Number and ultrastructure of epithelial cells in crypts and villi along the streptozotocin-diabetic small intestine: a quantitative study on the effects of insulin and aldose reductase inhibition

Abstract

This study has quantified the effects of insulin treatment with and without aldose reductase inhibitor (ponalrestat) on intestinal epithelial cell morphology in streptozotocin-diabetic rats. Epithelial volumes, villous and microvillous surface areas and mean volumes of cells (and their nuclei) in crypts and villi were estimated in each of four segments and in the entire intestine. We derived total numbers of cells, quantified the ultrastructural features of average cells and explored variation along the intestine and between experimental groups. In crypts, insulin and ponalrestat had significant effects on cell number (reduced towards normal values) and size (volume and apex area increased beyond normal values). There were interaction effects between insulin and ponalrestat for cell volume and apex area (insulin producing more exaggerated effects when given without ponalrestat). On villi, insulin and ponalrestat returned cell numbers towards normal values but neither treatment normalised cell size or the number and area of microvilli per cell. Indeed, ponalrestat increased microvillous number and area beyond values found in untreated diabetic animals. Again, there were interaction effects between insulin and ponalrestat. Patterns of segmental variation seen in crypts of normal rats (values tending to be higher in proximal or mid-intestinal regions) were not preserved, and only some of the segmental differences seen on villi (higher values at proximal or mid-intestinal sites) were maintained during therapy. Apart from reducing the abnormally high numbers of cells in untreated diabetic rats, these results show that insulin and ponalrestat treatment fail to restitute epithelial cell morphology in the small intestines of experimental diabetic rats.

The effect of ileal interposition surgery on enteroendocrine cell numbers in the UC Davis type 2 diabetes mellitus rat

“…Stereological methods have previously been shown to be superior to traditional morphometric analysis using planar measurements of villus length [37] and is distinguished by producing absolute values of intestinal volume, surface area and the number of cells instead of ratios, thereby allowing for a better comparison between studies. Our estimates of total volume and surface area in the sham group are in line with previous findings from other experiments in laboratory rats [38][39][40][41].…”

Biomechanical and morphometric intestinal remodelling during experimental diabetes in rats

“…In this study, the blood glucose concentration was four to five times higher in diabetic rats than in non-diabetic rats. Many studies have shown that experimental Type 1 diabetes causes morphological, functional, and metabolic alterations in the small intestine [2,3,5,6,7,8,9,10,23]. The major findings in this study were that the opening angle and residual strain were lower in the duodenum and larger in the jejunum and ileum in diabetic rats compared to normal rats.…”

“…The main metabolic complications of diabetes are retinopathy, nephropathy and peripheral vasculopathy. Gastrointestinal (GI) by STZ is characterised by morphological GI remodelling such as proliferation of different layers, especially of the mucosa in the small intestine [5,6,7,8,9,10]. Because morphological remodelling of the small intestine occurs in diabetes, the biomechanical properties are also likely to change.…”

Honey - A Novel Antidiabetic Agent

“…Studies have documented a number of changes or alterations in the brush border membrane (BBM) fluidity in diabetes 56. These alterations (such as increased number and size of cells, increased number and area of microvilli per cell, enhanced activities of carbohydrate-hydrolyzing enzymes such as maltase, sucrase and trehalase as well as facilitated glucose absorption) may aggravate diabetes and its related complications 57-59. Besides alterations in the BBM fluidity, Bhor and Sivakami reported increased oxidative damage and non-enzymatic glycation in duodenum and jejunum of diabetic rats 56.…”