Disease relevance of diazoxide

• A mutation in the second nucleotide-binding fold (NBF2) of the sulfonylurea receptor (SUR) of an individual diagnosed with persistent hyperinsulinemic hypoglycemia of infancy generated KATP channels that could be opened by diazoxide but not in response to metabolic inhibition [1].
• Neonatal hyperglycemia following maternal diazoxide administration [2].
• Hypotension and bradycardia following diazoxide and hydralazine therapy [3].
• The patient's hyperinsulinism was easily controlled with diazoxide and chlorothiazide [4].
• Acute stimulation of renin release by isoprenaline, tilting, or diazoxide in 13 normotensive individuals and in 9 patients with essential hypertension increased active plasma-renin and reduced inactive plasma-renin [5].

Psychiatry related information on diazoxide

• Diazoxide in the management of severe hypertension after electroconvulsive therapy [6].
• In order to clarify the role of endogenous insulin in generating normal and pathological feeding behaviors, the effect of an anti-insulin drug, Diazoxide, on the meal pattern has been investigated in both normal and VMH rats [7].
• Gender differences in effects of pinacidil but not diazoxide on heart automatism in the isolated guinea pig right atria [8].
• Diazoxide had no significant effect on the basal fetal heart rate (FHR) or on the latency period or amplitude of late decelerations in the 3 patients with abnormal (positive) stress cardiotocographs (SCTG) and abnormal (unreactive) non-stress cardiotocographs (NSCTG) [9].
• Most cases are associated with malignant tumors or non-malignant condition such as porphyria cutanea tarda, AIDS, anorexia nervosa, thyrotoxicosis, or secondary to topical or systemic drugs (e.g. cyclosporine, phenytoin, diazoxide, minoxidil) [10].

High impact information on diazoxide

• Diazoxide in primary pulmonary hypertension [11].
• We show here that the primary site at which ATP acts to mediate K-ATP channel inhibition is located on Kir6.2, and that SUR1 is required for sensitivity to sulphonylureas and diazoxide and for activation by Mg-ADP [12].
• Chemical preconditioning with diazoxide, a mitochondrial ATP-sensitive potassium channel agonist, prevented dendritic beading and restored long-term potentiation [13].
• Therapy for persistent hyperinsulinemic hypoglycemia of infancy. Understanding the responsiveness of beta cells to diazoxide and somatostatin [14].
• First, like muscle contraction, pharmacologic activation of KATP channels with diazoxide in resting hindlimb dose dependently attenuated the vasoconstrictor responses to either sympathetic nerve stimulation or intraarterial UK 14,304 [15].

Chemical compound and disease context of diazoxide

• During the next 9 years, his liver metastases continued to grow and his fasting serum glucose level was maintained at 35 to 116 mg/dL with diazoxide and hydrochlorothiazide therapy [16].
• Baseline glucagon levels, the glucagon response to intravenous arginine, and the autonomic (adrenomedullary, sympathetic neural, and parasympathetic neural) responses to hypoglycemia were not altered by diazoxide [17].
• Previous studies had shown that administration of streptozotocin to rats produces both diabetes and hemolysis and that both could be ameliorated by prior injections of diazoxide [18].
• Chlorpropamide-induced hypoglycemia: successful treatment with diazoxide [19].
• Two other compounds that induce hirsutism, diphenylhydantoin and diazoxide, did not displace [3H]DHT [20].

Biological context of diazoxide

• Changes in oxygen consumption were sensitive to adenosine triphosphate (ATP), diazoxide, and 5-hydroxydecanoate, indicating they are attributable to mitochondrial ATP-sensitive K(+) channel (mitoK(ATP)) activity [21].
• In 14 patients with hypertensive crisis treated with diazoxide, close monitoring of blood pressure, heart rate, and symptoms was performed [22].
• In a cellular model of simulated ischemia, inclusion of diazoxide decreased the rate of cell death to about half of that in controls [23].
• Cell death by apoptosis was also significantly decreased in diazoxide pretreated hearts (3.2%) as compared with I/R (11.3%) [24].
• No mitochondrial depolarization could be detected when the membrane potential was measured by using very low light photomultiplier and confocal fluorescence imaging under the K(ATP) channel opener diazoxide [25].

Anatomical context of diazoxide

• The SUR2/Kir6.2 channel is less sensitive than the SUR/Kir6.2 channel (the pancreatic beta cell KATP channel) to both ATP and the sulfonylurea glibenclamide and is activated by the cardiac K(ATP) channel openers, cromakalim and pinacidil, but not by diazoxide [26].
• Protection of cardiac mitochondria by diazoxide and protein kinase C: implications for ischemic preconditioning [27].
• 2. The potassium channel opener diazoxide has hyperglycemic and hypotensive properties that stem from its ability to open K(ATP) channels in pancreas and smooth muscle [28].
• Diazoxide opens ATP-sensitive K+ channels in adenohypophysis cells as it does in pancreatic beta cells and also induces a hyperpolarization (approximately 30 mV) that is also suppressed by antidiabetic sulfonylureas [29].
• This reflex vasodilator-induced cardio-acceleration after propranolol adminstration could be the result of incomplete blockade of endogenously released neurotransmitter, inhibition of the parasympathetic nervous system, or a direct pharmacologic action of diazoxide [30].

Associations of diazoxide with other chemical compounds

• Both glibenclamide and sodium 5-hydroxydecanoic acid inhibited K+ flux through the diazoxide-opened mitochondrial KATP [31].
• Application of the K(ATP) channel opener diazoxide or the ob gene product leptin mimicked the effect of glucose removal in a reversible manner; moreover, hyperpolarizations evoked by either agent were inhibited by tolbutamide [32].
• Patch-clamping of matched chimeric human SUR1-SUR2A/K(IR)6.2 channels was used to identify the SUR regions that specify the selective response of sarcolemmal versus beta-cell channels to cromakalim or pinacidil versus diazoxide [33].
• Furthermore, we have shown previously that 5-hydroxydecanoate is partially metabolized, and we hypothesized that fatty acid metabolism may explain the ability of this putative mitochondrial K(ATP) channel blocker to inhibit diazoxide-induced flavoprotein fluorescence, commonly used as an assay of K(ATP) channel activity [34].
• Sustained depolarization (by tolbutamide, arginine, or high K+) and hyperpolarization (by diazoxide) of B-cells caused sustained increases and decreases of Ca2+i, respectively [35].

Gene context of diazoxide

• SUR1- and SUR2-based channels are distinguished by their differential sensitivity to sulfonylureas, whereas SUR2A-based channels are distinguished from SUR2B channels by their differential sensitivity to diazoxide [36].
• Constitutive activation of ATP-sensitive potassium channels by diazoxide does not alter leptin inhibition of preproinsulin mRNA levels [37].
• Importantly, both mutant channels rescued to the cell surface have normal ATP, MgADP, and diazoxide sensitivities, demonstrating that SUR1 harboring either the A116P or the V187D mutation is capable of associating with Kir6.2 to form functional K(ATP) channels [38].
• Diazoxide that attenuates voltage-activated Ca(2+) currents inhibited MIN6N8 cell death by IFN-gamma/TNF-alpha, while glibenclamide that accentuates voltage-activated Ca(2+) currents augmented insulinoma cell death [39].
• Diazoxide increased the levels of Bcl2 and inhibited the association of Bax with mitochondria in neurons exposed to an apoptotic insult, suggesting that activation of mitochondrial ATP-sensitive potassium channels may stabilize mitochondrial function by differentially modulating proapoptotic and antiapoptotic proteins [40].

Analytical, diagnostic and therapeutic context of diazoxide

• 16 infants with sporadic PHHI resistant to diazoxide and who underwent pancreatectomy were investigated [41].
• The present study used a model of prolonged cold heart storage to assess whether the mitochondrial K(ATP) opener diazoxide could reproduce the protection conferred by ischemic preconditioning [42].
• In conclusion, activation of mitoK(ATP) channel with diazoxide produces late PC against reperfusion injury [24].
• Both diazoxide and NNC 55-0118 dose-dependently increased total pancreatic and islet blood flow in the presence of moderate hyperglycemia, but had no effects on the blood perfusion of other splanchnic organs [43].
• Coculture with 0.3 mmol/l diazoxide was performed to probe the role of overstimulation [44].

References