Difference between revisions of "Ma 2012 Islets"
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|year=2012 | |year=2012 | ||
|journal=Islets | |journal=Islets | ||
|abstract=We investigated the impact of a diabetic state with hyperglycemia on morphometry of β 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 2–3 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 I–IV), OPA 1 and glucose-induced insulin release. | |abstract=We investigated the impact of a diabetic state with hyperglycemia on morphometry of β 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 2–3 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 I–IV), 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. | 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. | ||
|keywords=Diabetes, | |keywords=Diabetes, Electron microscopy, Glucotoxicity, Insulin secretion, Islet transplantation, K+-ATP channel opener | ||
|mipnetlab=NO Trondheim Grill V | |mipnetlab=NO Trondheim Grill V | ||
}} | }} | ||
| Line 14: | Line 14: | ||
|area=Respiration, mt-Structure;fission;fusion, Exercise physiology;nutrition;life style, Pharmacology;toxicology | |area=Respiration, mt-Structure;fission;fusion, Exercise physiology;nutrition;life style, Pharmacology;toxicology | ||
|organism=Rat | |organism=Rat | ||
|tissues=Kidney, Islet | |tissues=Kidney, Islet cell;pancreas;thymus | ||
|diseases=Diabetes | |diseases=Diabetes | ||
|topics=Ion;substrate transport | |topics=Ion;substrate transport | ||
Latest revision as of 14:52, 13 March 2015
| Ma Z, Wirstroem T, Borg H, Larsson-Nyren G, Hals IK, Bondo-Hansen J, Grill V, Bjoerklund A (2012) Diabetes reduces β-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 β 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 2–3 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 I–IV), 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. • Keywords: Diabetes, Electron microscopy, Glucotoxicity, Insulin secretion, Islet transplantation, K+-ATP channel opener
• O2k-Network Lab: NO Trondheim Grill V
Labels: MiParea: Respiration, mt-Structure;fission;fusion, Exercise physiology;nutrition;life style, Pharmacology;toxicology
Pathology: Diabetes
Organism: Rat Tissue;cell: Kidney, Islet cell;pancreas;thymus
Regulation: Ion;substrate transport
Coupling state: OXPHOS
HRR: Oxygraph-2k
