Excess glucose intake induces accelerated beta-cell polyploidization in normal mice: a possible deleterious effect.

Normal nondiabetic homozygous and heterozygous littermates of db/db diabetes-prone mice (seven/group) were fed a 5% solution of glucose as their sole source of liquid for 10 wk. Controls (seven/group) drank tap water, and both groups received stock diet ad libitum. Body weights, tail lengths, food and fluid consumption were recorded throughout the study, and plasma and urine glucose were measured during wk 10. The total caloric intake, including the glucose solution drunk by some of the mice, was not significantly different among the four groups. No differences in plasma or urine glucose were detected. Total-body dry weight, water and lipid were measured, and pancreata were analyzed for beta-cell polyploidy by a combination of Feulgen cytophotometry and nuclear size analysis. The percentage of polyploid beta-cells was significantly higher in the animals that drank glucose than in those that drank water and was independent of both genotype and growth indices attributable to genotype. The greater polyploidization was interpreted as reflecting premature aging of the beta-cell population. It was hypothesized that such glucose-induced premature aging in animals with a genetically restricted potential for beta-cell proliferation could contribute to the precipitation of overt diabetes.