Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Liu, S; Okada, T; Assmann, A; Soto, J; Liew, CW; Bugger, H; Shirihai, OS; Abel, ED; Kulkarni, RN.
Insulin signaling regulates mitochondrial function in pancreatic beta-cells.
PLoS One. 2009; 4(11): e7983-e7983.
Doi: 10.1371/journal.pone.0007983
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- Co-Autor*innen der Med Uni Graz
- Bugger Heiko Matthias
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- Abstract:
- Insulin/IGF-I signaling regulates the metabolism of most mammalian tissues including pancreatic islets. To dissect the mechanisms linking insulin signaling with mitochondrial function, we first identified a mitochondria-tethering complex in beta-cells that included glucokinase (GK), and the pro-apoptotic protein, BAD(S). Mitochondria isolated from beta-cells derived from beta-cell specific insulin receptor knockout (betaIRKO) mice exhibited reduced BAD(S), GK and protein kinase A in the complex, and attenuated function. Similar alterations were evident in islets from patients with type 2 diabetes. Decreased mitochondrial GK activity in betaIRKOs could be explained, in part, by reduced expression and altered phosphorylation of BAD(S). The elevated phosphorylation of p70S6K and JNK1 was likely due to compensatory increase in IGF-1 receptor expression. Re-expression of insulin receptors in betaIRKO cells partially restored the stoichiometry of the complex and mitochondrial function. These data indicate that insulin signaling regulates mitochondrial function and have implications for beta-cell dysfunction in type 2 diabetes.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cyclic AMP-Dependent Protein Kinases - metabolism
- Cytosol - metabolism
- Diabetes Mellitus, Type 2 - metabolism
- Glucokinase - metabolism
- Humans -
- Insulin - metabolism
- Insulin-Secreting Cells - cytology
- Insulin-Secreting Cells - metabolism
- Islets of Langerhans - cytology
- Mice -
- Mice, Knockout -
- Mitochondria - metabolism
- Phosphorylation -
- Receptor, Insulin - genetics
- Serine - chemistry
- Signal Transduction -