Dietary Insulin Affects Leucine Aminopeptidase, Growth Hormone, Insulin-Like Growth Factor I and Insulin Receptors in the Intestinal Mucosa of Neonatal Pigs

Abstract

Background: Recent studies suggest that milk-borne insulin may regulate the development of the gastrointestinal tract in neonatal mammals. Objectives: To explore the mechanism by which milk-borne insulin affects gastrointestinal tract development, we examined the effect of dietary insulin on the expression levels of leucine aminopeptidase (LAP) and insulin-like growth factor I (IGF-I), as well as its effect on growth hormone (GH), IGF-I and insulin receptors in the small intestinal mucosa of neonatal pigs. Methods: Five piglets were anesthetized and sampled within 2–4 h after birth. They were not allowed to suckle and were used as newborn controls (group N). Ten other piglets from 5 litters were randomly divided into group M (n = 5), which was fed cow’s milk, and group MI (n = 5), which was fed cow’s milk and insulin (2.5 mg/l). Piglets in groups M and MI were artificially fed for 3 days and then sampled. Total RNA in their intestinal mucosa was extracted with Tripure reagents (Roche, USA). Reverse transcription PCR (RT-PCR) was used to semi-quantify mRNA levels of target genes and 18S rRNA was used in an RT-PCR system as an internal control. PCR products were loaded onto a 9% nondenaturing polyacrylamide gel. The gel was stained by silver staining agents. Digital photos were taken and the strength of the band areas was quantified using software. Results: The results showed that the DNA contents and LAP activity in the small intestines of the piglets in group MI were higher (p < 0.05) than in the piglets in group N. Compared with group M, piglets in group MI exhibited significantly increased expression levels of both insulin and GH receptor in the ileum, and LAP in the jejunum (p < 0.05); IGF-I receptor expression levels in both the jejunum and ileum were significantly decreased (p < 0.01 and p < 0.05, respectively), while IGF-I expression was unchanged (p > 0.05). Conclusion: Collectively, dietary insulin increased mRNA levels of insulin and GH receptor, which could help explain the effect of dietary insulin on receptor-mediated postnatal development of the small intestine. Dietary insulin suppressed IGF-I receptor expression, which may be the result of negative feedback caused when insulin binds to IGF-I receptors.

Insulin in Human Milk and the Use of Hormones in Infant Formulas

“…Only the MI group had significantly higher DNA contents and leucine aminopeptidase activity in the small intestines compared to controls. Also, compared with group M, piglets in group MI exhibited significantly increased expression levels of both insulin and GH receptor in the ileum, and leucine aminopeptidase in the jejunum [14] . Interestingly, in that study, IGF-1 receptor expression levels in both the jejunum and ileum were significantly decreased (p < 0.01 and p < 0.05, respectively), while IGF-1 expression was unchanged [14] .…”

“…Also, compared with group M, piglets in group MI exhibited significantly increased expression levels of both insulin and GH receptor in the ileum, and leucine aminopeptidase in the jejunum [14] . Interestingly, in that study, IGF-1 receptor expression levels in both the jejunum and ileum were significantly decreased (p < 0.01 and p < 0.05, respectively), while IGF-1 expression was unchanged [14] . In addition to its direct effects on the intestinal mucosa, insulin given orally affects the maturation of the pancreas and induces pancreatic amylase development in rats [15] .…”

Effect of dietary phytate and phytase on proteolytic digestion and growth regulation of broilers

“…The production and secretion of humoral messengers in the gut are dietdependent (Marks 1985;Boyd et al 2003;Huo et al 2006). The modification of the nutritional milieu within the lumen generated from nutrients or non-nutrient chemicals of diets can affect the concentration of hormones by direct or indirect action on the gut, via nervous reflexes, or changes to circulating metabolites in the blood.…”

Growth and development of adipose tissue and gut and related endocrine status during early growth in the pig: impact of low birth weight

“…Oral insulin (85 mU/ml) enhances the small intestine and mucosal mass and the activity of brush border lactase and maltase in pig neonates (Shulman, 1990;Shulman et al, 1992). Interestingly, oral insulin also enhances the expression of its own receptor in small intestine, which may explain the effect of dietary insulin on receptor-mediated postnatal development of the small intestine (Huo et al, 2006). In the adipose tissue of many mammalian species, including pigs, insulin stimulates the anabolic lipid metabolism pathways (Romsos et al, 1971b;Mills, 1999).…”