Ma 2012 Islets
| Ma Z, Wirstroem T, Borg H, Larsson-Nyren G, Hals IK, Bondo-Hansen J, Grill V, Bjoerklund A (2012) Diabetes reduces Ξ²-cell mitochondria and induces distinct morphological abnormalities, which are reproducible by high glucose in vitro with attendant dysfunction. Islets V(4) - I(3) - (05-06/2012). |
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Ma Z, Wirstroem T, Borg H, Larsson-Nyren G, Hals IK, Bondo-Hansen J, Grill V, Bjoerklund A (2012) Islets
Abstract: We investigated the impact of a diabetic state with hyperglycemia on morphometry of Ξ² cell mitochondria and modifying influence of a K+-ATP channel opener and we related in vivo findings with glucose effects in vitro. For in vivo experiments islets from syngeneic rats were transplanted under the kidney capsule to neonatally streptozotocin-diabetic or non-diabetic recipients. Diabetic recipients received vehicle, or tifenazoxide (NN414), intragastrically for 9 weeks. Non-diabetic rats received vehicle. Transplants were excised 7 d after cessation of treatment (wash-out) and prepared for electron microscopy. Morphological parameters were measured from approx. 25,000 mitochondria. Rat islets were cultured in vitro for 2β3 weeks at 27 or 11 (control) mmol/l glucose. Transplants to diabetic rats displayed decreased numbers of mitochondria (-31%, p < 0.05), increased mitochondrial volume and increased mitochondrial outer surface area, p < 0.001. Diabetes increased variability in mitochondrial size with frequent appearance of mega-mitochondria. Tifenazoxide partly normalized diabetes-induced effects, and mega-mitochondria disappeared. Long-term culture of islets at 27 mmol/l glucose reproduced the in vivo morphological abnormalities. High-glucose culture was also associated with reduced ATP and ADP contents, reduced oxygen consumption, reduced signaling by MitoTracker Red and reduction of mitochondrial proteins (Complexes IβIV), OPA 1 and glucose-induced insulin release.
We conclude that (1) a long-term diabetic state leads to a reduced number of mitochondria and to distinct morphological abnormalities which are replicated by high glucose in vitro; (2) the morphological abnormalities are coupled to dysfunction; (3) K+-ATP channel openers may have potential to partly reverse glucose-induced effects. β’ Keywords: Diabetes, electron microscopy, glucotoxicity, insulin secretion, islet transplantation, K+-ATP channel opener
Labels: MiParea: Respiration, mt-Structure; fission; fusion"mt-Structure; fission; fusion" is not in the list (Respiration, Instruments;methods, mt-Biogenesis;mt-density, mt-Structure;fission;fusion, mt-Membrane, mtDNA;mt-genetics, nDNA;cell genetics, Genetic knockout;overexpression, Comparative MiP;environmental MiP, Gender, ...) of allowed values for the "MiP area" property., Exercise physiology; nutrition; life style"Exercise physiology; nutrition; life style" is not in the list (Respiration, Instruments;methods, mt-Biogenesis;mt-density, mt-Structure;fission;fusion, mt-Membrane, mtDNA;mt-genetics, nDNA;cell genetics, Genetic knockout;overexpression, Comparative MiP;environmental MiP, Gender, ...) of allowed values for the "MiP area" property., Pharmacology; toxicology"Pharmacology; toxicology" is not in the list (Respiration, Instruments;methods, mt-Biogenesis;mt-density, mt-Structure;fission;fusion, mt-Membrane, mtDNA;mt-genetics, nDNA;cell genetics, Genetic knockout;overexpression, Comparative MiP;environmental MiP, Gender, ...) of allowed values for the "MiP area" property.
Pathology: Diabetes 2"Diabetes 2" is not in the list (Aging;senescence, Alzheimer's, Autism, Cancer, Cardiovascular, COPD, Diabetes, Inherited, Infectious, Myopathy, ...) of allowed values for the "Diseases" property.
Organism: Rat Tissue;cell: Kidney, Islet Cell; Pancreas; Thymus"Islet Cell; Pancreas; Thymus" is not in the list (Heart, Skeletal muscle, Nervous system, Liver, Kidney, Lung;gill, Islet cell;pancreas;thymus, Endothelial;epithelial;mesothelial cell, Blood cells, Fat, ...) of allowed values for the "Tissue and cell" property.
Regulation: Ion&substrate transport"Ion&substrate transport" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property.
Coupling state: OXPHOS
HRR: Oxygraph-2k
