1. McMichael HB, Webb J, Dawson AM. The absorption of maltose and lactose in man.Clin Sci1967;33:135–145. [PubMed] [Google Scholar]
**2. Steinert RE, Feinle-Bisset C, Asarian L, et al. Ghrelin, CCK, GLP-1, and PYY(3–36): secretory controls and physiological roles in eating and glycemia in health, obesity, and after RYGB.Physiol Rev2017;97:411–463. [PMC free article] [PubMed] [Google Scholar]
Encyclopedic review of the 4 hormones or incretins and their roles and mechanisms of action in control of appetite and glycemia.
*3. Vella A, Camilleri M. The gastrointestinal tract as an integrator of mechanical and hormonal response to nutrient ingestion.Diabetes2017;66:2729–2737. [PMC free article] [PubMed] [Google Scholar]
Overview of the role of the gastrointestinal tract in satiation and the diverse incretin and hormonal responses to nutrien ingestion.
*4. Camilleri M, Acosta A. Combination therapies for obesity.Metab Syndr Relat Disord2018. July11. doi: 10.1089/met.2018.0075. [Epub ahead of print] [PMC free article] [PubMed] [CrossRef] [Google Scholar]
Overview of the combination pharmacological, device and surgical treatments and their impact on incretin or hormonal mechanisms to induce weight loss.
5. Camilleri MClinical practice. Diabetic gastroparesis.N Engl J Med2007;356:820–829. [PubMed] [Google Scholar]
6. Camilleri MIntegrated upper gastrointestinal response to food intake.Gastroenterology2006;131:640–658. [PubMed] [Google Scholar]
7. Hunt JN, Macdonald I. The influence of volume on gastric emptying.J Physiol1954;126:459–474. [PMC free article] [PubMed] [Google Scholar]
8. Heddle R, Dent J, Read NW, et al. Antropyloroduodenal motor responses to intraduodenal lipid infusion in healthy volunteers.Am J Physiol1988;254:G671–G679. [PubMed] [Google Scholar]
9. Schmidt WE, Schmitz F. Genetic dissection of the secretory machinery in the stomach.Gastroenterology2004;126:606–609. [PubMed] [Google Scholar]
10. Goetze O, Treier R, Fox M, et al. The effect of gastric secretion on gastric physiology and emptying in the fasted and fed state assessed by magnetic resonance imaging.Neurogastroenterol Motil2009;21:725–e42. [PubMed] [Google Scholar]
11. Kalkan Ç, Soykan I, Soydal Ç, et al. Assessment of gastric emptying in patients with autoimmune gastritis.Dig Dis Sci2016;61:1597–1602. [PubMed] [Google Scholar]
12. Tosetti C, Stanghellini V, Tucci A, et al. Gastric emptying and dyspeptic symptoms in patients with nonautoimmune fundic atrophic gastritis.Dig Dis Sci2000;45:252–257. [PubMed] [Google Scholar]
13. Malagelada JR. Pathophysiological responses to meals in the Zollinger–Ellison syndrome: gastric emptying and its effect on duodenal function.Gut1980;21:98–104. [PMC free article] [PubMed] [Google Scholar]
14. Scarpignato C, Micali B, Vitulo F, et al. Inhibition of gastric emptying by bombesin in man.Digestion1982;23:128–131. [PubMed] [Google Scholar]
15. Degen LP, Peng F, Collet A, et al. Blockade of GRP receptors inhibits gastric emptying and gallbladder contraction but accelerates small intestinal transit.Gastroenterology2001;120:361–368. [PubMed] [Google Scholar]
16. Beglinger C, Degen L. Fat in the intestine as a regulator of appetite--role of CCK.Physiol Behav2004;83:617–621. [PubMed] [Google Scholar]
17. Dockray GJ. Cholecystokinin.Curr Opin Endocrinol Diabetes Obes2012;19:8–12. [PubMed] [Google Scholar]
18. Lal S, McLaughlin J, Barlow J, et al. Cholecystokinin pathways modulate sensations induced by gastric distension in humans.Am J Physiol Gastrointest Liver Physiol2004;287:G72–G79. [PubMed] [Google Scholar]
19. Meyer BM, Werth BA, Beglinger C, et al. Role of cholecystokinin in regulation of gastrointestinal motor functions.Lancet1989;2(8653):12–15. [PubMed] [Google Scholar]
20. Friedenberg FK, Desipio J, Korimilli A, et al. Tonic and phasic pyloric activity in response to CCK-octapeptide.Dig Dis Sci2008;53:905–911. [PubMed] [Google Scholar]
21. Feltrin KL, Little TJ, Meyer JH, et al. Comparative effects of intraduodenal infusions of lauric and oleic acids on antropyloroduodenal motility, plasma cholecystokinin and peptide YY, appetite, and energy intake in healthy men.Am J Clin Nutr2008;87:1181–1187. [PubMed] [Google Scholar]
22. Hansotia T, Maida A, Flock G, et al. Extrapancreatic incretin receptors modulate glucose homeostasis, body weight, and energy expenditure.J Clin Invest2007;117:143–152. [PMC free article] [PubMed] [Google Scholar]
23. Sparre-Ulrich AH, Gabe MN, Gasbjerg LS, et al. GIP(3–30)NH2 is a potent competitive antagonist of the GIP receptor and effectively inhibits GIP-mediated insulin, glucagon, and somatostatin release.Biochem Pharmacol2017;131:78–88. [PubMed] [Google Scholar]
*24. Asmar M, Asmar A, Simonsen L, et al. The gluco- and liporegulatory and vasodilatory effects of glucose-dependent insulinotropic polypeptide (GIP) are abolished by an antagonist of the human GIP receptor.Diabetes2017;66:2363–2371. [PubMed] [Google Scholar]
Proof of concept on a new class of antagonist directed to GIP receptor, which is a totally novel target with potential for glycemic control and postentially for obesity
25. Gasbjerg LS, Gabe MBN, Hartmann B, et al. Glucose-dependent insulinotropic polypeptide (GIP) receptor antagonists as anti-diabetic agents.Peptides2018;100:173–181. [PubMed] [Google Scholar]
**26. Gasbjerg LS, Christensen MB, Hartmann B, et al. GIP(3–30)NH2 is an efficacious GIP receptor antagonist in humans: a randomised, double-blinded, placebo-controlled, crossover study.Diabetologia2018;61:413–423. [PubMed] [Google Scholar]
Proof of efficacy from RCT that a GIP receptor antagonist is effective in control of glycemia
27. Delgado-Aros S, Kim DY, Burton DD, et al. Effect of GLP-1 on gastric volume, emptying, maximum volume ingested, and postprandial symptoms in humans.Am J Physiol Gastrointest Liver Physiol2002;282:G424–G431. [PubMed] [Google Scholar]
28. Delgado-Aros S, Vella A, Camilleri M, et al. Effects of glucagon-like peptide-1 and feeding on gastric volumes in diabetes mellitus with cardio-vagal dysfunction.Neurogastroenterol Motil2003;15:435–443. [PubMed] [Google Scholar]
29. Schirra J, Nicolaus M, Woerle HJ, et al. GLP-1 regulates gastroduodenal motility involving cholinergic pathways.Neurogastroenterol Motil2009;21:609–618, e621–602. [PubMed] [Google Scholar]
30. Vazquez-Roque MI, Camilleri M, Vella A, et al. Association of TCF7L2 allelic variations with gastric function, satiation, and GLP-1 levels.Clin Transl Sci2011;4:183–187. [PMC free article] [PubMed] [Google Scholar]
31. Schirra J, Nicolaus M, Roggel R, et al. Endogenous glucagon-like peptide 1 controls endocrine pancreatic secretion and antro-pyloro-duodenal motility in humans.Gut2006;55:243–251. [PMC free article] [PubMed] [Google Scholar]
32. Halim MA, Degerblad M, Sundbom M, et al. Glucagon-like peptide-1 inhibits prandial gastrointestinal motility through myenteric neuronal mechanisms in humans.J Clin Endocrinol Metab2018;103:575–585. [PubMed] [Google Scholar]
33. Iwasaki Y, Goswami C, Yada T. Glucagon-like peptide-1 and insulin synergistically activate vagal afferent neurons.Neuropeptides2017;65:77–82. [PubMed] [Google Scholar]
34. Kobashi M, Mizutani S, Fujita M, et al. Central glucagon like peptide-1 inhibits reflex swallowing elicited by the superior laryngeal nerve via caudal brainstem in the rat.Brain Res2017;1671:26–32 [PubMed] [Google Scholar]
**35. Grasset E, Puel A, Charpentier J, et al. A specific gut microbiota dysbiosis of type 2 diabetic mice induces GLP-1 resistance through an enteric NO-dependent and gut-brain axis mechanism.Cell Metab2017;26:278. [PubMed] [Google Scholar]
Extremely interesting and provocative study showing that gut microbiota are required for the effects of GLP-1 on the inhibition of gastrointestinal motor functions; this ushers the discussion of the potential role of microbiota and the interaction of high fat diet with resistance to the effects of GLP1, possibly through alterations of the microbiota.
36. Deane AM, Nguyen NQ, Stevens JE, et al. Endogenous glucagon-like peptide-1 slows gastric emptying in healthy subjects, attenuating postprandial glycemia.J Clin Endocrinol Metab2010;95:215–221. [PubMed] [Google Scholar]
37. Acosta A, Camilleri M, Burton D, et al. Exenatide in obesity with accelerated gastric emptying: a randomized, pharmacodynamics study.Physiol Rep2015;3(11).pii:e12610. [PMC free article] [PubMed] [Google Scholar]
38. Halawi H, Khemani D, Eckert D, et al. Effects of liraglutide on weight, satiation, and gastric functions in obesity: a randomised, placebo-controlled pilot trial.Lancet Gastroenterol Hepatol2017;2:890–899. [PubMed] [Google Scholar]
Randomized controlled tiral demonstrating relationship between retardation of gastric emptying and weight loss in response to GLP-1 analog, liraglutide
39. Hjerpsted JB, Flint A, Brooks A, et al. Semaglutide improves postprandial glucose and lipid metabolism, and delays first-hour gastric emptying in subjects with obesity.Diabetes Obes Metab2018;20:610–619. [PMC free article] [PubMed] [Google Scholar]
40. Shah M, Law JH, Micheletto F, et al. Contribution of endogenous glucagon-like peptide 1 to glucose metabolism after Roux-en-Y gastric bypass.Diabetes2014;63:483–493. [PMC free article] [PubMed] [Google Scholar]
41. Nagell CF, Wettergren A, Pedersen JF, et al. Glucagon-like peptide-2 inhibits antral emptying in man, but is not as potent as glucagon-like peptide-1.Scand J Gastroenterol2004;39:353–358. [PubMed] [Google Scholar]
42. Berg JK, Kim EH, Li B, et al. A randomized, double-blind, placebo-controlled, multiple-dose, parallel-group clinical trial to assess the effects of teduglutide on gastric emptying of liquids in healthy subjects.BMC Gastroenterol2014;14:25. [PMC free article] [PubMed] [Google Scholar]
43. Iturrino J, Camilleri M, Acosta A, et al. Acute effects of a glucagon-like peptide 2 analogue, teduglutide, on gastrointestinal motor function and permeability in adult patients with short bowel syndrome on home parenteral nutrition.J Parenter Enteral Nutr2016;40:1089–1095. [PubMed] [Google Scholar]
44. Meier JJ, Nauck MA, Pott A, et al. Glucagon-like peptide 2 stimulates glucagon secretion, enhances lipid absorption, and inhibits gastric acid secretion in humans.Gastroenterology2006;130:44–54. [PubMed] [Google Scholar]
45. Wismann P, Pedersen SL, Hansen G, et al. Novel GLP-1/GLP-2 co-agonists display marked effects on gut volume and improves glycemic control in mice.Physiol Behav2018;192:72–81. [PubMed] [Google Scholar]
46. Tschöp MH. article in this issue - Ghrelin and Gastrointestinal Motility Disorders
47. Murray CD, Martin NM, Patterson M, et al. Ghrelin enhances gastric emptying in diabetic gastroparesis: a double blind, placebo controlled, crossover study.Gut2005;54:1693–1698. [PMC free article] [PubMed] [Google Scholar]
48. Cremonini F, Camilleri M, Vazquez Roque M, et al. Obesity does not increase effects of synthetic ghrelin on human gastric motor functions.Gastroenterology2006;131:1431–1439. [PubMed] [Google Scholar]
49. Shin A, Camilleri M, Busciglio I, et al. Randomized controlled phase Ib study of ghrelin agonist, RM-131, in type 2 diabetic women with delayed gastric emptying: pharmaco*kinetics and pharmacodynamics.Diabetes Care2013;36:41–48. [PMC free article] [PubMed] [Google Scholar]
50. Shin A, Camilleri M, Busciglio I, et al. Ghrelin agonist RM-131 accelerates gastric emptying of solids and reduces symptoms in patients with type 1 diabetes mellitus.Clin Gastroenterol Hepatol2013;11:1453–1459. [PMC free article] [PubMed] [Google Scholar]
51. Nelson A, Camilleri M, Acosta A, et al. Effects of ghrelin receptor agonist, relamorelin, on gastric motor functions and satiation in healthy volunteers.Neurogastroenterol Motil2016;28:1705–1713. [PMC free article] [PubMed] [Google Scholar]
52. Lembo A, Camilleri M, McCallum R, et al. Relamorelin reduces vomiting frequency and severity and improves gastric emptying in adults with diabetic gastroparesis.Gastroenterology2016;151:87–96, e6. [PubMed] [Google Scholar]
*53. Camilleri M, McCallum RW, Tack J, et al. Efficacy and safety of relamorelin in diabetes with symptoms of gastroparesis: a randomized, placebo-controlled study.Gastroenterology2017;153:1240–1250, e2. [PMC free article] [PubMed] [Google Scholar]
Randomized controlled trial demonstrating efficacy of pentapeptide ghrelin agonist, relamorelin, on gastric emptying and symptoms of gastroparesis in diabetics
54. Cinti S, de Matteis R, Ceresi E, et al. Leptin in the human stomach.Gut2001;49:155–159. [PMC free article] [PubMed] [Google Scholar]
55. Cammisotto PG, Renaud C, Gingras D, et al. Endocrine and exocrine secretion of leptin by the gastric mucosa.J Histochem Cytochem2005;53:851–860. [PubMed] [Google Scholar]
56. Barrenetxe J, Villaro AC, Guembe L, et al. Distribution of the long leptin receptor isoform in brush border, basolateral membrane, and cytoplasm of enterocytes.Gut2008;50:797–809. [PMC free article] [PubMed] [Google Scholar]
57. Asakawa A, Inui A, Ueno N, et al. Urocortin reduces food intake and gastric emptying in lean and ob/ob obese mice.Gastroenterology1999;116:1287. [PubMed] [Google Scholar]
58. Hayashi Y, Toyomasu Y, Saravanaperumal SA, et al. Hyperglycemia increases interstitial cells of Cajal via MAPK1 and MAPK3 signaling to ETV1 and KIT, leading to rapid gastric emptying.Gastroenterology2017;153:521–535. [PMC free article] [PubMed] [Google Scholar]
59. Kamegai J, Tamura H, Shimizu T, et al. Effects of insulin, leptin, and glucagon on ghrelin secretion from isolated perfused rat stomach.Regul Pept2004;119:77–81. [PubMed] [Google Scholar]
60. Zhao Z, Sakai T. Characteristic features of ghrelin cells in the gastrointestinal tract and the regulation of stomach ghrelin expression and production.World J Gastroenterol2008;14:6306–6311. [PMC free article] [PubMed] [Google Scholar]
61. Charron MJ, Vuguin PM. Lack of glucagon receptor signaling and its implications beyond glucose homeostasis.J Endocrinol2015;224:R123–R130. [PubMed] [Google Scholar]
62. Heppner KM, Habegger KM, Day J, et al. Glucagon regulation of energy metabolism.Physiol Behavior2010;100:545–548. [PubMed] [Google Scholar]
63. Patel GK, Whalen GE, Soergel KH, et al. Glucagon effects on the human small intestine.Dig Dis Sci1979;24:501–508. [PubMed] [Google Scholar]
64. Samsom M, Szarka LA, Camilleri M, et al. Pramlintide, an amylin analog, selectively delays gastric emptying: potential role of vagal inhibition.Am J Physiol Gastrointest Liver Physiol2000;278:G946–951. [PubMed] [Google Scholar]
65. Vella A, Lee JS, Camilleri M, et al. Effects of pramlintide, an amylin analogue, on gastric emptying in type 1 and 2 diabetes mellitus.Neurogastroenterol Motil2002;14:123–131. [PubMed] [Google Scholar]
66. Hinshaw L, Schiavon M, Mallad A, et al. Effects of delayed gastric emptying on postprandial glucose kinetics, insulin sensitivity, and β-cell function.Am J Physiol Endocrinol Metab2014;307:E494–E502. [PMC free article] [PubMed] [Google Scholar]
67. Ballantyne GH. Peptide YY(1–36) and peptide YY(3–36): Part 1. Distribution, release, and actions.Obes Surg2006;16:651–658. [PubMed] [Google Scholar]
68. Savage AP, Adrian TE, Carolan G, et al. Effects of peptide YY (PYY) on mouth to caecum intestinal transit time and on the rate of gastric emptying in healthy volunteers.Gut1987;28:166–170. [PMC free article] [PubMed] [Google Scholar]
69. Pappas TN, Debas HT, Taylor IL. Enterogastrone-like effect of peptide YY is vagally mediated in the dog.J Clin Invest1986;77:49–53. [PMC free article] [PubMed] [Google Scholar]
70. Putnam WS, Liddle RA, Williams JA. Inhibitory regulation of rat exocrine pancreas by peptide YY and pancreatic polypeptide.Am J Physiol1989;256:G698–G703. [PubMed] [Google Scholar]
71. Gantz I, Erondu N, Mallick M, et al. Efficacy and safety of intranasal peptide YY3–36 for weight reduction in obese adults.J Clin Endocrinol Metab2007;92:1754–1757. [PubMed] [Google Scholar]
72. Pironi L, Stanghellini V, Miglioli M, et al. Fat-induced ileal brake in humans: a dose-dependent phenomenon correlated to the plasma levels of peptide YY.Gastroenterology1993;105:733–739. [PubMed] [Google Scholar]
73. Schjoldager B, Mortensen PE, Myhre J, et al. Oxyntomodulin from distal gut. Role in regulation of gastric and pancreatic functions.Dig Dis Sci1989;34:1411–1419. [PubMed] [Google Scholar]
74. Bagger JI, Holst JJ, Hartmann B, et al. Effect of oxyntomodulin, glucagon, GLP-1, and combined glucagon +GLP-1 infusion on food intake, appetite, and resting energy expenditure.J Clin Endocrinol Metab2015;100:4541–4552. [PubMed] [Google Scholar]
75. Nguyen NT, Nguyen B, Gebhart A, Hohmann S. Changes in the makeup of bariatric surgery: a national increase in use of laparoscopic sleeve gastrectomy.J Am Coll Surg2013;216:252–257. [PubMed] [Google Scholar]
76. Yousseif A, Emmanuel J, Karra E, et al. Differential effects of laparoscopic sleeve gastrectomy and laparoscopic gastric bypass on appetite, circulating acyl-ghrelin, peptide YY3–36 and active GLP-1 levels in non-diabetic humans.Obes Surg2014;24:24–52. [PMC free article] [PubMed] [Google Scholar]
77. Kashyap SR, Bhatt DL, Wolski K, et al. Metabolic effects of bariatric surgery in patients with moderate obesity and type 2 diabetes: analysis of a randomized control trial comparing surgery with intensive medical treatment.Diab Care2013;36:2175–2182. [PMC free article] [PubMed] [Google Scholar]
78. Peterli R, Steinert RE, Woelnerhanssen B, et al. Metabolic and hormonal changes after laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy: a randomized, prospective trial.Obes Surg2012;22:740–748. [PMC free article] [PubMed] [Google Scholar]
79. Peterli R, Wolnerhanssen B, Peters T, et al. Improvement in glucose metabolism after bariatric surgery: comparison of laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy: a prospective randomized trial.Ann Surg2009;250:234–241. [PubMed] [Google Scholar]
80. Lee W-J, Chong K, Ser K-H, et al. Gastric bypass vs sleeve gastrectomy for type 2 diabetes mellitus: a randomized controlled trial.Arch Surg2011;146:143–148. [PubMed] [Google Scholar]
81. Sista F, Abruzzese V, Clementi M, et al. The effect of sleeve gastrectomy on GLP-1 secrtion and gastric emptying: a prospective study.Surg Obes Relat Dis2017;13:7–14. [PubMed] [Google Scholar]
82. Hutch CR, Sandoval D. The role of GLP-1 in the metabolic success of bariatric surgery.Endocrinology2017;158:4139–4151. [PMC free article] [PubMed] [Google Scholar]
83. Magouliotis DE, Tasiopoulou VS, Sioka E, et al. Impact of bariatric surgery on metabolic and gut microbiota profile: a systematic review and meta-analysis.Obes Surg2017;27:1345–1357. [PubMed] [Google Scholar]
Summary of the effects of bariatric surgery on metabolic and hormonal responses
84. Abu Dayyeh BK, Acosta A, Camilleri M, et al. Endoscopic sleeve gastroplasty alters gastric physiology and induces loss of body weight in obese individuals.Clin Gastroenterol Hepatol2017;15:37–43,e1. [PubMed] [Google Scholar]
85. Skow MA, Bergmann NC, Knop FK. Diabetes and obesity treatment based on dual incretin receptor activation: ‘twincretins’.Diabetes Obes Metab2016;18:847–854. [PubMed] [Google Scholar]
