We have previously shown that connexin 43 (Cx43) is present in mitochondria, that its genetic depletion abolishes the protection of ischemia- and diazoxide-induced preconditioning, and that it is involved in reactive oxygen species (ROS) formation in response to diazoxide. Here we investigated the intramitochondrial localization of Cx43, the mechanism of Cx43 translocation to mitochondria and t...

PURPOSE To examine the mechanisms of ischemic preconditioning (IPC) related to the opening of mitochondrial KATP (mKATP) channels in the retina. METHODS Rats were subjected to retinal ischemia after IPC, or retinas were rendered ischemic after pharmacological opening of mKATP channels. The effects of blocking mKATP channel opening, nitric oxide synthase (NOS) subtypes, or protein kinase C (PK...

Congenital hyperinsulinism (CHI) is the commonest cause of persistent hypoglycemia in neonates. Diazoxide is the first-line drug in its treatment, but the more severe cases are usually diazoxide-resistant. Recessive ABCC8 and KCNJ11 mutations are responsible for most (82%) of the severe diazoxide-unresponsive CHI. Oral nifedipine has been effective in isolated cases of CHI. Successful treatment...

Congenital or monogenic hyperinsulinism (HI) is a group of rare genetic disorders characterized by dysregulated insulin secretion and the most common cause persistent hypoglycemia in children. Knowledge normal glucose homeostasis allows for better understanding underlying pathophysiology hyperinsulinemic hypoglycemia, facilitating timely diagnosis management. The goal management to prevent cere...

OBJECTIVE To determine whether the common side effect of ankle oedema with arteriolar vasodilators such as the calcium entry blocker (CEB) nifedipine and the potassium channel opener (PCO) diazoxide is the direct result of peripheral vasodilation or merely a consequence of renal sodium retention. DESIGN In 12 healthy sitting volunteers we studied for 3 h the effects of 20 mg nifedipine, 150 m...

Activation of mitochondrial K(ATP) (mitoK(ATP)) channel induces acute ischemic preconditioning (PC) against ischemic injury. The ability of this channel to elicit late PC remains unknown. The present study tests the hypothesis that stimulation of mitoK(ATP) channel induces late PC via the protein kinase C (PKC) signaling pathway. Rats were subjected to 30 minutes of regional ischemia and 120 mi...

OBJECTIVE Beta cells of pancreatic islets are susceptible to functional deficits and damage by hypoxia. Here we aimed to characterize such effects and to test for and pharmacological means to alleviate a negative impact of hypoxia. METHODS AND DESIGN Rat and human pancreatic islets were subjected to 5.5 h of hypoxia after which functional and viability parameters were measured subsequent to t...

Neurons express a variety of plasma-membrane potassium channels that play important roles in regulating neuronal excitability and synaptic transmission, but also contain mitochondrial ATP-sensitive potassium channels, the functions of which are unknown. Studies of cardiac cells suggest that similar mitochondrial ATP-sensitive potassium channels are involved in the process of ischemic preconditi...