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Hals 2012 Biochem Biophys Res Commun

From Bioblast
Publications in the MiPMap
Hals IK, Ogata H, Pettersen E, Ma Z, Björklund A, Skorpen F, Egeberg KW, Grill V (2012) Marked over expression of uncoupling protein-2 in beta cells exerts minor effects on mitochondrial metabolism. Biochem Biophys Res Commun 423:259-64.

» PMID: 22634308

Hals IK, Ogata H, Pettersen E, Ma Z, Bjoerklund A, Skorpen F, Egeberg KW, Grill V (2012) Biochem Biophys Res Commun

Abstract: Evidence is conflicting as to the impact of elevated levels of uncoupling protein-2 (UCP-2) on insulin-producing beta cells. Here we investigated effects of a fourfold induction of UCP-2 protein primarily on mitochondrial parameters and tested for replication of positive findings at a lower level of induction. We transfected INS-1 cells to obtain a tet-on inducible cell line. A 48 h exposure to 1 μg/ml of doxycycline (dox) induced UCP-2 fourfold (424 ± 113%, mean ± SEM) and 0.1 μg/ml twofold (178 ± 29%, n = 3). Fourfold induced cells displayed normal viability (MTT, apoptosis), normal cellular insulin contents and, glucose-induced insulin secretion (+27 ± 11%) as well as D-[U-(14)C]-glucose oxidation (+5 ± 9% at 11 mM glucose). Oxidation of [1-(14)C]-oleate was increased from 4088 to 5797 fmol/μg prot/2h at 3.3 mM glucose, p< 0.03. Oxidation of L-[(14)C(U)]-glutamine was unaffected. Induction of UCP-2 did not significantly affect measures of mitochondrial membrane potential (Rhodamine 123) or mitochondrial mass (Mitotracker Green) and did not affect ATP levels. Oligomycin-inhibited oxygen consumption (a measure of mitochondrial uncoupling) was marginally increased, the effect being significant in comparison with dox-only treated cells, p< 0.05. Oxygen radicals, assessed by dichlorofluorescin diacetate, were decreased by 30%, p< 0.025.Testing for the lower level of UCP-2 induction did not reproduce any of the positive findings. A fourfold induction of UCP-2 was required to exert minor metabolic effects. These findings question an impact of moderately elevated UCP-2 levels in beta cells as seen in diabetes. Keywords: Uncoupling protein-2, Insulin secretion, Fatty acid oxidation, INS-1 cells

O2k-Network Lab: NO Trondheim Grill V


Labels: MiParea: Respiration, Genetic knockout;overexpression 


Tissue;cell: Islet cell;pancreas;thymus 

Enzyme: Uncoupling protein  Regulation: Coupling efficiency;uncoupling, Fatty acid  Coupling state: LEAK, OXPHOS 

HRR: Oxygraph-2k