Linear correlation between β-cell mass and body weight throughout the lifespan in Lewis rats. Role of β-cell hyperplasia and hypertrophy

Abstract

We determined the β-cell replicative rate, β-cell apoptosis, cross-sectional β-cell area, and pancreatic β-cell mass throughout the entire postweaning lifespan (months 1, 3, 7, 10, 15, and 20) of Lewis rats. β-Cell replication was progressively reduced in the initial months of life but remained stable after month 7 (month 1, 0.99 ± 0.10%; month 3, 0.24 ± 0.04%; month 7, 0.12 ± 0.02%; month 10, 0.14 ± 0.02%; month 15, 0.10 ± 0.03%; month 20, 0.13 ± 0.03%; analysis of variance [ANOVA], P < 0.001). β-Cell apoptosis was low and did not change significantly from month 1 to 20 of life. Cross-sectional area of individual β-cells increased progressively in the initial months, remained stable from 7 to 15, and increased again on month 20. The estimated number of β-cell per pancreas, calculated as the ratio of total β-cell mass to individual β-cell mass, tripled from month 1 to 7 but did not change significantly thereafter. β-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 β-cell replication was maintained throughout the lifespan in normal rats, clearly establishing that the β-cell birth rate does not fall to 0, even in very old rats. β-Cell mass increased throughout the lifespan, closely matching the increment in total body weight in any time point. This increment was selective for β-cells, since the growth of the endocrine non-β-cell mass was limited to the initial months of life. Both β-cell hypertrophy and hyperplasia contributed to increased β-cell mass in young animals, but only β-cell hypertrophy was responsible for the increased β-cell mass found in old animals. This study provides a global perspective for understanding the dynamics of β-cell mass in young, adult, and aged animals.