Insulin and intestinal epithelial cell proliferation

Abstract

SUMMARYThe effects of modification of the levels of endogenous plasma insulin on intestinal epithelial cell proliferation were investigated in rats maintained by total parenteral nutrition (TPN) using either a TPN diet that was high in glucose, or a low glucose (hypocaloric) TPN diet and in orally fed rats (normal and sham operated). The rats were put on their respective treatments for 7 days and were then injected with vincristine sulphate to arrest cells as they entered metaphase. Intestinal tissue was fixed for the determination of crypt cell production rate (CCPR) and blood plasma was taken for hormone radioimmunoassay. Sham operation had no effect on either plasma hormone levels or on CCPR. The standard TPN diet was associated with significantly reduced levels of gastrin, peptide YY and enteroglucagon. Gastrin and PYY were further reduced by the hypocaloric diet. However, plasma insulin was much increased in the TPN but not in the hypocaloric group. Small intestinal CCPR was reduced in the TPN groups, but no difference was observed between the standard and the low calorie TPN diets.The lack of difference in CCPR between the two TPN diets despite the massive elevation of plasma insulin strongly suggests that insulin does not have a substantial role in the control of gastrointestinal epithelial cell renewal.

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

“…Inhibitors of this enzyme prevent hyperplasia in STZ-diabetic rats [58]. However, recent evidence suggests that whilst insulin affects the expression of intestinal enzymes, it does not have a major role in regulating cell proliferation [9,17]. The latter could be mediated by insulin-like growth factors (IGFs), which share a number of actions and amino acid sequences with insulin and exhibit high levels of expression on crypt cells [14, 16, 2l, 26, 47].…”

Nutrient-induced intestinal adaption and its effect in obesity

“…Increasing the luminal nutrient content using a variety of experimental methods increases the cell proliferation rate, cell number, villi length and crypt depth [methods include: intestinal resection/transposition 11 , hyperphagic animals models, such as lactation 12 or cold exposure 13,14 ]. Whereas, the exclusion of luminal nutrients does the opposite [methods include: fasts 11 , surgical bypass 15,16 , hibernating animals 17 , total parenteral nutrition 18,19 ]. Moreover, this effect of luminal nutrients appears to be independent of body weight and systemic factors.…”