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Metabolic cross talk between the colon and the periphery: implications for insulin sensitivity: Sir David Cuthbertson Medal Lecture

  • M. Denise Robertson (a1)


Until recently, a glance at a standard undergraduate textbook would have given the impression that the colon was merely a storage organ for faeces and maybe something about the absorption of electrolytes and water. In reality, the colon is a highly-metabolically-active organ, the function of which has implications not only for the remainder of the digestive tract, but also for peripheral organs such as adipose tissue (AT), liver and skeletal muscle. The present review focuses on two distinct but complementary areas: (1) the metabolic adaptation that occurs following surgical removal of colonic tissue; (2) the effect of modulating the colon in situ in terms of postprandial metabolism, insulin sensitivity and disease risk. Work in these two areas points to the colon being important in modulating normal tissue insulin sensitivity. The role of fatty acids is central to the insulin sensitivity hypothesis. AT acts as a daily ‘buffer’ for fatty acids. However, following colonic resection there is an apparent change in AT function. There is an increase in the AT lipolysis rate, resulting in the release of excess fatty acids into the circulation and consequently the take up of excess fatty acids into skeletal muscle. This resultant increase in either storage of lipid or its oxidation would result in a reduction in insulin sensitivity. The insulin-sensitising effects of high-fibre diets are also related to changes in AT function and fatty acid metabolism, but manipulating colonic tissue in situ allows the mechanisms to be elucidated. This research area is an exciting one, involving the potential role of SCFA (the absorbed by-products of colonic bacterial fermentation) acting directly on peripheral tissues, following the recent identification of G-protein-coupled receptors specific for these ligands.

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Corresponding author

Corresponding author: Dr Denise Robertson, fax +44 14863 686401, email


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Adachi, M, Kitamura, K, Miyoshi, T, Narikiyo, T, Iwashita, K, Shiraishi, N, Nonoguchi, H & Tomita, K (2001) Activation of epithelial sodium channels by prostasin in Xenopus oocytes. Journal of the American Society of Nephrology 12, 11141121.
Adrian, TE, Savage, AP, Fuessl, HS, Wolfe, K, Besterman, HS & Bloom, SR (1987) Release of PYY after resection of small bowel, colon and pancreas in man. Surgery 100, 715719.
Akanji, AO, Bruce, MA & Frayn, KN (1989) Effect of acetate infusion on energy expenditure and substrate oxidation rates in non-diabetic and diabetic subjects. European Journal of Clinical Nutrition 43, 107115.
Aston, LM (2006) Glycaemic index and metabolic disease risk. Proceedings of the Nutrition Society 65, 125134.
Barbier, M, Vidal, H, Desreumaux, P, Dubuquoy, L, Bourreille, A, Colombel, JF, Cherbut, C & Galmiche, JP (2003) Overexpression of leptin mRNA in mesenteric adipose tissue in inflammatory bowel diseases. Gastroenterologie Clinique et Biologique 27, 987991.
Baxter, AJ, Coyne, T & McClintock, C (2006) Dietary patterns and metabolic syndrome – a review of the epidemiological evidence. Asia Pacific Journal of Clinical Nutrition 15, 134142.
Beck, B (1989) Gastric inhibitory polypeptide: a gut hormone with anabolic functions. Journal of Molecular Endocrinology 2, 169174.
Bertin, E, Arner, P, Bolinder, J & Hagstrom-Toft, E (2001) Action on glucagon and glucagon-like peptide 1 (7–36) amide on lipolysis in human subcutaneous adipose tissue. Journal of Clinical Endocrinology and Metabolism 86, 12291234.
Besterman, HS, Mallinson, CN, Modigliani, R, Christofides, ND, Pera, A, Ponti, V, Sarson, DL & Bloom, SR (1983) Gut hormones in inflammatory bowel disease. Scandinavian Journal of Gastroenterology 18, 845852.
Brighenti, F, Benini, L, Del Rio, D, Casiraghi, C, Pellegrini, N, Scazzina, F, Jenkins, DJ & Vantini, I (2006) Colonic fermentation of indigestible carbohydrates contributes to the second-meal effect. American Journal of Clinical Nutrition 83, 817822.
Brown, AJ, Goldsworthy, SM, Barnes, AA, Eilert, MM, Tcheang, L, Daniels, D et al. (2003) The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. Journal of Biological Chemistry 278, 1131211319.
Buchler, M, Malfertheiner, P, Eiberle, E, Friess, H, Nustende, R, Schusdziarra, V, Feurle, GE & Beger, HG (1988 a) Pancreatic trophism following colectomy in rats: the potential role of gastrointestinal hormones. Pancreas 3, 477483.
Buchler, M, Malfertheiner, P, Friess, H, Eiberle, E & Beger, HG (1988 b) Gut-peptide mediated adaptive response of the exocrine pancreas. Scandinavian Journal of Gastroenterology 151, Suppl., 114122.
Cammisotto, PG, Renaud, C, Gingras, D, Delvin, E, Levy, E & Bendayan, M (2005) Endocrine and exocrine secretion of leptin by the gastric mucosa. Journal of Histochemistry and Cytochemistry 53, 851860.
Capristo, E, Mingrone, G, Addolorato, G, Greco, AV & Gasbarrini, G (1999) Glucose metabolism and insulin sensitivity in inactive inflammatory bowel disease. Alimentary Pharmacology and Therapeutics 13, 209217.
Catena, C, Lapenna, R, Baroselli, S, Nadalini, E, Colussi, G, Novello, M, Favret, G, Melis, A, Cavarape, A & Sechi, L (2006) Insulin sensitivity in patients with primary aldosteronism: a follow-up study. Journal of Clinical Endocrinology and Metabolism 91, 34573463.
Christl, SU & Sceppach, W (1997) Metabolic consequences of total colectomy. Scandinavian Journal of Gastroenterology 222, Suppl., 2024.
Crouse, JR, Gerson, CD, DeCarli, LM & Lieber, CS (1968) Role of acetate in the reduction of plasma free fatty acids produced by ethanol in man. Journal of Lipid Research 9, 509512.
Evers, BM, Izukura, M, Townsend, CM, Uchida, T & Thompson, JC (1992) Neurotensin prevents intestinal mucosal hypoplasia in rats fed an elemental diet. Digestive Diseases and Sciences 37, 426431.
Ferchaud-Roucher, V, Pouteau, E, Piloquet, H, Zair, Y & Krempf, M (2005) Colonic fermentation from lactulose inhibits lipolysis in overweight subjects. American Journal of Physiology 289, E716E720.
Fukushima, K, Haneda, S, Funayama, Y, Watanabe, K, Kouyama, A, Takahashi, KI, Owaga, H, Shibata, C & Sasaki, I (2006) An approach to analyse mechanisms of intestinal adaptation following total proctocolectomy. Journal of Gastrointestinal Surgery 10, 662671.
Fukushima, K, Sasano, H, Sasaki, I, Nagura, H, Funayama, Y & Matsuno, S (1994) Increased expression of mineralocorticoid receptor in human ileum after total colectomy: immunohistochemical and immunoblotting studies. Tohoku Journal of Experimental Medicine 173, 383390.
Fukushima, K, Sato, S, Naito, H, Funayama, Y, Haneda, S, Shibata, C & Sasaki, I (2005) Comparative study of epithelial gene expression in the small intestine among total proctocolectomized, dietary sodium-depleted, and aldosterone infused rats. Journal of Gastrointestinal Surgery 9, 236244.
Fuller, PJ & Verity, K (1990) Mineralocorticoid receptor gene expression in the gastrointestinal tract: distribution and ontogeny. Journal of Steroid Biochemistry 36, 263267.
Goff, LM, Bell, JD, So, PW, Dornhorst, A & Frost, GS (2005) Veganism and its relationship with insulin resistance and intramyocellular lipid. European Journal of Clinical Nutrition 59, 291298.
Greenberg, GR, Buchan, AMJ, McLeod, RS, Preston, P & Cohen, Z (1989) Gut hormone profile after reconstructive surgery for ulcerative colitis. Gut 30, 17211730.
Hallonquist, H, Cima, RR, Klingensmith, ME, Purdy, MJ, Delpire, E, Zinner, MJ & Soybel, DI (1998) Selective increase in gastric mucosal mRNA encoding basolateral Na-K-2Cl cotransporter following ileostomy in the rat. Journal of Gastrointestinal Surgery 2, 238243.
Haneda, S, Fukushima, K, Funayama, Y, Shibata, C, Takahashi, K, Ogawa, H, Nagao, M, Watanabe, K & Sasaki, I (2006) Fecal stream is essential for adaptive induction of glucose-coupled sodium transport in the remnant ileum after total proctocolectomy. Journal of Gastrointestinal Surgery 10, 10511059.
Hill, G (1976) Ileostomy: Surgery, Physiology and Management. New York: Grune and Stratton.
Hong, YH, Nishimura, Y, Hishikawa, D, Tsuzuki, H, Miyahara, H, Gotoh, C et al. (2005) Acetate and propionate short chain fatty acids stimulate adipogenesis via GPCR43. Endocrinology 146, 50925099.
Huber, FX, Lucas, M, Stern, J, Hinz, U, Haack, D, Heuschen, U & Herfarth, C (2001) Changes in glucocorticoid and mineralocorticoid hormone levels due to compensation for ileostomy levels. International Journal of Surgical Investigation 2, 369375.
Kabir, M, Rizkalla, SW, Champ, M, Luo, J, Boillot, J, Bruzzo, F & Slama, G (1998 a) Dietary amylose-amylopectin starch content affects glucose and lipid metabolism in adipocytes of normal and diabetic rats. Journal of Nutrition 128, 3543.
Kabir, M, Rizkalla, SW, Quignard-Boulangé, A, Guerre-Millo, M, Boillot, J, Ardouin, B, Luo, J & Slama, G (1998 b) A high glycemic index starch diet affects lipid storage-related enzymes in normal and to a lesser extent in diabetic rats. Journal of Nutrition 128, 18781883.
Karmiris, K, Koutroubakis, IE, Xidakis, C, Polychronaki, M, Voudouri, T & Kouroumalis, EA (2006) Circulating levels of leptin, adiponectin, resistin, and ghrelin in inflammatory bowel disease. Inflammatory Bowel Diseases 12, 100105.
Kato, K, Sasano, H, Ohara, S, Sekine, H, Mochizuki, S, Mune, T, Yasuda, K, Nagura, H, Shimosegawa, T, Toyota, T & Krozowski, Z (1999) Co-expression of mineralocorticoid receptors and 11beta-hydroxysteroid dehydrogenase 2 in human gastric mucosa. Journal of Clinical Endocrinology and Metabolism 84, 25682573.
Kennedy, HJ, Sarson, DL, Bloom, SR & Truelove, SC (1982) Gut hormone responses in subjects with a permanent ileostomy. Digestion 24, 133136.
Kirsten, R, Nelson, K, Ruschendorf, U, Seger, W, Scholz, T & Kirsten, E (1977) Effects of aldosterone on lipid metabolism and renal oxygen consumption in the rat. Pflugers Archiv 368, 189194.
Koyama, K, Sasaki, I, Naito, H, Funayama, Y, Fukushima, K, Unno, M, Matsuno, S, Hayashi, H & Suzuki, Y (1999) Induction of an epithelial Na+ channel in the rat ileum after proctocolectomy. American Journal of Physiology 276, G779G784.
Kraus, D, Jager, J, Meier, B, Fasshauer, M & Klein, J (2005) Aldosterone inhibits uncoupling protein-1, induces insulin resistance and stimulates proinflammatory adipokines in adipocytes. Hormone and Metabolic Research 37, 455459.
Lee, SH & Hossner, KL (2002) Coordinate regulation of ovine adipose tissue gene expression by propionate. Journal of Animal Science 80, 28402849.
Lerer-Metzger, M, Rizkalla, SW, Luo, J, Champ, M, Kabir, M, Bruzzo, F, Bornet, F & Slama, G (1996) Effects of long-term low-glycaemic index starchy food on plasma glucose and lipid concentrations and adipose tissue cellularity in normal and diabetic rats. British Journal of Nutrition 75, 723732.
Lukish, J, Schwartz, MZ, Rushin, JM & Riordan, GP (1997) A comparison of the effect of growth factors on intestinal function and structure in short bowel syndrome. Journal of Pediatric Surgery 32, 16521655.
McGarry, JD (2002) Banting Lecture 2001: dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. Diabetes 51, 718.
Mata, A, Gomez de Segura, IA, Largo, C, Codesal, J & De Miguel, E (1997) Neurotensin increases intestinal adaptation and reduces enteroglucagon-like immunoreactivity after large-bowel resection in rats. European Journal of Surgery 163, 587593.
Medhus, AW, Bjornland, K, Emblem, R, Haug, E & Husebye, E (2001) Are patients with Hirschsprung's disease prediabetic? Metabolism 50, 13891390.
Morino, K, Petersen, KF & Shulman, GI (2006) Molecular mechanisms of insulin resistance in humans and their potential links with mitochondrial dysfunction. Diabetes 55, Suppl. 2, S9S15.
Nauck, MA, Siemsgluss, J, Orskov, C & Holst, JJ (1996) Release of glucagon-like peptide 1 (GLP-1 [7–36 amide]), gastric inhibitory polypeptide (GIP) and insulin in response to oral glucose after upper and lower intestinal resections. Zeitschrift für Gastroenterologie 34, 159166.
Palnaes Hansen, C, Andreasen, JJ & Holst, JJ (1997) The release of gastric inhibitory peptide, glucagon-like peptide-I, and insulin after oral glucose test in colectomized subjects. Scandinavian Journal of Gastroenterology 32, 473477.
Pawlak, DB, Kushner, JA & Ludwig, DS (2004) Effects of dietary glycaemic index on adiposity, glucose homoeostasis, and plasma lipids in animals. Lancet 364, 778785.
Pereira, MA, Jacobs, DR Jr, Pins, JJ, Raatz, SK, Gross, MD, Slavin, JL & Seaquist, ER (2002) Effect of whole grains on insulin sensitivity in overweight hyperinsulinemic adults. American Journal of Clinical Nutrition 75, 848855.
Quinones-Galvan, A & Ferrannini, E (1997) Renal effects of insulin in man. Journal of Nephrology 10, 188191.
Randle, PJ, Garland, PB, Hales, CN & Newsholme, EA (1963) The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet i, 785789.
Rittler, P, Scheifer, B, Demmelmair, H, Koletzko, B, Vogesar, M, Alpers, DH, Jauch, KW & Hartl, WH (2006) The effect of hyperglycemic hyperinsulinemia on small intestinal mucosal protein synthesis in patients after surgical stress. Journal of Parenteral and Enteral Nutrition 30, 97107.
Robertson, MD, Bickerton, AS, Dennis, AL, Vidal, H & Frayn, KN (2005 a) Insulin-sensitizing effects of dietary resistant starch and effects on skeletal muscle and adipose tissue metabolism. American Journal of Clinical Nutrition 82, 559567.
Robertson, MD, Bickerton, AST, Dennis, AL, Vidal, H & Frayn, KN (2005 b) Enhanced metabolic cycling in patients following colonic resection for ulcerative colitis. Journal of Clinical Endocrinology and Metabolism 90, 27472754.
Robertson, MD, Livesey, G, Hampton, SM & Mathers, JC (2000) Evidence for altered control of glucose disposal after total colectomy. British Journal of Nutrition 86, 813819.
Robertson, MD, Livesey, G, Morgan, LM, Hampton, SM & Mathers, JC (1999) The influence of the colon on postprandial glucagon-like peptide 1 (7–36) amide concentration in man. Journal of Endocrinology 161, 2531.
Robertson, MD & Mathers, JC (2000) Gastric emptying rate of solids is reduced in a group of ileostomy patients. Digestive Diseases and Sciences 45, 12851292.
Sato, S, Fukushima, K, Naito, H, Funayama, Y, Suzuki, T, Sasano, H, Krozowski, Z, Shibata, C & Sasaki, I (2005) Induction of 11beta-hydroxysteroid dehydrogenase type 2 and hyperaldosteronism are essential for enhanced sodium absorption after total colectomy in rats. Surgery 137, 7584.
Scheppach, W, Pomare, EW, Elia, M & Cummings, JH (1991) The contribution of the large intestine to blood acetate in man. Clinical Science 80, 177182.
Schmidt, BMW, Oehmer, S, Delles, C, Bratke, R, Schneider, MP, Klingbeil, A, Fleischmann, EH & Schmieder, RE (2003) Rapid nongenomic effects of aldosterone on human forearm vasculature. Hypertension 42, 156160.
Steffen, LM, Jacobs, DR Jr, Murtaugh, MA, Moran, A, Steinberger, J, Hong, CP & Sinaiko, AR (2003) Whole grain intake is associated with lower body mass and greater insulin sensitivity among adolescents. American Journal of Epidemiology 158, 243250.
Suokas, A, Kupari, M, Heikkila, J, Lindros, K & Ylikahri, R (1988) Acute cardiovascular and metabolic effects of acetate in men. Alcoholism, Clinical and Experimental Research 12, 5258.
Teufel, M, Kleeberg, J, Flach, A, Reifferscheid, P & Niessen, KH (1988) Late results following partial and total colectomy in infancy. Klinische Padiatrie 200, 3035.
Weickert, MO, Mohlig, M, Schofl, C, Arafat, AM, Otto, B, Viehoff, H, Koebnick, C, Kohl, A, Spranger, J & Pfeiffer, AF (2006) Cereal fiber improves whole-body insulin sensitivity in overweight and obese women. Diabetes Care 29, 775780.
Weyer, C, Foley, JE, Bogardus, C, Tataranni, PA & Pratley, RE (2000) Enlarged subcutaneous abdominal adipocyte size, but not obesity itself, predicts type II diabetes independent of insulin resistance. Diabetologia 43, 14981506.
Willis, S, Kisielinski, K, Klosterhalfen, B & Schumpelick, V (2002) Morphological and functional adaptation of the small intestine after colectomy and ileal pouch-anal anastomosis in rats. International Journal of Colorectal Disease 17, 8591.
Woo, ZH & Nygaard, K (1978) Small-bowel adaptation after colectomy in rats. Scandinavian Journal of Gastroenterology 13, 903910.
Wright, HK, Cleveland, JC, Tilson, MD & Herskovic, T (1969) Morphology and absorptive capacity of the ileum after ileostomy in man. American Journal of Surgery 117, 242245.
Xiong, Y, Miyamoto, N, Shibata, K, Valasek, MA, Motoike, T, Kedzierski, RM & Yanagisawa, M (2004) Short chain fatty acids stimulate leptin production in adipocytes through the g protein-coupled receptor GPR41. Proceedings of the National Academy of Sciences USA 100, 10451050.
Yki-Jarvinen, H (2002) Ectopic fat accumulation; an important cause of insulin resistance in humans. Journal of the Royal Society of Medicine 95, Suppl. 42, 3945.



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