The recently established pancreatic β-cell line MIN6 retains the ability to secrete insulin in response to physiological glucose concentrations. To investigate the role of glucose transport and phosphorylation in glucose- stimulated insulin secretion by β-cells, MIN6 cells were stably transfected with a rabbit GLUT1 glucose transporter cDNA or a rat hexokinase I cDNA cloned in an expression vector. Overexpression of GLUT1 increased 3-O- methylglucose uptake, but did not alter either glucose utilization or glucose-stimulated insulin secretion. In contrast, clones overexpressing hexokinase I exhibited enhanced glucose-stimulated insulin secretion at glucose concentrations below 10 mM with a concomitant increase in glucose utilization. Maximal insulin secretion as well as the maximal rate of glucose utilization were not altered in these clones. Insulin secretion stimulated by 2-ketoisocaproate, a non-glucose secretagogue, was not affected by hexokinase I expression. These results strongly suggest that the glucose phosphorylating step, but not glucose transport step, regulates glucose-stimulated insulin secretion by modulating the glycolytic rate in the β-cell.
|Number of pages||7|
|Journal||Journal of Biological Chemistry|
|Publication status||Published - 1994 Jan 28|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology