Small human islets comprised of moreβ-cells with higher insulin content than large islets

Abstract

For the past 30 y, data have suggested that unique islet populations exist, based on morphology and glucose sensitivity. Yet little has been done to determine the mechanism of these functional differences. The purpose of this study was to determine whether human islets were comprised functionally unique populations, and to elucidate a possible mechanism. Islets or pancreatic sections from 29 human donors were analyzed. Islets were isolated and measured for insulin secretion, cell composition and organization, insulin and glucagon granule density and insulin content. Insulin secretion was significantly greater in small compared with large islets. In sectioned human pancreata, β-cells comprised a higher proportion of the total endocrine cells in small islets (63%) than large islets (39%). A higher percentage of β-cells in small islets contacted blood vessels (44%) compared with large islets (31%). Total insulin content of isolated human islets was significantly greater in the small (1323 ± 512 μIU/IE) compared with large islets (126 ± 48 μIU/IE). There was less immunostaining for insulin in the large islets from human pancreatic sections, especially in the core of the islet, compared with small islets. The results suggest that differences in insulin secretion between large and small islets may be due to a higher percentage of β-cells in small islets with more β-cells in contact with blood vessels and a higher concentration of insulin/β-cell in small islets.

Filtration is a time-efficient option to Histopaque, providing good-quality islets in mouse islet isolation

“…In this regard, Fujita et al (2011) reported that large islets secreted less insulin than small islets per islet equivalent. This is consistent with the fact that, in human pancreata, there is a higher proportion of beta cells in small islets (39 %) than in large islets (63 %), and its closer contact with blood vessels may affect insulin secretion (Farhat et al 2013). However, in a more recent study by Nam and colleagues (2010) the islets with the highest SI value had between 100 and 150 lm diameter in a heterogeneous population, which are in the size range of all methods.…”

“…Some articles have reported the superiority of rodent and human islets under 100-125 lm against large islets in in vitro and in vivo function (MacGregor et al 2006;Lehman et al 2007;Farhat et al 2013). In this regard, Fujita et al (2011) reported that large islets secreted less insulin than small islets per islet equivalent.…”

Dynamics of glucose-induced insulin secretion in normal human islets

“…In these 22 control experiments, total islet insulin content, measured at the end of the perifusions, averaged 6,500 Ϯ 660 ng/chamber (range 2,430 Ϫ13,580), which would correspond to 17.8 Ϯ 1.7 ng/islet (range 7.3-32.1), a value within the range of contents published by many laboratories (1,3,11,19,47).…”

“…Although islet hand-picking may be required for valid metabolic or gene expression analyses, a nonselective procedure has the advantage of being more representative of the whole islet population in situ. Small islets, which are not spontaneously hand-picked, have been reported to secrete proportionally more insulin than large islets, with (19) or without (42) a greater stimulation index. Another study using 200 islets per perifusion chamber has also reported excellent consistency between the responses of 12 preparations (2).…”

Assessment of β-Cell Function

“…The capillaries surrounding islets have numerous fenestrations that facilitate nutrient exchange [ 11 ]. Heterogeneity in β-cell numbers between islets may be relevant to insulin secretion [ 12 ]. The activity of β-cells is synchronized both within and across islets.…”