Abstract
Aims/hypothesisType 2 diabetes is characterised by reduced beta cell mass (BCM). However, it remains uncertain whether the reduction in BCM in type 2 diabetes is due to a decrease in size or number of beta cells. Our aim was to examine the impact of beta cell size and number on islet morphology in humans with and without type 2 diabetes.MethodsPancreas samples were obtained from 64 Japanese adults with (n = 26) and without (n = 38) type 2 diabetes who underwent pancreatectomy. Using pancreatic tissues stained for insulin, we estimated beta cell size based on beta cell diameter. Beta cell number was estimated from the product of fractional beta cell area and pancreas volume divided by beta cell size. The associations of beta cell size and number with islet morphology and metabolic status were examined.ResultsBoth beta cell size (548.7 ± 58.5 vs 606.7 ± 65.0 μm3, p < 0.01) and number (5.10 × 108 ± 2.35 × 108 vs 8.16 × 108 ± 4.27 × 108, p < 0.01) were decreased in participants with type 2 diabetes compared with those without diabetes, with the relative reduction in beta cell number (37%) being greater than for beta cell size (10%). Beta cell number but not size was positively correlated with BCM in participants with and without type 2 diabetes (r = 0.97 and r = 0.98, both p < 0.01) and negatively correlated with HbA1c (r = −0.45, p < 0.01).Conclusions/interpretationBoth beta cell size and number were reduced in participants with type 2 diabetes, with the relative reduction in beta cell number being greater. Decrease in beta cell number appears to be a major contributor to reduced BCM in type 2 diabetes.Graphical abstract
Highlights
Type 2 diabetes is characterised by reduced beta cell mass (BCM) [1]
E r = -0.19 p = 0.14 f r = -0.45 p
Because the reduction in beta cell number was greater than the reduction in beta cell size (37% vs 10%), beta cell number is likely to have a major role with respect to the reduced BCM in type 2 diabetes
Summary
Type 2 diabetes is characterised by reduced beta cell mass (BCM) [1]. BCM has been shown to decrease by approximately 20–65% in individuals with type 2 diabetes [1, 3, 4], the precise mechanism remains uncertain. Increased beta cell apoptosis in individuals with type 2 diabetes has been reported as one of the underlying mechanisms of reduced BCM [3]; recent studies have suggested beta cell dedifferentiation and/or degranulation. Rodent models of type 2 diabetes have shown decreased BCM but increased beta cell size [7]. In a previous study on Europids, beta cell number rather than size was increased in non-diabetic individuals with insulin resistance or obesity [8, 9]. Using our previously published data [10], we here aimed to estimate the relative contribution of beta cell size and number to the reduction of BCM in individuals with type 2 diabetes
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