PURPOSE:The goal of the present study was to investigate the effects of diazoxide on 4-aminopyridine(4-AP)-induced hyperexcitability followed by normal oxygenation or an anoxia state in young rats. Also, we investigated the effects of carbamazepine(CBZP) on 4-AP-induced hyperexcitability followed by normal oxygenation or an anoxia state in young rats. METHODS:The visual cortex slices in this study were obtained from 13 to 18-days-old Sprague-Dawley rats. Extracellular recordings were performed to observe the induction of the epileptiform discharges perfused by artificial CSF containing 100 micrometer 4-AP with 7.5 mM K and the effects of 1 mM diazoxide and 50 micrometer CBZP followed by normal oxygenation or an anoxia state. RESULTS:Spontaneous epileptiform activities were observed in artificial CSF containing 100 micrometer 4-AP. The addition of diazoxide decreased the frequency of 4-AP- induced epileptiform activities followed by anoxia, but didnt block the 4-AP-induced epileptiform activities followed by anoxia. The addition of CBZP blocked the 4-AP-induced epileptiform activities followed by normal oxygenation. CONCLUSION:We observed that diazoxide did not counteract the epileptiform activities induced by 4-AP. Diazoxide inhibited the increased excitability followed an anoxia state in young rats. CBZP counteracted the epileptiform activities induced by 4-AP. Diazoxide may have limited utilities in the seizure therapy. Nevertheless, this could be of benefit during prolonged seizures where hypoxia becomes a significant factor.
Animals ; Anoxia* ; Diazoxide* ; Oxygen ; Rats* ; Rats, Sprague-Dawley ; Seizures ; Visual Cortex

We report a 45-year-old man with type 2 diabetes who presented with recurrent hypoglycemia. Biochemical and imagingstudies did not show any mass-like lesion in the pancreas, so prednisolone and diazoxide were administered for the treatment of hypoglycemia. However, the hypoglycemia persisted during and after the medical treatment. A selective arterial calcium stimulation test was performed and revealed a suspicious lesion at the head of the pancreas. The patient underwent enucleation of the pancreas head lesion. The lesion was confirmed histologically to be focal nesidioblastosis and surgical resection was successfully performed. The patient showed no hypoglycemic symptoms postoperatively.
Calcium ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Diazoxide ; Head ; Humans ; Hypoglycemia ; Middle Aged ; Nesidioblastosis ; Pancreas ; Prednisolone

Nesidioblastosis, also known as persistent hyperinsulinemic hypoglycemia of infancy(PHHI) or familial hyperinsulinsm, is the most common cause of recurrent severe hypoglycemia in infancy. It is an autosomal recessive disorder characterized by irregular insulin secretion leading to inappropriately raised plasma insulin concentration compared to blood glucose levels. Recently, mutations in the sulfonylurea receptor(SUR) have been described in association with PHHI. The mainstay of medical treatment is glucose infusion and diazoxide or long acting somatostatin. If medical treatment fails in preventing hypoglycemia, near total pancreatectomy is recommended. We report one case of nesidioblastosis cured by near total pancreatectomy with brief review of literatures.
Blood Glucose ; Congenital Hyperinsulinism* ; Diazoxide ; Glucose ; Humans ; Hypoglycemia ; Infant, Newborn* ; Insulin ; Nesidioblastosis* ; Pancreatectomy ; Plasma ; Somatostatin

PURPOSE: Currently available K+-channel openers are exclusively KATP channel openers. Among the KATP channel openers, minoxidil and diazoxide have been already used as antihypertensive agents clinically but their erectogenic activities have not been demonstrated. We performed this study to identify the effects of intracavernosal minoxidil and diazoxide on feline penile erection and also to compare that of pinacidil, relatively well-demonstrated K+-channel opener. MATERIALS AND METHODS: Using a feline model, the magnitude of penile erection caused by pinacidil was compared with that caused by minoxidil and diazoxide. With control erectile responses of intracavernosal PGE1 and papaverine, synergistic effects of erectogenic agents with KATP channel openers were also investigated in twenty-eight male cats in vivo. RESULTS: Intracavernosal injection of pinacidil increased intracavernosal pressure (ICP) in a dose-dependent fashion but minoxidil and diazoxide did not affect ICP significantly. Furthermore, pinacidil (10-5M/ml) enhanced the increase of ICP by PGE1 or papaverine but minoxidil and diazoxide did not. Noteworthy, pinacidil induced cavernous relaxation to the following erectogenic agents even in refractory cases to higher concentration (10-1M/ml) of erectogenic agent alone (n=7, p<0.01). CONCLUSIONS: These result suggests that minoxidil and diazoxide, which have been used as antihypertensive agents clinically, do not affect intracavernosal pressure. Among the KATP channel openers, pinacidil seems to be promising in producing penile erection as an alternate component of previous intracavernous injection. Also, pinacidil may be useful clinically because of the potential therapeutic effects as an intracavernosal agents in combination with PGE1 or papaverine.
Alprostadil ; Animals ; Antihypertensive Agents ; Cats ; Diazoxide* ; Humans ; Male ; Minoxidil* ; Papaverine ; Penile Erection* ; Pinacidil* ; Relaxation

OBJECTIVE: The purpose of this study was to investigate the effects of fluoxetine (Prozac) on membrane potential and ionic currents in RINm5F insulinoma cells. METHODS: Membrane potential and ionic currents in RINm5F cell were recorded by using whole-cell and perforated-patch clamp techniques. RESULTS: Under current clamp conditions, diazoxide (200 microM), an activator of K ATP channels, induced a hyperpolarization of the resting membrane potential (-16.1+/-1.4 mV, n=), which was accompanied by a abolition of action potential firing. This diazoxide-induced hyperpolarization was blocked by glibenclamide (10 microM). Fluoxetine produced significant depolarization of membrane potential (15.9+/-3.1 mV, n=) and blocked diazoxide-induced hyperpolarization. Diazoxide activated inward currents in the presence of high external K + (90 mM) at a holding potential of -60 mV. Fluoxetine suppressed diazoxide-activated currents in a concentration-dependent (IC 50 =.84 microM) manner. However, the inhibitory action of fluoxetine was not specific to K ATP currents because it also inhibited both voltage-activated K + and Ca 2+ currents in a concentration-dependent manner. K ATP currents were more sensitive to fluoxetine block than both voltage-activated K + and Ca 2+ currents. CONCLUSION: Our results indicate that fluoxetine increased excitability of RINm5F cells mainly by the preferential block of K ATP currents. Fluoxetine-induced depolarization may influence insulin secretion in insulinoma cells.
Action Potentials ; Adenosine Triphosphate ; Diazoxide ; Fires ; Fluoxetine* ; Glyburide ; Insulin ; Insulinoma* ; Membrane Potentials* ; Membranes*

Congenital hyperinsulinism (CHI), the most important cause of hyperglycemia in early infancy, is a heterogenous disease characterized by dysregulation of insulin secretion. Mutations in five proteins have been associated with CHI: sulfonyl urea receptor 1; Kir 6.2; glucokinase; glutamate dehydrogenase and mitochondrial enzyme short-chain 3-hydroxyacyl-coenzyme A dehydrogenase. Early recognition of hypoglycemia, diagnosis of CHI and appropriate management of the hypoglycemia are of the utmost importance to prevent neurologic damage. We report a case of persistent hyperinsulinemic hypoglycemia in 8-month-old male infant. This patient has no mutation in previously mentioned genes. Treatment with diazoxide was successful without any severe side effects in this patient.
Congenital Hyperinsulinism* ; Diagnosis ; Diazoxide* ; Glucokinase ; Glutamate Dehydrogenase ; Humans ; Hyperglycemia ; Hyperinsulinism ; Hypoglycemia ; Infant ; Insulin ; Male ; Oxidoreductases ; Urea

Insulin autoimmune syndrome is an uncommon cause of hypoglycemia. According to the type of antibody, it can be classified as caused by insulin or insulin receptor autoantibodies. Generally, insulin autoimmune syndrome develops following exposure to exogenous insulin or sulfhydryl medications, although insulin or insulin receptor antibody may also occur spontaneously. We treated a 54-year-old woman who developed spontaneous hypoglycemia. The patient had repeated hypoglycemia despite the infusion of dextrose solution. Her serum insulin, c-peptide, and insulin autoantibody were elevated, even during the hypoglycemic periods. Insulin receptor autoantibody and HLA-cw4/B62/DR4 were positive. After steroid and diazoxide treatment, the hypoglycemic symptoms improved gradually. No further hypoglycemic episodes occurred after tapering the medication over 1 year. We present a case of insulin autoimmune syndrome with positive insulin and insulin receptor autoantibodies.
Autoantibodies ; C-Peptide ; Diazoxide ; Female ; Glucose ; Humans ; Hypoglycemia ; Insulin ; Middle Aged ; Receptor, Insulin

PURPOSE: Persistent hyperinsulinemic hypoglycemia of infancy(PHHI), which is characterised by inappropriate insulin secretion in spite of hypoglycemia, needs urgent treatment to prevent cerebral hypoglycemic damage. Although pancreatectomy is the treatment of choice for PHHI, there are several complications which follow treatment. We suggest that aggressive medical therapy, when effective, is preferable to partial pancreatectomy. METHODS: We evaluated 8 patients with PHHI admitted to the Department of Pediatrics, Samsung Medical Center from November 1996 to January 1999. Children with hypoglycemia in the range of 3-50mg/dl were included. Octreotide was administered at dosage of 100-150 microgram/day. When the patients did not respond to octreotide, diazoxide and nifedipine were given in addition. RESULTS: In four of eight patients, octreotide was discontinued after 15 to 165 days. One patient was given diazoxide instead. The remaining 3 patients are still being treated with octreotide. CONCLUSION: We believe that maximum effort should be made to attain euglycemia with medication, and pancreatectomy should be reserved for patients in whom these measures fail to restore normoglycemia.
Child* ; Congenital Hyperinsulinism* ; Diazoxide ; Humans ; Hypoglycemia ; Insulin ; Nifedipine ; Octreotide ; Pancreatectomy ; Pediatrics

Congenital hyperinsulinism is the most frequent cause of severe, persistent hypoglycemia in infancy and childhood. It is caused by an inappropriate insulin secretion from the pancreatic beta-cells secondary to various genetic disorders. Recognition of this entity becomes important due to the fact that hypoglycemia is very severe and frequent and that it may lead to severe neurological damage in the infant manifesting as mental or psychomotor retardation or even a life-threatening events if not recognized and treated effectively in time. Hypoglycemias can be detected by seizures, fainting, or any other neurological symptoms in the neonatal period or later, usually within the first two years of life. Hypoglycemias must be rapidly and intensively treated to prevent severe and irreversible brain damages. Next, a treatment to prevent the recurrence of hypoglycemia must be set, which may include frequent and glucose-enriched feeding, diazoxide and octreotide. We report a case of congenital hyperinsulinemia in a 2 months old infant presenting as atonic seizure which has been treated with diazoxide.
Brain ; Congenital Hyperinsulinism* ; Diazoxide ; Humans ; Hyperinsulinism ; Hypoglycemia ; Infant* ; Insulin ; Octreotide ; Recurrence ; Seizures* ; Syncope

A 2.4 kg baby boy born via Caesarian section at 35 weeks had the first onset of hypoglycemia at 2 hours of life. The infant required a glucose load of 30 mg/kg/min. Insulin level was 19.6 pmol/L (normal value 17.8-173.0) in the absence of ketosis. He was resistant to oral diazoxide but responded to octreotide infusion. The boy was found to be heterozygous for an ABCC8 nonsense mutation, p.R934*. We present our experience on the use of subcutaneous octreotide for 2 years for the treatment of diazoxide resistant congenital hyperinsulinism (CHI).

Male ; Infant ; Codon, Nonsense ; Congenital Hyperinsulinism ; Diazoxide ; Glucose ; Infant ; Insulins ; Ketosis ; Octreotide ; Parturition ; Pregnancy ; Mutation