Individuals with long-standing type 1 diabetes (T1D) are at increased risk of severe hypoglycemia secondary to impairments in normal glucose counterregulatory responses (CRR). Strategies to prevent hypoglycemia are often ineffective highlighting the need for novel therapies. ATP-sensitive potassium (KATP) channels within the hypothalamus are thought to be integral to hypoglycemia detection and ...

Intracellular calcium signaling plays a central role in cell proliferation. In leukemic cells, the calcium release-activated calcium channels provide a major pathway for calcium entry (I(CRAC)) perpetuating progression through the cell cycle. Although I(CRAC) is under mitochondrial regulation, targeting mitochondrial function has not been exploited to control malignant cell growth. The benzothi...

Injection of rats either with diazoxide (25 mg/kg iv), isoproterenol (0.33 mg/kg sc), or hydralazine (HDZ) (10 mg/kg ip) decreased arterial blood pressure from approximately 120 to 70-80 mmHg and stimulated renin secretion. However, diazoxide and isoproterenol treatments each stimulated water ingestion, whereas HDZ treatment did not. HDZ treatment did not reduce water intake evoked by systemic ...

Extracellular signal regulated kinases (ERKs) are key regulatory proteins that mediate cell survival, proliferation and differentiation. Reactive oxygen species (ROS) may play a role in activation of the ERK pathway. Since mitochondria are a major source of ROS, we investigated whether mitochondrial-derived ROS play a role in ERK activation. Diazoxide, a potent mitochondrial ATP-sensitive K + c...

The ATP-sensitive K(+) (K(ATP)) channels are composed of the pore-forming K(+) channel Kir6.0 and different sulfonylurea receptors (SURs). SUR1, SUR2A, and SUR2B are sulfonylurea receptors that are characteristic for pancreatic, cardiac, and vascular smooth muscle-type K(ATP) channels, respectively. The structural elements of SURs that are responsible for their different characteristics have no...

ketotifen is a benzocycloheptathiophene with a range of pharmacological activities. the present study was carried out to evaluate the action of ketotifen on isolated rat bladder contractions induced by kci and acetylcholine, compared with the effects of other drugs. ketotifen (5 µm) reduced the response to acetylcholine on rat isolated bladder without altering the maximum response and shifted t...

There are no studies in vivo on the effects of insulin on androgens and sex hormone-binding globulin (SHBG) in men. We, therefore, investigated the effects of insulin suppression on testosterone and SHBG in two groups of eight nondiabetic adult obese men and six healthy normal weight men who underwent diazoxide treatment (100 mg, three times daily) for 7 days. Blood samples for hormone determin...

BACKGROUND Congenital hyperinsulinism (CHI) is a clinically heterogeneous condition. Mutations in eight genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A and HNF1A) are known to cause CHI. AIM To characterise the clinical and molecular aspects of a large cohort of patients with CHI. METHODOLOGY Three hundred patients were recruited and clinical information was collected before genotypi...

Mitochondria affect cerebrovascular tone by activation of mitochondrial ATP-sensitive K+ (K ATP) channels and generation of reactive oxygen species (ROS). Insulin resistance accompanying obesity causes mitochondrial dysfunction, but the consequences on the cerebral circulation have not been fully identified. We evaluated the mitochondrial effects of diazoxide, a putative mitochondrial K ATP cha...