β-cell mass and turnover in humans: effects of obesity and aging

Abstract

Objective: We sought to establish β-cell mass, β-cell apoptosis, and β-cell replication in humans in response to obesity and advanced age.

Research design and methods: We examined human autopsy pancreas from 167 nondiabetic individuals 20-102 years of age. The effect of obesity on β-cell mass was examined in 53 lean and 61 obese subjects, and the effect of aging was examined in 106 lean subjects.

Results: β-Cell mass is increased by ~50% with obesity (from 0.8 to 1.2 g). With advanced aging, the exocrine pancreas undergoes atrophy but β-cell mass is remarkably preserved. There is minimal β-cell replication or apoptosis in lean humans throughout life with no detectable changes with obesity or advanced age.

Conclusions: β-Cell mass in human obesity increases by ~50% by an increase in β-cell number, the source of which is unknown. β-Cell mass is well preserved in humans with advanced aging.

Figure 1

Representative insulin (brown)-hematoxylin immunohistochemistry of pancreas (original magnification ×100). Examples of lean (male, 28 years of age, BMI 23.4) (A), obese (male, 44 years of age, BMI 33.6) (B), and elderly (male, 91 years of age, BMI 16.2; female, 100 years of age, BMI 24.9) (C and D) subjects. The fractional pancreatic insulin-positive area/pancreas parenchymal area, average islet size, and islet density are all modestly increased in obesity (B) compared with lean subjects (A). Pancreatic fat was also increased in obesity (B). Whereas atrophy, fibrosis, and fat accumulation are typical in the exocrine pancreas of elderly individuals (C and D), compared with a younger population (A), islet structure was remarkably maintained (C and D). As a result, fractional β-cell area/pancreas parenchymal area was increased in elderly vs. younger individuals (C and D vs. A). Scale bars, 200 μm. (A high-quality digital representation of this figure is available in the online issue.)

Figure 2

Fractional β-cell area (A), estimated pancreas parenchymal volume (B), and computed β-cell mass (C) in lean and obese nondiabetic subjects. The pancreatic fractional β-cell area was ∼30% greater in the obese vs. the lean group (A). Estimated pancreas parenchymal volume (see research design and methods) was ∼15% greater in the obese vs. the lean subjects (B). In consequence, the computed mean β-cell mass was ∼50% higher in obese subjects (0.8 g in lean and 1.2 g in obese) (C). However, there was no increase in mean individual β-cell size in obese subjects (D).

Figure 3

Correlation between β-cell mass and BMI in nondiabetic humans. There was a significant positive correlation between β-cell mass and BMI.

Figure 4

Pancreatic fractional β-cell area (A) and computed β-cell mass (B) in lean nondiabetic subjects from 20 to 100 years of age. Pancreatic fractional β-cell area increased with age (A), but when β-cell mass was calculated from pancreatic parenchyma (Supplementary Fig. 1), β-cell mass remained constant to advanced age (B). The mean individual β-cell cross-sectional area (C) and β-cell nuclear diameter (D) both increased with age.