Glucose induces and leptin decreases expression of uncoupling protein-2 mRNA in human islets.
Elevated islet uncoupling protein-2 (UCP-2) impairs beta-cell function and UCP-2 may be increased in clinical obesity and diabetes. We investigated the effects of glucose and leptin on UCP-2 expression in isolated human islets. Human islets were incubated for 24 h with glucose (5.5-22 mmol/l)+/-leptin (0-10 nmol/l). Some islet batches were incubated at high (22 mmol/l), and subsequently lower (5.5 mmol/l), glucose to assess reversibility of effects. Leptin effects on insulin release were also measured. Glucose dose-dependently increased UCP-2 expression in all islet batches, maximally by three-fold. This was not fully reversed by subsequently reduced glucose levels. Leptin decreased UCP-2 expression by up to 75%, and maximally inhibited insulin release by 47%, at 22 mmol/l glucose. This is the first report of UCP-2 expression in human islets and provides novel evidence of its role in the loss of beta-cell function in diabetes.
Brown
James E P
JE
Diabetes Research Group, Division of Biomedical Science, School of Applied Sciences, University of Wolverhampton, Wulfruna Street, WV1 1SB, Wolverhampton, UK.
Thomas
Steven
S
Digby
Janet E
JE
Dunmore
Simon J
SJ
D000704:Analysis of Variance; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007473:Ion Channels; D007515:Islets of Langerhans / Q000187:drug effects* / Q000502:physiology; D020738:Leptin / Q000494:pharmacology*; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D000071246:Uncoupling Protein 2
D007328:Insulin; D007473:Ion Channels; D020738:Leptin; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D012333:RNA, Messenger; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2; D005947:Glucose