Effect of insulin deprivation on muscle mitochondrial ATP production and gene transcript levels in type 1 diabetic subjects.
OBJECTIVE: Muscle mitochondrial dysfunction occurs in many insulin-resistant states, such as type 2 diabetes, prompting a hypothesis that mitochondrial dysfunction may cause insulin resistance. We determined the impact of insulin deficiency on muscle mitochondrial ATP production by temporarily depri...
| Publicado en: | Diabetes Vol. 56; no. 11; pp. 2683 - 2690 |
|---|---|
| Autores principales: | , , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
American Diabetes Association
Nov2007
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=105825371&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 105825371 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00121797 1G6 jtl: Diabetes issn: 00121797 maglogo: N pubinfo: dt: Nov2007 vid: 56 iid: 11 pid: 1367 pub: American Diabetes Association place: Arlington, Virginia artinfo: ui: 105825371 2009713048 NLM17660267 105825371 ppf: 2683 ppct: 7 formats: tig: atl: Effect of insulin deprivation on muscle mitochondrial ATP production and gene transcript levels in type 1 diabetic subjects. aug: au: Karakelides H Asmann YW Bigelow ML Short KR Dhatariya K Coenen-Schimke J Kahl J Mukhopadhyay D Nair KS affil: Division of Endocrinology and Metabolism and Endocrine Research Unit, Mayo Clinic, 200 First St. SW, Joseph 5-194, Rochester, MN 55905, USA. sug: subj: Adenosine Triphosphate Metabolism Diabetes Mellitus, Type 1 Metabolism Diabetes Mellitus, Type 1 Insulin Deficiency Mitochondria Metabolism Muscle, Skeletal Metabolism RNA Adult Biochips Blood Glucose Metabolism Body Mass Index Diabetes Mellitus, Type 1 Blood DNA Probes Energy Metabolism Fatty Acids Blood Polymerase Chain Reaction Adult: 19-44 years ab: OBJECTIVE: Muscle mitochondrial dysfunction occurs in many insulin-resistant states, such as type 2 diabetes, prompting a hypothesis that mitochondrial dysfunction may cause insulin resistance. We determined the impact of insulin deficiency on muscle mitochondrial ATP production by temporarily depriving type 1 diabetic patients of insulin treatment. RESEARCH DESIGN AND METHODS: We withdrew insulin for 8.6 +/- 0.6 h in nine C-peptide-negative type 1 diabetic subjects and measured muscle mitochondrial ATP production and gene transcript levels (gene array and real-time quantitative PCR) and compared with insulin-treated state. We also measured oxygen consumption (indirect calorimetry); plasma levels of glucagon, bicarbonate, and other substrates; and urinary nitrogen. RESULTS: Withdrawal of insulin resulted in increased plasma glucose, branched chain amino acids, nonesterified fatty acids, beta-hydroxybutyrate, and urinary nitrogen but no change in bicarbonate. Insulin deprivation decreased muscle mitochondrial ATP production rate (MAPR) despite an increase in whole-body oxygen consumption and altered expression of many muscle mitochondrial gene transcripts. Transcript levels of genes involved in oxidative phosphorylation were decreased, whereas those involved in vascular endothelial growth factor (VEGF) signaling, inflammation, cytoskeleton signaling, and integrin signaling pathways were increased. CONCLUSIONS: Insulin deficiency and associated metabolic changes reduce muscle MAPR and expression of oxidative phosphorylation genes in type 1 diabetes despite an increase in whole-body oxygen consumption. Increase in transcript levels of genes involved in VEGF, inflammation, cytoskeleton, and integrin signaling pathways suggest that vascular factors and cell proliferation that may interact with mitochondrial changes occurred. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|