Impact of uncoupling protein-2 overexpression on ...
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Citation
| Title | Impact of uncoupling protein-2 overexpression on proinsulin processing |
| Author(s) | N. Kashemsant, C. Chan |
| Journal | Journal of Molecular Endocrinology |
| Date | 2006 |
| Volume | 37 |
| Issue | 3 |
| Start page | 517 |
| End page | 526 |
| Abstract | Hyperproinsulinemia is observed in type 2 diabetic patients. We hypothesized that the induction of uncoupling protein-2 (UCP2) would impair processing of proinsulin to mature insulin and potentially contribute to hyperproinsulinemia, based on the evidence that hormone processing is an ATP-dependent process and UCP2 up-regulation can suppress cellular ATP production. UCP2 was overexpressed (UCP2-OE) by twofold in INS-1 cells by means of plasmid transfection. Although UCP2-OE reduced glucose-stimulated insulin secretion and cellular ATP content, no effects on proinsulin processing, as measured by western blotting, were observed. To increase the demand for insulin, we then cultured UCP2-OE and control INS-1 cells in medium containing 20 mM KCl for 24 h. High K(+) markedly reduced glucose-stimulated insulin secretion from control cells, indicating inability of cells to meet secretory demand. Independent of UCP2 expression, high K(+) reduced preproinsulin mRNA expression but had no effect on ATP content despite increasing ATP synthase expression. In UCP2-OE cells, high K(+)decreased total cellular insulin species content and increased the ratio of proinsulin to insulin, indicating an impairment of processing. We conclude that UCP2-OE can negatively impact proinsulin processing, possibly by ATP-dependent alteration of the granule environment or reduction of Ca(2+)availability, particularly when cells are chronically stimulated to secrete insulin. |
| DOI | 10.1677/jme.1.02091 |
| ISSN | 0952-5041 |
Using APA 6th Edition citation style.
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