Structural and functional studies on the transformation of the intestinal mucosa in rats with experimental diabetes

Abstract

Twenty days after the onset of alloxan-induced diabetes, a villous hyperplasia has developed in the intestines of rats having free access to food. The transformation is characterised by a considerable increase in the area of the villous surface, caused by an enhanced mitotic activity in the crypts. The absorption of glucose or methionine by jejunal loops, whether expressed in terms of serosal area or villous area, is unchanged at this stage. On the other hand, the specific activity of certain disaccharidases and dipeptidases in crude mucosal homogenates is greater in diabetic animals, but quantitative histochemistry revealed no changes in the activities of alkaline phosphatase, leucine amino-peptidase and non-specific esterase in the individual enterocytes. Thus the biochemical changes may simply reflect the hyperplasia of the mucosa. The blood sugar level does not appear to be directly responsible for the mucosal transformation; however, the positive correlation between the daily food intake and the villus height suggests a role of hyperphagia and consequent increased luminal nutrition in the development of the hyperplasia.

Effects of the neonatal treatment with monosodium glutamate on myenteric neurons and the intestine wall in the ileum of rats

“…55 Moreover, hyperphagia is associated with hyperplastic changes to the mucosa in diabetic rats. 56 Other studies suggest that intestinal function is optimized in MSG-treated animals. More efficient fat absorption rates 10 and an increase in alkaline phosphatase activity, indicating intestinal fat absorption, 16,17,20,27 have been observed in mice and MSG-treated rats, respectively.…”

Diabetes mellitus and sugar transport across the brush‐border and basolateral membranes of rat jejunal enterocytes.

“…Early studies reported an enhanced sugar and amino acid absorption across the small intestine of the diabetic rat (Pauls & Drury, 1942;Axelrad, Lawrence & Hazlewood, 1970;Olsen & Rosenberg, 1970) and the involvement of mucosal hyperplasia in the adaptive response has been well documented (Schedl & Wilson, 1971;Lorenz-Meyer et al 1977). More recent work has revealed that diabetes has a stimulatory effect, independent of changes in mucosal weight, on those substrates which utilize the Na+ electrochemical gradient for movement across the brush border (Fedorak, Chang, Madara & Field, 1987;Debnam et al 1988).…”

“…The increased basolateral transport is retained during subsequent migration of cells along the upper reaches of the villus. The recruitment of normally immature enterocytes acts in concert with an increased anatomical surface area (Lorenz-Meyer et al 1977) to produce the enhanced absorption which is characteristic of this condition. The luminal and/or humoral signals which mediate the adaptive response are unknown, although the increased glucose uptake in vivo following pair-feeding of diabetic rats eliminates the involvement of hyperphagia.…”

“…The differential effect of diabetes on sucrase and alkaline phosphatase activity confirms and extends a previous study which showed that diabetes of 20 days duration had a proportionally greater effect on the activities of those brush-border enzymes involved in carbohydrate digestion. (Lorenz-Meyer et al 1977).…”

“…Mucosal hyperplasia has long been implicated in the response (Schedl & Wilson, 1971;Lorenz-Meyer, Thiel, Menge, Gottesburen & Riecken, 1977) and it appears that in diabetic rats a prolonged enterocyte lifespan, together with a greater enterocyte number, results in a higher proportion of functionally mature cells on the villus (Debnam & Ebrahim, 1990). Sugar transport across the intestinal epithelial cell involves sequential events at the brush-border membrane and basolateral membrane, and the increased maturity of the villus cell population in diabetes is reflected in an enhanced electrochemical gradient for Na+-sugar co-transport across the brush border (Debnam, Karasov & Thompson, 1988;Debnam & Ebrahim, 1989), and a greater density of hexose transporters at this site (Fedorak, Gershon & Field, 1989).…”