Uncoupling protein 2 and islet function.
Stressors such as chronic hyperglycemia or hyperlipidemia may lead to insufficient insulin secretion in susceptible individuals, contributing to type 2 diabetes. The molecules mediating this effect are just beginning to be identified. Uncoupling protein (UCP)-2 may be one such negative modulator of insulin secretion. Accumulating evidence shows that beta-cell UCP2 expression is upregulated by glucolipotoxic conditions and that increased activity of UCP2 decreases insulin secretion. Mitochondrial superoxide has been identified as a posttranslational regulator of UCP2 activity in islets; thus, UCP2 may provide protection to beta-cells at one level while simultaneously having detrimental effects on insulin secretion. Interestingly, the latter appears to be the dominant outcome, because UCP2 knockout mice display an increased beta-cell mass and retained insulin secretion capacity in the face of glucolipotoxicity.
Chan
Catherine B
CB
Department of Biomedical Sciences, University of Prince Edward Island, Charlottetown, Prince Edward, Canada. cchan@upei.ca
Saleh
Monique C
MC
Koshkin
Vasilij
V
Wheeler
Michael B
MB
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D000078790:Insulin Secretion; D007473:Ion Channels; D007515:Islets of Langerhans / Q000502:physiology*; D026901:Membrane Transport Proteins / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000502:physiology*; D009747:Nutritional Physiological Phenomena; D017382:Reactive Oxygen Species / Q000378:metabolism; D000071246:Uncoupling Protein 2
D007328:Insulin; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C000604389:UCP2 protein, human; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2