Intestinal and Systemic Effects of Oral Insulin Supplementation in Rats After Weaning

Abstract

Oral insulin has intestinal trophic effects in suckling animals. In mice, lower glucose and lipid levels may be seen when oral insulin is given after the weaning period. The purpose of the present study is to examine local and systemic effects of oral insulin supplementation in rats in the postweaning period. Immediately after weaning, Sprague-Dawley rats received either drinking water (controls) or oral insulin in their drinking water (1 U/ml) for either 1 week or 6 weeks. Intestinal mucosal parameters (bowel and mucosal weight, mucosal DNA and protein) and histological changes were examined in all study groups. Glucose levels were monitored weekly, and at the end of the study, blood levels of glucose, lipids, and insulin were measured in the fasting state. After 1 week of insulin supplementation, mucosal weight in duodenum and jejunum as well as jejunal DNA content were significantly higher in insulin-supplemented rats compared to controls. Duodenal circumference and villus height in jejunum were significantly higher in insulin-supplemented rats compared to controls on both day 7 and day 42. Total cholesterol levels were significantly lower in the study group compared with the controls. We conclude that oral insulin supplementation exerts intestinal trophic effects, as well as systemic effects in the postweaning period in rats.

Oral Insulin Enhances Intestinal Regrowth Following Massive Small Bowel Resection in Rat

“…We have also shown that oral INS had a trophic gut effect that was evidenced by increased bowel circumference, mucosal weight, mucosal DNA, and villous height. The maximal changes were observed in the first week of INS treatment, and most significant changes were observed in the proximal intestine (27). The results of the present study add to the evidence that oral INS has a trophic effect on the remaining small bowel following massive small bowel resection.…”

Effect of Oral Insulin on Diabetes-Induced Intestinal Mucosal Growth in Rats

“…Several in vitro and in vivo experiments have demonstrated that insulin and insulin-like growth factors enhance proliferation and diminish apoptosis in epithelial cells. We have previously observed similar effects of oral insulin on intestinal epithelial cell turnover in young rats after weaning [15], in rats after bowel resection [16] or adult rats after intestinal damage [17,18]. In contrast to these experiments, the current data suggest that OI supplementation in normal non-stressed adult rats exerts a mild inhibitory effect on microscopic intestinal mucosal parameters.…”

“…Group A-control rats (CONTR) were injected with vehicle and fed with regular chow diet; Group B-control rats were fed regular chow diet and water containing insulin at a concentration of 1u/1 ml as we described previously [15][16][17][18]; Group C-diabetic rats (DIAB) were injected with one dose of streptozotocin (STZ); Group D-DIAB-INS rats were injected with STZ and were treated with oral insulin similar to group B.…”

“…A fact that insulin is present in human and pig colostrum and mature milk and insulin receptors are present on both luminal and basolateral membranes of the enterocyte may suggest a potential role of insulin in small intestinal growth and development [14]. We have previously shown that OI supplementation exerts trophic effects on the intestinal mucosa, decreases the total cholesterol level, and does not cause hypoglycemia in the postweaning period in rats [15]. The insulin concentration of 1u/ml in drinking water had an optimal effect in this study.…”

Oral Insulin Up-regulates Toll-like Receptor 4 Expression and Enhances Intestinal Recovery Following Lipopolysaccharide-induced Gut Injury in a Rat

“…In another study, these researchers have demonstrated that insulin activates the brush border membrane hydrolases in rat immature intestine by binding the hormone to its intestinal receptor and indirect triggering of the transcription of hydrolases genes and possibly by changes in intracellular polyamine concentrations [16]. We have recently shown that oral insulin supplementation exerts intestinal trophic effects, as well as systemic effects in rats when administered up to 6 weeks beyond the suckling period [17]. Since insulin has trophic gut effects, we hypothesized that insulin may have a beneficial effect on gut growth and recovery in different gastrointestinal disorders.…”