B-CELL SIZE INFLUENCES GLUCOSE-STIMULATED INSULIN-SECRETION

To determine whether the heterogeneous B-cell response to glucose is r elated to a different metabolic handling of this sugar, we have compar ed rat B-cells differing in their redox response to glucose stimulatio n. To this end, a population of B-cells showing increased NAD(P)H auto fluorescence after a 15-min exposure to 16.7 mM glucose was sorted fro m a population of B-cells that, under the very same conditions, failed to show detectable changes in basal NADP(H) autofluorescence. Insulin secretion was evaluated by a reverse hemolytic plaque assay in these two populations, referred to as high and low NAD(P)H, respectively. Af ter a 30-min stimulation by 16.7 mM glucose, both populations comprise d secreting B-cells and B-cells that did not release detectable amount s of insulin. However, the percentage of secreting B-cells and total i nsulin output were larger (P < 0.01-0.02) in the high- (77.9 +/- 6.5% and 141.7 +/- 27.4 mum2 x 10(3)) than in the low-NAD(P)H population (5 8.7 +/- 6% and 92.7 +/- 20.5 mum2 X 10(3)). The high-NAD(P)H populatio n also comprised B-cells that, on average, had a larger (P < 0.001) pr ofile area (142.9 +/- 2.3 mum2) than the B-cells of the low-NAD(P)H po pulation (118.6 +/- 1.5 mum2). Glucose-induced insulin secretion was s imilar in the high- and low-NAD(P)H group when cells of similar sizes were compared and increased similarly in the two populations as a func tion of B-cell size. Analysis of variance revealed that insulin secret ion was influenced (P < 0.005) by the size of B-cells and not by their NAD(P)H level. Size also influenced the protein biosynthesis of B-cel ls. These data show that the secretory and biosynthetic heterogeneity of B-cells is related to differences in their size rather than in thei r differential ability to activate their metabolism in the presence of glucose.