cytochrome-c-t and Metabolic-Diseases

Mitochondria are sources of energy production through their role in producing adenosine triphosphate for cell metabolism. Defective mitochondrial biogenesis and function play relevant roles in the pathophysiology of relevant diseases, including obesity, diabetes mellitus, myopathies, and neurodegenerative diseases. Their function is the product of synthesis of macromolecules within the mitochondria and import of proteins and lipids synthesized outside the organelles. Both are required for mitochondrial proliferation and may also facilitate the growth of preexisting mitochondria. Recent evidence indicates that these events are regulated in a complex way by several agonists and environmental conditions, through activation of specific signaling pathways and transcription factors. Nitric oxide (NO) appears to be a novel modulator of mitochondrial biogenesis. High levels of NO acutely inhibit cell respiration by binding to cytochrome c oxidase. Conversely, chronic, low-grade increases of NO stimulate mitochondrial biogenesis in diverse cell types. Here, we suggest that some types of nutrients, including specific mixtures of amino acids, may improve mitochondrial biogenesis and energy production in energy-defective conditions by increasing endothelial NO synthase expression.

Topics: Amino Acids; Caloric Restriction; Cytochromes c; Dietary Supplements; Energy Metabolism; Humans; Metabolic Diseases; Mitochondria; Mitochondria, Heart; Nitric Oxide

A-type dimeric epigallocatechin-3-gallate (A-type-EGCG-dimer, AEd), a new proanthocyanidins dimer from persimmon fruits, has been shown to have health benefit effects. However, A-type-EGCG-dimer affects gluose metabolism in the liver and the underlying mechanism is not clarified. The present study aims to examine the protective effects of A-type-EGCG-dimer on Pb-induced hepatic insulin resistance, endoplasmic reticulum (ER) stress and apoptosis in rats. Male wistar rats exposed to 0.05% w/v Pb acetate in the drinking water with or without A-type-EGCG-dimer coadministration (200 mg/kg body weight/day, intragastrically) for three months. We found that A-type-EGCG-dimer and pioglitazone supplementation significantly deceased glucose and insulin levels in plasma as compared with the Pb group. A-type-EGCG-dimer markedly prevents Pb-induced oxidative stress, ER stress and apoptosis in livers. A-type-EGCG-dimer and pioglitazone reduced the expression levels of the GRP78, PEPCK, G6Pase, p-PERK, p-IRE1, p-JNK, ATF4, CHOP and increased p-AKT in livers of the Pb group. Moreover, A-type-EGCG-dimer reduced ROS production and restored the activities of SOD and GPx in livers. A-type-EGCG-dimer decreased Bax, cytosolic cytochrome c and cleaved caspase-3 and increased Bcl-2 in livers of Pb-exposed rats. Our results suggest that A-type-EGCG-dimer might be a potential natural candidate for the prevention of hepatic insulin resistance and apoptosis induced by Pb.

Topics: Animals; Apoptosis; Blood Glucose; Catechin; Cytochromes c; Dimerization; Diospyros; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Humans; Insulin; Insulin Resistance; Lead; Liver; Male; Metabolic Diseases; Oxidative Stress; Plant Extracts; Rats; Signal Transduction

The aim of the study was to assess the relative control of insulin secretion rate (ISR) by calcium influx and signaling from cytochrome c in islets where, as in diabetes, the metabolic pathways are impaired. This was achieved either by culturing isolated islets at low (3 mm) glucose or by fasting rats prior to the isolation of the islets. Culture in low glucose greatly reduced the glucose response of cytochrome c reduction and translocation and ISR, but did not affect the response to the mitochondrial fuel α-ketoisocaproate. Unexpectedly, glucose-stimulated calcium influx was only slightly reduced in low glucose-cultured islets and was not responsible for the impairment in glucose-stimulated ISR. A glucokinase activator acutely restored cytochrome c reduction and translocation and ISR, independent of effects on calcium influx. Islets from fasted rats had reduced ISR and cytochrome c reduction in response to both glucose and α-ketoisocaproate despite normal responses of calcium. Our data are consistent with the scenario where cytochrome c reduction and translocation are essential signals in the stimulation of ISR, the loss of which can result in impaired ISR even when calcium response is normal.

Topics: Animals; Calcium Signaling; Cytochromes c; Dose-Response Relationship, Drug; Energy Metabolism; Fasting; Glucose; Glycolysis; In Vitro Techniques; Insulin; Insulin Secretion; Islets of Langerhans; Keto Acids; Metabolic Diseases; Mitochondria; Oxidation-Reduction; Oxygen; Protein Transport; Rats; Rats, Sprague-Dawley