UCP-3 is expressed in human islets.

<p>A Human UCP-2, UCP-3 and α-tubulin mRNA expression in human islets. B Human islets were cultured at 5.5 or 11 mM glucose, and total protein extracts were analyzed on a western blot using UCP-3 antibodies. The intensities of the protein signal were quantified by scanning of images; blots for UCP-3 and β-actin is shown for one representative experiment. Data are expressed as means±SE, n = 3, * <i>p</i><0.05. C UCP-3 is expressed in human pancreatic islets, where it colocalizes with mitochondria. A representative layer of human pancreata is depicted showing UCP-3, mitochondria and overlay. Images were acquired using confocal microscope and imaged at x63 magnification, bar = 20 µm.</p

UCP3 over expression in human islets increases glucose-stimulated insulin secretion.

<p>A Western blot analysis of UCP-3 expression in transduced islets. B Isolated human pancreatic islets were cultured on extracellular matrix-coated dishes and transduced with adenoviruses expressing control virus (luciferase, Luc), UCP-3 or dnUCP-2. Basal and stimulated insulin secretion indicate the amount secreted during 1-hour incubations at 2.8 (basal) and 16.7 mM (stimulated) glucose following the 2-day culture period after transduction, normalized to whole islet insulin content. C Stimulatory index denotes the amount of stimulated divided by the amount of basal insulin secretion. Data represent results of two different experiments from two different organ donors in quadruplicate. Results are means±SE, *p<0.05 compared to control.</p

Dominant negative UCP-2 enhances insulin secretion in human islets.

<p>A Levels of UCP-2 protein in human islets following adenoviral misexpression of dn-UCP-2 (+) or GFP (−). B DnUCP-2 increases mitochondrial membrane potential. Human islets grown on extracellular-matrix-coated slides were transduced with Ad-dnUCP-2 or Ad-GFP. Mitochondrial membrane potential was detected by live staining with JC-1, and the JC-1 and islet cell area were measured using Image-Pro Plus software. Bar graph shows the percentage of JC-1 (area) divided by total islet area (<i>t</i>-test; *, <i>p</i><0.05 relative to control). C Human islets were transduced with Ad-dnUCP-2 (▪) or Ad-GFP (□, control) and cultured in suspension at 5.5 mM glucose before perifusion. Islets were perifused at 4 mM and 16 mM glucose and insulin concentrations were measured every 4 min. Results are of four independent experiments using four separate human islet donors. Data are presented as means±SE and analyzed by <i>t</i>-test, *, <i>p</i><0.001.</p