Islet Number Rather Than Islet Size Is a Major Determinant of β- and α-Cell Mass in Humans

OBJECTIVE: The objective of the study was to clarify the relative contribution of islet number and islet size to β- and α-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/m(2)). Pancreatic sections were stained for insulin or glucagon, and fractional β-cell area (%BCA) and α-cell area (%ACA) were measured. Islet number and islet size as well as β-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 β- and α-cell mass in humans. Interindividual difference in islet number may contribute to susceptibility to development of glucose intolerance.