Control of Insulin Secretion by Cytochrome c and Calcium Signaling in Islets with Impaired Metabolism
Autor: | Austin M. Rountree, Sarah A. White, Francis Kim, Dan S. Luciani, Ian R. Sweet, Jared Radtke, Mark Lisowski, Adam S. Neal, Christiane S. Hampe, Norma O. Rizzo |
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Rok vydání: | 2014 |
Předmět: |
medicine.medical_specialty
medicine.medical_treatment chemistry.chemical_element Stimulation In Vitro Techniques Mitochondrion Calcium Biochemistry Rats Sprague-Dawley Islets of Langerhans Metabolic Diseases Internal medicine Insulin Secretion medicine Animals Insulin Glycolysis Calcium Signaling Molecular Biology Calcium signaling Dose-Response Relationship Drug biology Cytochrome c Cytochromes c Fasting Cell Biology Metabolism Keto Acids Mitochondria Rats Oxygen Protein Transport Glucose Endocrinology chemistry biology.protein Energy Metabolism Oxidation-Reduction |
Zdroj: | Journal of Biological Chemistry. 289:19110-19119 |
ISSN: | 0021-9258 |
Popis: | 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. |
Databáze: | OpenAIRE |
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