(12) found zero evidence of apoptosis in either diabetic or nondiabetic individuals

(12) found zero evidence of apoptosis in either diabetic or nondiabetic individuals. type 2 diabetes. This perspectives in diabetes article will present what we know and still need to know about the islets in type 2 diabetes. == Islet architecture in human pancreas. == The islets of most mammalian species have a nonrandom pattern with a core of -cells surrounded by a discontinuous mantle of non–cells one to three cells thick (2,3). However, islets of human and other primates have a more complex arrangement with many different islet profiles, including cloverleaf patterns. The profile differences have led to controversy about whether they actually have a mantle-core arrangement (3) or were random (46). In three dimensions, human islets can be considered as composites of several mantle-core subunits (7) or as lobulated with mantle-core lobules (3). In smaller islets, the rodent mantle core subunit arrangement is maintained, but in larger islets irregular fusion of such subunits are seen (Fig. 1). Most of the GW842166X non–cells are found along penetrations of islet vasculature between subunits and the periphery (3,4), thus maintaining a mantle-core arrangement. Histologically, islets in the type 2 diabetic pancreas do not appear to differ from those of the nondiabetic pancreas, except for the presence of amyloid, as discussed below. Many years ago, pathologists reported hydropic degeneration seen as vacuolization in islets from diabetic persons. This vacuolization was due to extraction during histological processing (8) of large glycogen stores accumulated during poor metabolic control; it is less commonly reported now that it is understood. Fibrosis, particularly along the islet microvasculature, has also been previously reported but has since been found to occur equally in nondiabetic pancreata (9). == FIG. 1. == Nonrandom distribution of glucagons-positive cells in human islets. In normal adult human pancreas, there is a nonrandom distribution of glucagon cells (brown) similar to that seen in rodents. In some small islets, glucagon cells form a mantle around a core of -cells while larger islets seemed composed of irregular subunits of mantle-core organization. Immunoperoxidase staining for glucagon (brown); hematoxylin. Magnification bar = 50 um. (Please seehttp://dx.doi.org/10.2337/db07-1842for a high-quality digital representation of this figure.) == Cell composition of human islets. == The -cell composition in human islets has been reported in a number of studies presented as percentage on the basis of cell number or cell volume, with ranges of 5275% in nondiabetic adults (1016). The measure of proportion is further complicated because the probability of seeing a nucleus in a 1-m optical section is higher in non–cells than in -cells since the nuclear volumes are comparable but the cell volume of -cells is more than twice that of non–cells. Unlike rodent islets, the islets within a single human pancreas are highly variable in composition (Fig. 1); there are occasional large islets seen with a majority of glucagon-positive cells (11,15), and islets from the pancreatic polypeptide (PP)-rich uncinate process are mainly PP cells, with -cells being only 32.7 7.8% as compared with 65.5 4.9% in the rest of pancreas (12). (Similar values have been reported by Stefan et al. [10].) Because of this variability within a pancreas, it is imperative that a large number of islets are measured. In our studies Rabbit polyclonal to KAP1 (S.B.-W.) using ultrastructural analysis to determine cell type and cell boundaries, we found 72.8 1.7% -cells/islet in islets isolated from 41 pancreata. However, in studies using laser-scanning confocal microscopy on fewer islets, the -cell number in islets was estimated to be 55% (25 islets/section, 5 pancreata) (5) or 53.9 2.5% (32 islets isolated from 6 pancreata) (6). Thus, for comparison of cell composition in islets from type 2 diabetic and nondiabetic pancreata, it is important to use GW842166X data from the same study. For example, by measuring cell volume, Butler et al. (16) found that islets from lean nondiabetic subjects have 52.0 4.1% -cells, but islets from lean diabetic subjects have only 38.0 3.9%; Yoon et al. (15) reported 59 10.3% and 68.8 12.2% for nondiabetic control subjects but 38.3 12.4% for diabetic subjects; and GW842166X Maclean and Ogilive (17) found 74.8% for nondiabetic subjects and 63% for diabetic subjects. Thus, in three studies,.