Transport and Metabolism in the Gastrointestinal Tract of Diabetic Animals:a study involving lean and (ob/ob) mice

Abstract

The aim of this work was to characterize changes that may occur in the size of the small intestine, the transport and metabolism of monosaccharides, the activity of disaccharidases in the small intestine and transport of amino acids, in response to the (ob/ob) syndrome. The main adaptive response of the small intestine to the (ob/ob) syndrome was an increase in size due to proportionate increases in muscle and mucosa. The response was clearly an effect of hyperphagia, but, unlike other hyperphagic states, the size of the intestine did not regress when food consumption returned to normal. There was little effect of the (ob/ob) syndrome on the transepithelial transport of glucose or the unidirectional influx of α-MG across the brush border when the data were expressed per unit weight of intestine. Similarly, glucose metabolism (μmol/hr per g dry wt.) by the small intestine was largely unaffected by genotype, and there was no general elevation of disaccharides activities per mg protein in obese mice compared with lean mice. These results provide little evidence of an effect of hyper-insulinaemia or hyperphagia on the activity of these systems in the (ob/ob) mouse. However, because of mucosal hyperplasia in the small intestine of (ob/ob) mice, the total capacity to transport monosaccharides and total disaccharidase activities were increased. Despite mucosal hyperplasia in the (ob/ob) mouse, there was no increase in the total capacity of the small intestine to transport leucine; indeed, transepithelial transport of leucine, but not influx across the brush border, was depressed in 10-week-old (ob/ob) mice when expressed per unit weight of tissue. The depressed transepithelial leucine transport may be due to the severe hyperinsulinaemia seen in 10-week-old (ob/ob) mice, and the effect may represent an adaptive response at the basolateral membrane.