by Activation of Sarcolemmal but not Mitochondrial ATP-Sensitive Potassium Channels in Mice To the Editor: Recently, Suzuki et al1 reported that attenuation of myocardial stunning by diazoxide in mice was mediated through activation of sarcolemmal rather than mitochondrial K ATP channels. Although the authors used an elegant approach by combining both pharmacological tools (utilizing the mitoch...

We investigated effects of diazoxide, a selective opener of mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channels, against brain damage after middle cerebral artery occlusion (MCAO) in male Wistar rats. Diazoxide (0.4 or 2 mM in 30 microl saline) or saline (sham) was infused into the right lateral ventricle 15 min before MCAO. Neurological score was improved 24 h later in the animals treated w...

OBJECTIVE The phenotype associated with heterozygous HNF4A gene mutations has recently been extended to include diazoxide responsive neonatal hypoglycemia in addition to maturity-onset diabetes of the young (MODY). To date, mutation screening has been limited to patients with a family history consistent with MODY. In this study, we investigated the prevalence of HNF4A mutations in a large cohor...

OBJECTIVE The role of mitochondria and in particular of mitochondrial uncoupling in the mechanism of cardioprotection is not defined. In the accompanying paper we have shown that pretreatment of isolated rat hearts with a low concentration (100 nM) of FCCP, prior to global ischaemia, is cardioprotective, while 300 nM FCCP exacerbates injury. Here we define the mitochondrial responses to increas...

We studied the in vivo and in vitro effects of diazoxide on the cerebral circulation of 8 normotensive (mean arterial pressure = 100 mm Hg) and 5 renal hypertensive (mean arterial pressure = 146 mm Hg) goats. Injections of diazoxide (0.3-27 mg) into the internal maxillary artery of unanesthetized goats produced dose-dependent increases in cerebral blood flow (electromagnetic flowmeter), this ef...

Insulin resistance (IR) precedes the onset of Type 2 diabetes, but its impact on preconditioning against myocardial ischemia-reperfusion injury is unexplored. We examined the effects of diazoxide and ischemic preconditioning (IPC; 5-min ischemia and 5-min reperfusion) on ischemia (30 min)-reperfusion (240 min) injury in young IR Zucker obese (ZO) and lean (ZL) rats. ZO hearts developed larger i...

Objective. We investigated whether and how diazoxide can attenuate brain injury after cardiopulmonary resuscitation (CPR) by selective opening of mitochondrial ATP-sensitive potassium (mitoKATP) channels. Methods. Adult male Sprague-Dawley rats with induced cerebral ischemia (n = 10 per group) received an intraperitoneal injection of 0.1% dimethyl sulfoxide (1 mL; vehicle group), diazoxide (10 ...

BACKGROUND Several clinical conditions are associated with white matter injury, including periventricular white matter injury (PWMI), which is a form of brain injury sustained by preterm infants. It has been suggested that white matter injury in this condition is due to altered oligodendrocyte (OL) development or death, resulting in OL loss and hypomyelination. At present drugs are not availabl...

Ferroni et al. described pretreatment insulin levels as a prognostic factor for breast cancer and suggested interventions targeting glucose metabolism with metformin to improve survival of these patients [1]. We recently reviewed this topic [2] and agree with this approach, but we believe that diazoxide should also be mentioned in this context. Diazoxide is a nondiuretic benzothiadiazine that p...