Change search
ReferencesLink to record
Permanent link

Direct link
Diabetes reduces beta-cell mitochondria and induces distinct morphological abnormalities, which are reproducible by high glucose in vitro with attendant dysfunction
Karolinska Institutet.
Karolinska Institutet.
University of Uppsala.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Histology and Cell Biology.
Show others and affiliations
2012 (English)In: Islets, ISSN 1938-2014, Vol. 4, no 3, 233-242 p.Article in journal (Refereed) Published
Abstract [en]

We investigated the impact of a diabetic state with hyperglycemia on morphometry of beta-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 nondiabetic 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.

Place, publisher, year, edition, pages
2012. Vol. 4, no 3, 233-242 p.
Keyword [en]
diabetes, mitochondria, electron microscopy, islet transplantation, insulin secretion, K+-ATP channel opener, glucotoxicity
National Category
Endocrinology and Diabetes
URN: urn:nbn:se:umu:diva-61993DOI: 10.4161/isl.20516ISI: 000307119900007OAI: diva2:576170
Available from: 2012-12-12 Created: 2012-12-04 Last updated: 2013-10-25Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Larsson-Nyren, Gerd
By organisation
Histology and Cell Biology
Endocrinology and Diabetes

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 54 hits
ReferencesLink to record
Permanent link

Direct link