Linear Correlation Between -Cell Mass and Body Weight Throughout the Lifespan in Lewis Rats Role of -Cell Hyperplasia and Hypertrophy

and did not change significantly from month 1 to 20 of life. Cross-sectional area of individual ␤-cells increased progressively in the initial months, remained stable from month 7 to 15, and increased again on month 20. The estimated number of ␤-cells per pancreas, calculated as the ratio of total ␤-cell mass to individual ␤-cell mass, tripled from month 1 to 7 but did not change significantly thereafter. ␤-Cell mass increased ~8 times from month 1 to 20 (month 1, 2.04 ± 0.28 mg; month 20, 15.5 ± 2.32 mg; ANOVA, P < 0.001) and showed a strong and significant linear correlation with body weight (r = 0.98, P < 0.001). In summary, we have shown that ␤-cell repli-cation was maintained throughout the lifespan in normal rats, clearly establishing that the ␤-cell birth rate does not fall to 0, even in very old rats. ␤-Cell mass increased throughout the lifespan, closely matching the increment in total body weight at any time point. This increment was selective for ␤-cells, since the growth of the endocrine non–␤-cell mass was limited to the initial months of life. Both ␤-cell hypertrophy and hyperplasia contributed to increased ␤-cell mass in young animals, but only ␤-cell hypertrophy was responsible for the increased ␤-cell mass found in old animals. This study provides a global perspective for understanding the dynamics of ␤-cell mass in young, adult, and aged animals. T he ␤-cell mass present in the pancreas plays an essential role in determining the amount of insulin that is secreted, and it can be regulated to maintain euglycemia in various metabolic conditions (1,2). Increased ␤-cell mass has been consistently observed when islets must meet an increased metabolic demand in obesity (3,4), pregnancy (5), partial pancreatectomy (6), glucose infusion (7), or islet transplantation (8). Conversely, a reduction in ␤-cell volume has been reported in chronically hypoglycemic animals bearing transplantable insulinomas (9,10). Although changes in ␤-cell mass have been studied for years, important questions still remain about their regulation (11). ␤-Cell mass is determined by the size and number of ␤-cells, and the number of ␤-cells depends on the balance among ␤-cell neogenesis, ␤-cell replication, and ␤-cell death. It is generally accepted that in the fetal period, most ␤-cells are formed by differentiation from precursor cells and that after birth, most new ␤-cells result from replication of pre-existing ␤-cells (12). Therefore, in the postnatal period, the balance between ␤-cell replication and …