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Effects of GLP-1 on appetite and weight

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Abstract

Glucagon-like peptide 1 (GLP-1) is a cleavage product of the pre-proglucagon gene which is expressed in the α-cells of the pancreas, the L-cells of the intestine, and neurons located in the caudal brainstem and hypothalamus. GLP-1 is of relevance to appetite and weight maintenance because it has actions on the gastrointestinal tract as well as the direct regulation of appetite. It delays gastric emptying and gut motility in humans. In addition, interventricular injections of GLP-1 inhibit food intake, independent of the presence of food in the stomach or gastric emptying. Peripherally administered GLP-1 also affects the central regulation of feeding. It is therefore the synergistic actions of GLP-1 in the gut and brain, acting on both central and peripheral receptors that seem responsible for the effects of the hormone on satiety.

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References

  1. Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007;87:1409–39.

    Article  CAS  PubMed  Google Scholar 

  2. Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007;132(6):2131–57.

    Article  CAS  PubMed  Google Scholar 

  3. Dailey MJ et al. Disassociation between preprandial gut peptide release and food-anticipatory activity. Endocrinology. 2012;153:132–42.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Vahl TP et al. Meal-anticipatory glucagon-like peptide-1 secretion in rats. Endocrinology. 2010;151:569–75.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Tang-Christensen M, Vrang N, Larsen PJ. Glucagon-like peptide containing pathways in the regulation of feeding behaviour. Int J Obes Relat Metab Disord. 2001;25 Suppl 5:S42–7.

    Article  CAS  PubMed  Google Scholar 

  6. Elliott RM, Morgan LM, Tredger JA, Deacon S, Wright J. Glucagon-like peptide-1 (7–36) amide and glucose-dependent insulinotropic polypeptide secretion in response to nutrient ingestion in man: acute post-prandial and 24-h secretion patterns. J Endocrinol. 1993;138:159–66.

    Article  CAS  PubMed  Google Scholar 

  7. Hermann C, Goke R, Richter G, Fehmann HC, Arnold R, Goke B. Glucagon-like peptide-1 and glucose-dependent insulin-releasing polypeptide plasma levels in response to nutrients. Digestion. 1995;56:117–26.

    Article  Google Scholar 

  8. Rocca AS, Brubaker PL. Role of the vagus nerve in mediating proximal nutrient-induced glucagon- like peptide-1 secretion. Endocrinology. 1999;140(4):1687–94.

    CAS  PubMed  Google Scholar 

  9. Balks HJ, Holst JJ, Von Zur MA, Brabant G. Rapid oscillations in plasma glucagon-like peptide-1 (GLP-1) in humans: Cholinergic control of GLP-1 secretion via muscarinic receptors. J Clin Endocrinol Metab. 1997;82(3):786–90.

    CAS  PubMed  Google Scholar 

  10. Theodorakis MJ, Carlson O, Michopoulos S, et al. Human duodenal enteroendocrine cells: source of both incretin peptides, GLP-1 and GIP. Am J Physiol Endocrinol Metab. 2006;290:E550–9.

    Article  CAS  PubMed  Google Scholar 

  11. Tolhurst G, Reimann F, Gribble FM. Nutritional regulation of glucagon-like peptide-1 secretion. J Physiol. 2009;587(1):27–32.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Schjoldager B, Mortensen PE, Myhre J, Christiansen J, Holst JJ. Oxyntomodulin from distal gut: role in regulation of gastric and pancreatic functions. Dig Dis Sci. 1989;34:1411–9.

    Article  CAS  PubMed  Google Scholar 

  13. Tang-Christensen M, Larsen PJ, Thulesen J, Rømer J, Vrang N. The proglucagon-derived peptide, glucagon-like peptide-2, is a neurotransmitter involved in the regulation of food intake. Nat Med. 2000;6(7):802–7.

    Article  CAS  PubMed  Google Scholar 

  14. Lovshin J, Estall J, Yusta B, Brown TJ, Drucker DJ. Glucagon-like Peptide (GLP)-2 action in the murine central nervous system is enhanced by elimination of GLP-1 receptor signaling. J Biol Chem. 2001;276(24):21489–99.

    Article  CAS  PubMed  Google Scholar 

  15. Nauck MA, Niedereichholz U, Ettler R, et al. Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans. Am J Physiol. 1997;273:E981–8.

    CAS  PubMed  Google Scholar 

  16. Schirra J, Wank U, Arnold R, Goke B, Katschinski M. Effects of glucagon-like peptide-1 (7–36) amide on motility and sensation of the proximal stomach in humans. Gut. 2002;50:341–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Meier JJ, Gallwitz B, Salmen S, et al. Normalization of glucose concentrations and deceleration of gastric emptying after solid meals during intravenous glucagon-like peptide 1 in patients with type 2 diabetes. J Clin Endocrinol Metab. 2003;88:2719–25.

    Article  CAS  PubMed  Google Scholar 

  18. Delgado-Aros S, Doe-Young K, Burton DD, Thomforde GM, et al. Effect of GLP-1 on gastric volume, emptying, maximum volume ingested, and postprandial symptoms in humans. Am J Physiol Gastrointest Liver Physiol. 2002;282:G424–31.

    CAS  PubMed  Google Scholar 

  19. Ruttimann EB et al. Intrameal hepatic portal and intraperitoneal infusions of glucagon-like peptide-1 reduce spontaneous meal size in the rat via different mechanisms. Endocrinology. 2009;150:1174–81.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Turton MD, O’Shea D, Gunn I, et al. A role for glucagon-like peptide-1 in the central regulation of feeding. Nature. 1996;379:69–72.

    Article  CAS  PubMed  Google Scholar 

  21. Barrera JG et al. Hyperphagia and increased fat accumulation in two models of chronic CNS glucagon-like peptide-1 loss of function. J Neurosci. 2011;31:3904–13.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Chaudhri OB, Parkinson JR, Kuo YT, et al. Differential hypothalamic neuronal activation following peripheral injection of GLP-1 and oxyntomodulin in mice detected by manganese-enhanced magnetic resonance imaging. Biochem Biophys Res Commun. 2006;350:298–306.

    Article  CAS  PubMed  Google Scholar 

  23. Min DK, Tuor UI, Koopmans HS, Chelikani PK. Changes in differential functional magnetic resonance signals in the rodent brain elicited by mixed-nutrient or protein-enriched meals. Gastroenterology. 2011;141:1832–41.

    Article  CAS  PubMed  Google Scholar 

  24. Dailey M.J., Moran T. H. Glucagon-like peptide 1 and appetite. Trends in Endocrinology and Metabolism. 2013; 24 (2).

  25. Larsen PJ et al. Central administration of glucagon-like peptide-1 activates hypothalamic neuroendocrine neurons in the rat. Endocrinology. 1997;138:4445–55.

    CAS  PubMed  Google Scholar 

  26. Seo S. Acute effects of glucagon-like peptide-1 on hypothalamic neuropeptide and AMP activated kinase expression in fasted rats. Endocr J. 2008;55:867–74.

    Article  CAS  PubMed  Google Scholar 

  27. Bugarith K et al. Basomedial hypothalamic injections of neuropeptide Y conjugated to saporin selectively disrupt hypothalamic controls of food intake. Endocrinology. 2005;146:1179–91.

    Article  CAS  PubMed  Google Scholar 

  28. Blevins JE, Baskin DG. Hypothalamic-brainstem circuits controlling eating. Forum Nutr. 2010;63:133–40.

    Article  CAS  PubMed  Google Scholar 

  29. Richards P, Parker HE, Adriaenssens AE, et al. (2013) Identification and characterisation of glucagon-like peptide-1 receptor expressing cells using a new transgenic mouse model. Diabetes; Publish Ahead of Print, published online December 2, 2013.

  30. Kinzig KP et al. The diverse roles of specific GLP-1 receptors in the control of food intake and the response to visceral illness. J Neurosci. 2002;22:10470–6.

    CAS  PubMed  Google Scholar 

  31. Dailey MJ, Moran T. H. Glucagon-like peptide 1 and appetite. Trends in Endocrinology and Metabolism. 2013;24 (2).

  32. Kellum JM, Kuemmerle JF, O’Dorisio TM. Gastrointestinal hormone responses to meals before and after gastric bypass and vertical banded gastroplasty. Ann Surg. 1990;211:763–70.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Laferrère B, Teixeira JMJ. Effect of weight loss by gastric bypass surgery versus hypocaloric diet on glucose and incretin levels in patients with type 2 diabetes. J Clin Endocrinol Metab. 2008;93:2479–85.

    Article  PubMed Central  PubMed  Google Scholar 

  34. le Roux CW, Aylwin SJ, Batterham RL. Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters. Ann Surg. 2006;243:108–14.

    Article  PubMed Central  PubMed  Google Scholar 

  35. Kashyap SR, Bhatt DL, Wolski K. 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. Diabetes Care. 2013;36:2175–82.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Gagner M. Sleeve gastrectomy: an ideal choice for T2DM. Nat Rev Endocrinol. 2013;9:623.

    Article  PubMed  Google Scholar 

  37. Habegger KM, Kirchner H, Yi CX, Heppner KM, et al. GLP-1R agonism enhances adjustable gastric banding in diet-induced obese rats. Diabetes Care. 2013;62(9):3261–7.

    Article  CAS  Google Scholar 

  38. Shah M, Law JH, Micheletto F, et al. Contribution of endogenous glucagon-like peptide-1 to glucose metabolism after Roux-en-Y gastric bypass. Diabetes. 2014;63:1–10.

    Article  Google Scholar 

  39. Deane AM, Nguyen NQ, Stevens JE. Endogenous glucagon-like peptide-1 slows gastric emptying in healthy subjects, attenuating postprandial glycemia. J Clin Endocrinol Metab. 2010;95:215–21.

    Article  CAS  PubMed  Google Scholar 

  40. Nicolaus M, Brödl J, Linke R, Woerle H-J, Göke B, Schirra J. Endogenous GLP-1 regulates postprandial glycemia in humans: relative contributions of insulin, glucagon, and gastric emptying. J Clin Endocrinol Metab. 2011;96:229–36.

    Article  CAS  PubMed  Google Scholar 

  41. Wilson-Perez HE, Chambers AP, Ryan KK, Li B, Sandoval DA, et al. Vertical sleeve gastrectomy is effective in two genetic mouse models of glucagon-like peptide 1 receptor deficiency. Diabetes. 2013;62(7):2380–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Nea I. Glucagon-like peptide-1 inhibits gastric emptying via vagal afferent-mediated central mechanisms. Am J Physiol Rev. 1997;273:G920–7.

    Google Scholar 

  43. Aea W. Glucagon-like peptide-1 inhibits gastropancreatic function by inhibiting central parasympathetic outflow. Am J Physiol. 1998;275:G984–92.

    Google Scholar 

  44. Aea A. Peripheral motor action of glucagon-like peptide-1 through enteric neuronal receptors. Neurogastroenterol Motil. 2010;22:664–e203.

    Article  Google Scholar 

  45. Mea T-C. Central administration of GLP-1-(7–36) amide inhibits food and water intake in rats. Am J Physiol. 1996;271:R848–56.

    Google Scholar 

  46. Gulpinar MA. Glucagon-like peptide (GLP-1) is involved in the central modulation of fecal output in rats. Am J Physiol Gastrointest Liver Physiol. 2000;278:924–9.

    Google Scholar 

  47. Ayachi SE. Contraction induced by glicentin on smooth muscle cells from the human colon is abolished by exendin (9–39). Neurogastroenterol Motil. 2005;17:302–9.

    Article  CAS  PubMed  Google Scholar 

  48. Yoder SM. Stimulation of incretin secretion by dietary lipid: is it dose dependent? Am J Physiol Gastrointest Liver Physiol. 2009;297:299–305.

    Article  Google Scholar 

  49. Wank U, Schirra J, Arnold R, Goke B, Katschinki M. Effects of GLP-1 on proximal gastric motor and sensory function in human. Gastroenterology. 1998;114:A1190.

    Article  Google Scholar 

  50. 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 Motil. 2003;15:435–43.

    Article  CAS  PubMed  Google Scholar 

  51. Holst JJ, Toft-Nielsen MB, Orskov C, Nauck M, Willms B. On the effects of glucagon-like peptide-1 on blood glucose regulation in normal and diabetic subjects. Ann N Y Acad Sci. 1996;805:729–36.

    Article  CAS  PubMed  Google Scholar 

  52. Zander M, Madsbad S, Madsen JL, Holst JJ. Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and beta-cell function in type 2 diabetes: a arallel-group study. Lancet. 2002;359:824–30.

    Article  CAS  PubMed  Google Scholar 

  53. Vilsboll T, Christensen M, Junker AE FKK, Gluud LL. Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. BMJ. 2012;344:7771.

    Article  Google Scholar 

  54. Buse JB, Henry RR, Han J, Kim DD, MS F, Baron AD. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care. 2004;27:2628–35.

    Article  CAS  PubMed  Google Scholar 

  55. DeFronzo RA, Ratner RE, Han J, et al. Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care. 2005;28:1092–100.

    Article  CAS  PubMed  Google Scholar 

  56. Moretto TJ, Milton DR RT, Macconell LA, Okerson T, AM W, Brodows RG. Efficacy and tolerability of exenatide monotherapy over 24 weeks in antidiabetic drug-naive patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel group study. Clin Ther. 2008;30:1448–60.

    Article  CAS  PubMed  Google Scholar 

  57. Astrup A, Rossner S, Van GL, et al. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study. Lancet. 2009;374:1606–16.

    Article  CAS  PubMed  Google Scholar 

  58. Bergenstal R, Lewin A, Bailey T, Chang D, Gylvin T, Roberts V. Efficacy and safety of biphasic insulin aspart 70/30 versus exenatide in subjects with type 2 diabetes failing to achieve glycemic control with metformin and a sulfonylurea. Curr Med Res Opin. 2009;25:65–75.

    Article  CAS  PubMed  Google Scholar 

  59. Russell-Jones D, Vaag A, Schmitz O, et al. Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met + SU): a randomised controlled trial. Diabetologia. 2009;52:2046–55.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  60. Gallwitz B, Bohmer M, Segiet T, et al. Exenatide twice daily versus premixed insulin aspart 70/30 in metformin-treated patients with type 2 diabetes: a randomized 26-week study on glycemic control and hypoglycemia. Diabetes Care. 2011;34:604–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Buse JB, Rosenstock J, Sesti G, et al. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet. 2009;374(9683):39–47.

    Article  CAS  PubMed  Google Scholar 

  62. Buse JB, Nauck M, Forst T. Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a randomised, open-label study. Lancet. 2013;381:117–24.

    Article  CAS  PubMed  Google Scholar 

  63. Kelly A, Rudser KD, Nathan BM, Fox CK, et al. The effect of glucagon-like peptide-1 receptor agonist therapy on body mass index in adolescents with severe obesity. JAMA Pediatr. 2013;167(4):355–60.

    Article  PubMed Central  PubMed  Google Scholar 

  64. Bunck MC, Diamant M, Eliasson B, et al. Exenatide affects circulating cardiovascular risk biomarkers independently of changes in body composition. Diabetes Care. 2010;33:1734–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  65. Jendle J, Nauck MA, Matthews DR, Frid A, Hermansen K, et al. Weight loss with liraglutide, a once-daily human glucagon-like peptide-1 analogue for type 2 diabetes treatment as monotherapy or added to metformin, is primarily as a result of a reduction in fat tissue. Diabetes Obes Metab. 2009;11:1163–72.

    Article  CAS  PubMed  Google Scholar 

  66. Zoicas F, Droste M, Mayr B, Buchfelder M, Schofl C, et al. GLP-1 analogues as a new treatment option for hypothalamic obesity in adults: report of nine cases. Eur J Endocrinol. 2013;168(5):699–706.

    Article  CAS  PubMed  Google Scholar 

  67. Garber A, Henry RR RR, Hale P, CT C, Bode B. Liraglutide, a once-daily human glucagon-like peptide 1 analogue, provides sustained improvements in glycaemic control and weight for 2 years as monotherapy compared with glimepiride in patients with type 2 diabetes. Diabetes Obes Metab. 2011;13:348–56.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  68. Macconell L, Pencek R, Li Y, Maggs D, Porter L. Exenatide once weekly: sustained improvement in glycemic control and cardiometabolic measures through 3 years. Diabetes Metab Syndr Obes. 2013;6:31–41.

    PubMed Central  PubMed  Google Scholar 

  69. Bunck MC, Corner A, Eiasson B, et al. Effects of exenatide on measures of beta-cell function after 3years in metformin-treated patients with type 2 diabetes. Diabetes Care. 2011;34:2041–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  70. van Bloemendaal L, Ten Kulve JS, la Fleur SE, Ijzerman RG, Diamant M. Effects of GLP-1 on appetite and body weight: focus on the central nervous system. J Endocrinol. 2013 (Dec 9. [Epub ahead of print]).

  71. Butler AE, Campbell-Thompson M, Gurlo T, Dawson DW, Atkinson M, Butler PC. Marked expansion of exocrine and endocrine pancreas with incretin therapy in humans with increased exocrine pancreas dysplasia and the potential for glucagon-producing neuroendocrine tumors. Diabetes. 2013;62:2595–604.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  72. Kral JG. Vagal nerve function in obesity: therapeutic implications. World J Surg. 2009;33:1995–2006.

    Article  PubMed  Google Scholar 

  73. Hoyda TD, Smoth PM, Ferguson AV. Gastrointestinal hormone actions in the central regulation of energy metabolism: potential sensory roles for the circumventricular organs. Int J Obes. 2009;33:S16–21.

    Article  CAS  Google Scholar 

  74. Thorens B, Larsen P. Gut-derived signaling molecules and vagal afferents in the control of glucose and energy homeostasis. Curr Opin Clin Nutr Metab Care. 2004;7:471–8.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors acknowledge the support of the Mayo Clinic General Clinical Research Center (DK TR000135). Dr. Vella is supported by DK78646 and by DK82396.

Conflict of interest

Dr. Vella has received research grants from Merck and Daiichi-Sankyo. He is an investigator in multicenter studies sponsored by Novartis and GI dynamics, respectively. He has consulted for XOMA, Sanofi-Aventis, Novartis and Bristol-Myers Squibb. Dr. Shah has no relevant disclosures.

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Shah, M., Vella, A. Effects of GLP-1 on appetite and weight. Rev Endocr Metab Disord 15, 181–187 (2014). https://doi.org/10.1007/s11154-014-9289-5

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