Fatty acids do not activate UCP2 in pancreatic beta cells: comparison with UCP1.
UCP2 is expressed in pancreatic beta cells where its postulated uncoupling activity will modulate glucose-induced changes in ATP/ADP ratio and insulin secretion. The consequences of UCP2 over/underexpression on beta-cell function has mainly been studied in the basal state; however, a UCP has no uncoupling activity unless stimulated by fatty acids and/or reactive oxygen species. Here, UCP2 was overexpressed in INS-1 cells and parameters reflecting mitochondrial coupling measured in the basal state and after stimulation by fatty acids. For comparison, UCP1 was expressed to similar levels and the same parameters measured. Neither UCP1 expression nor UCP2 overexpression modified basal or glucose-stimulated metabolic changes. Upon addition of fatty acids, UCP1-expressing cells displayed the expected mitochondrial uncoupling effect, while UCP2 did not elicit any measurable change in mitochondrial function. Taken together, our data demonstrate that, in pancreatic beta-cells, UCP2 has no uncoupling activity in the basal state or after fatty acid stimulation.
Galetti
Sandrine
S
Department of Cell Physiology and Metabolism, Medical Faculty, University of Geneva, 1 rue Michel Servet, 1211, Geneva 4, Switzerland.
Sarre
Alexandre
A
Perreten
Hélène
H
Produit-Zengaffinen
Nathalie
N
Muzzin
Patrick
P
Assimacopoulos-Jeannet
Françoise
F
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D007473:Ion Channels; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins; D010101:Oxygen Consumption; D051381:Rats; D014475:Uncoupling Agents / Q000378:metabolism*; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2
D005227:Fatty Acids; D007328:Insulin; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604371:UCP1 protein, human; C000604389:UCP2 protein, human; C000604373:Ucp1 protein, rat; C000604391:Ucp2 protein, rat; D014475:Uncoupling Agents; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate