title: Nutrient-sensing mechanisms in the gut as therapeutic targets for diabetes.
abstract: The small intestine is traditionally viewed as an organ that mediates nutrient digestion and absorption. This view has recently been revised owing to the ability of the duodenum to sense nutrient influx and trigger negative feedback loops to inhibit glucose production and food intake to maintain metabolic homeostasis. Further, duodenal nutrient-sensing defects are acquired in diabetes and obesity, leading to increased glucose production. In contrast, jejunal nutrient sensing inhibits glucose production and mediates the early antidiabetic effect of bariatric surgery, and gut microbiota composition may alter intestinal nutrient-sensing mechanisms to regain better control of glucose homeostasis in diabetes and obesity in the long term. This perspective highlights nutrient-sensing mechanisms in the gut that regulate glucose homeostasis and the potential of targeting gut nutrient-sensing mechanisms as a therapeutic strategy to lower blood glucose concentrations in diabetes.
authors: Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
authors: Danna M
authors: DM
authors: Breen
authors: Brittany A
authors: BA
authors: Rasmussen
authors: Clémence D
authors: CD
authors: Côté
authors: V Margaret
authors: VM
authors: Jackson
authors: Tony K T
authors: TK
authors: Lam
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000378:metabolism* / Q000382:microbiology; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007421:Intestine, Small / Q000378:metabolism / Q000382:microbiology
chemical_list: D001786:Blood Glucose; D005947:Glucose
references: J Am Coll Nutr. 1988 Jun;7(3):241-7
references: 3392357
references: Cell Metab. 2009 Aug;10(2):99-109
references: 19656488
references: Diabetes. 1997 Apr;46(4):615-21
references: 9075801
references: Nat Med. 2010 Apr;16(4):392-5
references: 20376051
references: Diabetes. 2013 Apr;62(4):1074-83
references: 23248171
references: Trends Endocrinol Metab. 2012 Feb;23(2):49-55
references: 22169756
references: Diabetes. 2013 Jul;62(7):2380-5
references: 23434938
references: Am J Physiol. 1996 Jul;271(1 Pt 1):G62-7
references: 8760108
references: Dig Dis Sci. 1983 Sep;28(9):812-9
references: 6884167
references: J Clin Invest. 2012 Jan;122(1):4-12
references: 22214853
references: Pancreas. 2000 Oct;21(3):231-9
references: 11039466
references: Lancet. 2012 Jun 16;379(9833):2300-11
references: 22683132
references: Nature. 2008 Apr 24;452(7190):1012-6
references: 18401341
references: Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):16050-5
references: 21876150
references: Diabetes. 2008 Apr;57(4):836-40
references: 18184925
references: Obes Surg. 2010 Apr;20(4):506-8
references: 20127290
references: Gastroenterology. 1994 Nov;107(5):1259-69
references: 7926490
references: Regul Pept. 1996 Sep 9;65(2):101-7
references: 8884976
references: Diabetes. 2008 Jun;57(6):1470-81
references: 18305141
references: JAMA. 2008 Jan 23;299(3):316-23
references: 18212316
references: Nature. 2006 Dec 21;444(7122):1027-31
references: 17183312
references: Gut. 2012 Apr;61(4):543-53
references: 22110050
references: Diabetologia. 2013 Jun;56(6):1413-6
references: 23519462
references: Nature. 2001 Dec 13;414(6865):799-806
references: 11742412
references: Gastroenterology. 2012 Oct;143(4):913-6.e7
references: 22728514
references: Science. 2008 Jun 20;320(5883):1647-51
references: 18497261
references: FEBS Lett. 1993 Jan 18;316(1):48-52
references: 7678554
references: Am J Physiol Endocrinol Metab. 2011 Dec;301(6):E1184-90
references: 21917638
references: Cell Metab. 2008 Sep;8(3):201-11
references: 18762021
references: Obes Surg. 2011 Feb;21(2):231-7
references: 21086062
references: Diabetes Care. 2012 Jul;35(7):1420-8
references: 22723580
references: Gastroenterology. 1999 Jan;116(1):46-53
references: 9869601
references: Clin Pharmacol Ther. 2008 Feb;83(2):281-7
references: 17597711
references: Neurosci Lett. 2008 Mar 5;433(1):38-42
references: 18248897
references: PLoS One. 2012;7(6):e39748
references: 22768116
references: PLoS One. 2010 Aug 16;5(8):e12191
references: 20808947
references: Obesity (Silver Spring). 2010 May;18(5):904-10
references: 20134410
references: Ann Surg. 2004 Jan;239(1):1-11
references: 14685093
references: Brain Res. 2001 Jun 8;903(1-2):128-40
references: 11382396
references: Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1:4523-30
references: 20837534
references: Biochem J. 1984 Jun 1;220(2):345-60
references: 6146314
references: Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17391-6
references: 20855609
references: Gastroenterology. 1976 Apr;70(4):528-32
references: 767195
references: Cell Metab. 2006 Mar;3(3):153-65
references: 16517403
references: Dig Dis Sci. 1994 May;39(5):1014-24
references: 8174414
references: Am J Physiol Regul Integr Comp Physiol. 2012 Mar 15;302(6):R657-66
references: 22160540
references: Mol Syst Biol. 2008;4:219
references: 18854818
references: Diabetes. 2008 Oct;57(10):2603-12
references: 18519802
references: Am J Physiol Regul Integr Comp Physiol. 2004 Jan;286(1):R166-73
references: 14660477
references: Am J Physiol. 1995 Jul;269(1 Pt 2):R7-14
references: 7631905
references: Gastroenterol Clin Biol. 1979 Oct;3(10):755-62
references: 527783
references: Gastroenterology. 1992 May;102(5):1654-9
references: 1568575
references: Diabetes Metab Res Rev. 2011 Feb;27(2):113-9
references: 21294237
references: Nature. 2012 May 17;485(7398):S2-3
references: 22616094
references: Gastroenterology. 2009 Nov;137(5):1716-24.e1-2
references: 19706296
references: Proc Natl Acad Sci U S A. 2009 Feb 17;106(7):2365-70
references: 19164560
references: Gastroenterology. 2011 Nov;141(5):1720-7
references: 21704002
references: Histochemistry. 1978 Nov 24;58(1-2):23-31
references: 365836
references: Physiology (Bethesda). 2012 Oct;27(5):300-7
references: 23026753
references: Lancet. 1975 Nov 22;2(7943):1016-8
references: 53500
references: Am J Physiol. 1990 Dec;259(6 Pt 1):G1031-6
references: 2260658
references: Obesity (Silver Spring). 2011 Feb;19(2):380-7
references: 21030948
references: Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):4813-9
references: 20194735
references: Endocrinology. 2011 Aug;152(8):3018-29
references: 21673098
references: Am J Clin Nutr. 1999 Jan;69(1):6-12
references: 9925116
references: Science. 2005 Mar 25;307(5717):1909-14
references: 15790843
references: Physiol Rev. 1997 Jan;77(1):257-302
references: 9016304
references: Regul Pept. 2000 Mar 17;88(1-3):75-81
references: 10706955
references: Br J Nutr. 2012 Mar;107(5):621-30
references: 21781379
references: Am J Physiol. 1997 Apr;272(4 Pt 2):R1170-7
references: 9140017
references: Obes Surg. 2010 Nov;20(11):1530-5
references: 20803098
references: Gut. 2008 Mar;57(3):424-5
references: 18268057
references: J Clin Invest. 2007 Jan;117(1):13-23
references: 17200702
references: Nat Med. 2012 Jun;18(6):950-5
references: 22610279
references: Sci Transl Med. 2009 Nov 11;1(6):6ra14
references: 20368178
references: Gut. 1984 Apr;25(4):365-74
references: 6706215
references: Am J Physiol Gastrointest Liver Physiol. 2001 Oct;281(4):G907-15
references: 11557510
references: PLoS One. 2012;7(8):e42373
references: 22876318
references: Am J Physiol Gastrointest Liver Physiol. 2000 Aug;279(2):G295-303
references: 10915637
references: Physiol Rev. 1993 Oct;73(4):701-23
references: 8415924
references: Diabetes. 2011 Dec;60(12):3148-53
references: 21984583
references: Surg Obes Relat Dis. 2007 Mar-Apr;3(2):195-7
references: 17386401
references: N Engl J Med. 2012 Apr 26;366(17):1567-76
references: 22449319
references: Gastroenterology. 2012 Apr;142(4):834-843.e3
references: 22245844
references: Cell Metab. 2007 Aug;6(2):99-104
references: 17681145
references: Metabolism. 2012 Sep;61(9):1312-20
references: 22445513
references: Exp Diabetes Res. 2012;2012:824305
references: 22899902
references: Endocrinology. 2011 Feb;152(2):394-404
references: 21159853
references: N Engl J Med. 2012 Apr 26;366(17):1577-85
references: 22449317