Islet number rather than islet size is a major determinant of α- And β-Cell mass in humans

Objective: The objective of the study was to clarify the relative contribution of islet number and islet size to α- and β-cell mass in humans. Research Design and Methods: We obtained the pancreas at autopsy from 72 Japanese adults with no history of diabetes or pancreatitis (aged 47 ± 12 years, body mass index 24.1 ± 5.0 kg/m²). Pancreatic sections were stained for insulin or glucagon, and fractional ±-cell area (%BCA) and β-cell area (%ACA) were measured. Islet number and islet size as well as ±-cell turnover were also quantified. Glycosylated hemoglobin measured within 1 year prior to death was obtained in 38 individuals. Results: There was considerable interindividual variation in islet density and mean islet size, with a significant negative correlation between the two (r = -0.25, P = .03). There were significant positive correlations between islet density and %BCA or %ACA (r = 0.63, P < .001, and r = 0.41, P = .001), whereas mean islet size correlated with neither of them. Islet density as well as %BCA, but not mean islet size, was negatively correlated with glycosylated hemoglobin (r=-0.37, P = .02, and r = -0.36, P = .03). Conclusion: The present study suggests that islet number rather than islet size is a major determinant of ±- and =-cell mass in humans. Interindividual difference in islet number may contribute to susceptibility to development of glucose intolerance.