (KATP) channels and nitric oxide plays a role in protection against ischemic injury in skeletal muscle. The present study aimed at evaluating the possible link between this two pathways. Sixty-eight male wistar rats, were pretreated with saline, d...

BACKGROUND Mutations in ABCC8 and KCNJ11 are the most common cause of congenital hyperinsulinism (CHI). Recessive as well as dominant acting ABCC8/KCNJ11 mutations have been described. Diazoxide, which is the first line medication for CHI, is usually ineffective in recessive ABCC8 mutations. We describe the clinical and molecular characterisation of a recessive ABCC8 mutation in a CHI patient t...

OBJECTIVES To examine the effect of diazoxide on hypoxia-induced soluble fms-like tyrosin kinase-1 (sFlt-1) release in JEG-3 choriocarcinoma cells. METHODS Cells were cultured under normoxia (20% O2) or hypoxia (1% O2), and expression of sFlt-1 mRNA and protein release was determined by quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR) assays and enzyme-linked i...

The disposition and systemic vascular effects of bolus intravenous doses of diazoxide (3.75,7.5, and 15.0 mg/kg) were studied in anesthetized open-chest dogs. Blood flow (0) and right atrial pressure (Pra) were independently controlled by a right heart bypass. The late phase disposition halflife (beta t Vt) of diazoxide averaged 3.4 ± 0.5 hrs (x ± SEM) with an apparent volume of distribution at...

background: diazoxide is the main therapeutic agent for congenital hyperinsulinism. the drug is generally well tolerated; however, in this report severe adverse effects including heart failure (hf) and pulmonary hypertension (ph) in an infant are reported.case report: a sixteen-day male infant with persistent hypoglycemia and with diagnosis of congenital hyperinsulinism underwent near total pan...

Similar to ischemic preconditioning, diazoxide was documented to elicit beneficial bioenergetic consequences linked to cardioprotection. Inhibition of ATPase activity of mitochondrial F(0)F(1) ATP synthase may have a role in such effect and may involve the natural inhibitor protein IF(1). We recently documented, using purified enzyme and isolated mitochondrial membranes from beef heart, that di...

Ethanol-induced acute gastric ulceration (EIGU) is widely studied. ATP dependent potassium channel (KATP) modulators are thought to interfere with some physiologic functions of the stomach. We have studied the effects of different doses of KATP modulators (diazoxide as agonist and glibenclamide as antagonist) on EIGU in rats. Gastric lesions were quantified. Fasting blood glucose (FBS) levels w...

The mitochondrial ATP-sensitive K(+) (mitoKATP) channel plays a significant role in mitochondrial physiology and protects against ischemic reperfusion injury in mammals. Although fish frequently face oxygen fluctuations in their environment, the role of the mitoKATP channel in regulating the responses to oxygen stress is rarely investigated in this class of animals. To elucidate whether and how...

BACKGROUND Ischemic preconditioning accelerates suppression of gap junction (GJ) permeability during myocardial ischemia, and GJ blockers reduce infarct size. We hypothesized that the mitochondrial ATP-sensitive K+ (mitoKATP) channel is one of the mechanisms regulating GJ permeability through the mitogen-activated protein kinase ERK, leading to cardioprotection. METHODS AND RESULTS In isolate...