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Dietary non-digestible carbohydrates promote L-cell differentiation in the proximal colon of rats

  • Patrice D. Cani (a1), Sophie Hoste (a1), Yves Guiot (a2) and Nathalie M. Delzenne (a1)
Abstract

One of the challenges in type 2 diabetes treatment is to ensure pancreas functionality with gut peptides such as glucagon-like peptide-1 (GLP-1). We have recently shown that the endogenous GLP-1 production is promoted by dietary non-digestible carbohydrates (oligofructose), the higher GLP-1 secretion could participate in the control of obesity and associated disorders. This experimental study was designed to highlight the mechanisms of endogenous increase of GLP-1 following non-digestible carbohydrate feeding. Male Wistar rats were fed a standard diet (70·4 g/100 g total carbohydrates; controls) or the same diet supplemented with oligofructose (10 g/100 g diet) for 4 weeks. GLP-1-producing L-cells of the colon were quantified by immunohistochemistry. GLP-1 was quantified by ELISA, and proglucagon, neurogenin 3 and NeuroD mRNA were measured in the colon by quantitative RT–PCR. The number of GLP-1-expressing cells was doubled in the proximal colon of oligofructose-treated rats, a phenomenon correlated with the increase in proglucagon mRNA and peptide content in the tissue. Moreover, oligofructose increased the number of enteroendocrine L-cells in the proximal colon by a mechanism involving up-regulation of two differentiation factors: neurogenin 3 and NeuroD. It is the first demonstration that nutrients fermented in the gut may promote L-cell differentiation in the proximal colon, a phenomenon contributing to a higher endogenous GLP-1 production. These results suggest a new mechanism by which dietary fibres may lower food intake and fat mass development.

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Corresponding author
*Corresponding author: Prof. Nathalie M. Delzenne, fax +32 2 764 73 59, email delzenne@pmnt.ucl.ac.be
References
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Archer BJ, Johnson SK, Devereux HM, Baxter AL (2004) Effect of fat replacement by inulin or lupin-kernel fibre on sausage patty acceptability, post-meal perceptions of satiety and food intake in men. Br J Nutr 91, 591599.
Backhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, Semenkovich CF & Gordon JI (2004) The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A 101, 1571815723.
Brubaker PL & Drucker DJ (2004) Minireview: Glucagon-like peptides regulate cell proliferation and apoptosis in the pancreas, gut, and central nervous system. Endocrinology 145, 26532659.
Bryant MG, Bloom SR, Polak JM, Hobbs S, Domschke W, Domschke S, Mitznegg P, Ruppin H & Demling L (1983) Measurement of gut hormonal peptides in biopsies from human stomach and proximal small intestine. Gut 24, 114119.
Cani PD, Dewever C & Delzenne NM (2004) Inulin-type fructans modulate gastrointestinal peptides involved in appetite regulation (glucagon-like peptide-1 and ghrelin) in rats. Br J Nutr 92, 521526.
Cani PD, Daubioul CA, Reusens B, Remacle C, Catillon G & Delzenne NM (2005 a) Involvement of endogenous glucagon-like peptide-1(7–36) amide on glycaemia-lowering effect of oligofructose in streptozotocin-treated rats. J Endocrinol 185, 457465.
Cani PD, Neyrinck AM, Maton N & Delzenne NM (2005 b) Oligofructose promotes satiety in rats fed a high-fat diet: involvement of glucagon-like Peptide-1. Obes Res 13, 10001007.
Cani PD, Joly E, Horsmans Y & Delzenne NM (2006 a) Oligofructose promotes satiety in healthy human: a pilot study. Eur J Clin Nutr 60, 567572.
Cani PD, Knauf C, Iglesias MA, Drucker DJ, Delzenne NM & Burcelin R (2006 b) Improvement of glucose tolerance and hepatic insulin sensitivity by oligofructose requires a functional glucagon-like Peptide 1 receptor. Diabetes 55, 14841490.
Deacon CF, Knudsen LB, Madsen K, Wiberg FC, Jacobsen O & Holst JJ (1998) Dipeptidyl peptidase IV resistant analogues of glucagon-like peptide-1 which have extended metabolic stability and improved biological activity. Diabetologia 41, 271278.
Dhanvantari S, Seidah NG & Brubaker PL (1996) Role of prohormone convertases in the tissue-specific processing of proglucagon. Mol Endocrinol 10, 342355.
Dumas ME, Barton RH, Toye A, et al. (2006) Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice. Proc Natl Acad Sci USA 103, 1251112516.
Dumoulin V, Dakka T, Plaisancie P, Chayvialle JA & Cuber JC (1995) Regulation of glucagon-like peptide-1-(7–36) amide, peptide YY, and neurotensin secretion by neurotransmitters and gut hormones in the isolated vascularly perfused rat ileum. Endocrinology 136, 51825188.
Eissele R, Goke R, Willemer S, Harthus HP, Vermeer H, Arnold R & Goke B (1992) Glucagon-like peptide-1 cells in the gastrointestinal tract and pancreas of rat, pig and man. Eur J Clin Invest 22, 283291.
Fujita Y, Cheung AT & Kieffer TJ (2004) Harnessing the gut to treat diabetes. Pediatr Diabetes 5, Suppl. 2, 5769.
Gradwohl G, Dierich A, LeMeur M & Guillemot F (2000) Neurogenin3 is required for the development of the four endocrine cell lineages of the pancreas. Proc Natl Acad Sci U S A 97, 16071611.
Hodin R (2000) Maintaining gut homeostasis: the butyrate-NF-kappaB connection. Gastroenterology 118, 798801.
Holst JJ (2004) On the physiology of GIP and GLP-1. Horm Metab Res 36, 747754.
Karaki S, Mitsui R, Hayashi H, Kato I, Sugiya H, Iwanaga T, Furness JB & Kuwahara A (2006) Short-chain fatty acid receptor, GPR43, is expressed by enteroendocrine cells and mucosal mast cells in rat intestine. Cell Tissue Res 324, 353360.
Knauf C, Cani PD, Perrin C, et al. (2005) Brain glucagon-like peptide-1 increases insulin secretion and muscle insulin resistance to favor hepatic glycogen storage. J Clin Invest 115, 35543563.
Le Blay G, Michel C, Blottiere HM & Cherbut C (1999) Prolonged intake of fructo-oligosaccharides induces a short-term elevation of lactic acid-producing bacteria and a persistent increase in cecal butyrate in rats. J Nutr 129, 22312235.
Mariadason JM, Barkla DH & Gibson PR (1997) Effect of short-chain fatty acids on paracellular permeability in Caco-2 intestinal epithelium model. Am J Physiol 272, G705G712.
Mariadason JM, Rickard KL, Barkla DH, Augenlicht LH & Gibson PR (2000) Divergent phenotypic patterns and commitment to apoptosis of Caco-2 cells during spontaneous and butyrate-induced differentiation. J Cell Physiol 183, 347354.
Massimino SP, McBurney MI, Field CJ, Thomson AB, Keelan M, Hayek MG & Sunvold GD (1998) Fermentable dietary fiber increases GLP-1 secretion and improves glucose homeostasis despite increased intestinal glucose transport capacity in healthy dogs. J Nutr 128, 17861793.
Meier JJ, Nauck MA, Kranz D, Holst JJ, Deacon CF, Gaeckler D, Schmidt WE & Gallwitz B (2004) Secretion, degradation, and elimination of glucagon-like peptide 1 and gastric inhibitory polypeptide in patients with chronic renal insufficiency and healthy control subjects. Diabetes 53, 654662.
Moody AJ (1980) Gut glucagon-like immunoreactants. Clin Gastroenterol 9, 699709.
Nilsson U & Nyman M (2005) Short-chain fatty acid formation in the hindgut of rats fed oligosaccharides varying in monomeric composition, degree of polymerisation and solubility. Br J Nutr 94, 705713.
Nyman M (2002) Fermentation and bulking capacity of indigestible carbohydrates: the case of inulin and oligofructose. Br J Nutr 87, S163S168.
Orskov C, Holst JJ, Knuhtsen S, Baldissera FG, Poulsen SS & Nielsen OV (1986) Glucagon-like peptides GLP-1 and GLP-2, predicted products of the glucagon gene, are secreted separately from pig small intestine but not pancreas. Endocrinology 119, 14671475.
Piche T, des Varannes SB, Sacher-Huvelin S, Holst JJ, Cuber JC & Galmiche JP (2003) Colonic fermentation influences lower esophageal sphincter function in gastroesophageal reflux disease. Gastroenterology 124, 894902.
Pratt VC, Tappenden KA, McBurney MI & Field CJ (1996) Short-chain fatty acid-supplemented total parenteral nutrition improves nonspecific immunity after intestinal resection in rats. JPEN J Parenter Enteral Nutr 20, 264271.
Reimer RA & McBurney MI (1996) Dietary fiber modulates intestinal proglucagon messenger ribonucleic acid and postprandial secretion of glucagon-like peptide-1 and insulin in rats. Endocrinology 137, 39483956.
Reimer RA, Thomson AB, Rajotte RV, Basu TK, Ooraikul B & McBurney MI (1997) A physiological level of rhubarb fiber increases proglucagon gene expression and modulates intestinal glucose uptake in rats. J Nutr 127, 19231928.
Roberfroid MB & Delzenne NM (1998) Dietary fructans. Annu Rev Nutr 18, 117143.
Schonhoff SE, Giel-Moloney M & Leiter AB (2004) Minireview: Development and differentiation of gut endocrine cells. Endocrinology 145, 26392644.
Schwitzgebel VM, Scheel DW, Conners JR, Kalamaras J, Lee JE, Anderson DJ, Sussel L, Johnson JD & German MS (2000) Expression of neurogenin3 reveals an islet cell precursor population in the pancreas. Development 127, 35333542.
Shroyer NF, Wallis D, Venken KJ, Bellen HJ & Zoghbi HY (2005) Gfi1 functions downstream of Math1 to control intestinal secretory cell subtype allocation and differentiation. Genes Dev 19, 24122417.
Sjolund K, Sanden G, Hakanson R & Sundler F (1983) Endocrine cells in human intestine: an immunocytochemical study. Gastroenterology 85, 11201130.
Tappenden KA, Drozdowski LA, Thomson AB & McBurney MI (1998) Short-chain fatty acid-supplemented total parenteral nutrition alters intestinal structure, glucose transporter 2 (GLUT2) mRNA and protein, and proglucagon mRNA abundance in normal rats. Am J Clin Nutr 68, 118125.
Whelan K, Efthymiou L, Judd PA, Preedy VR & Taylor MA (2006) Appetite during consumption of enteral formula as a sole source of nutrition: the effect of supplementing pea-fibre and fructo-oligosaccharides. Br J Nutr 96, 350356.
Yamashita K, Itakura M & Kawai K (1984) Effects of fructo-oligosaccharides on blood glucose and serum lipids in diabetic subjects. Nutr Res 4, 961966.
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British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
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