Murray CJL, Aravkin AY, Zheng P, et al. Global burden of 87 risk factors in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396(10258):1223–49.

Article  Google Scholar 

IDF Diabetes Atlas 10th edition. International Diabetes Federation; 2021. (IDF Diabetes Atlas). Report no. 10. https://diabetesatlas.org/atlas/tenth-edition/.

Kinlen D, Cody D, O’Shea D. Complications of obesity. QJM Mon J Assoc Physicians. 2018;111(7):437–43.

Article  CAS  Google Scholar 

Lobstein T, Brinsden H, Neveux M. World Obesity Atlas 2022. Ludgate House, 107–111 Fleet Street, London, EC4A 2AB: World Obesity; 2022 May. https://www.worldobesity.org/resources/resource-library/world-obesity-atlas-2022.

Müller TD, Blüher M, Tschöp MH, DiMarchi RD. Anti-obesity drug discovery: advances and challenges. Nat Rev Drug Discov. 2022;21(3):201–23.

Article  PubMed  Google Scholar 

Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372(6505):425–32.

Article  CAS  PubMed  Google Scholar 

Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999;402(6762):656–60.

Article  CAS  PubMed  Google Scholar 

Tschöp M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature. 2000;407(6806):908–13.

Article  PubMed  Google Scholar 

Maes HH, Neale MC, Eaves LJ. Genetic and environmental factors in relative body weight and human adiposity. Behav Genet. 1997;27(4):325–51.

Article  CAS  PubMed  Google Scholar 

Locke AE, Kahali B, Berndt SI, et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015;518(7538):197–206.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yeo GSH, Farooqi IS, Aminian S, Halsall DJ, Stanhope RG, O’Rahilly S. A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nat Genet. 1998;20(2):111–2.

Article  CAS  PubMed  Google Scholar 

Farooqi IS, Jebb SA, Langmack G, et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med. 1999;341(12):879–84.

Article  CAS  PubMed  Google Scholar 

Heymsfield SB, Greenberg AS, Fujioka K, et al. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA. 1999;282(16):1568–75.

Article  CAS  PubMed  Google Scholar 

Khatib MN, Shankar AH, Kirubakaran R, et al. Ghrelin for the management of cachexia associated with cancer. Cochrane Database Syst Rev. 2018;2018(2):CD012229.

PubMed Central  Google Scholar 

Hagemann CA, Jensen MS, Holm S, et al. LEAP2 reduces postprandial glucose excursions and ad libitum food intake in healthy men. Cell Rep Med. 2022;3(4):100582.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Müller TD, Nogueiras R, Andermann ML, et al. Ghrelin. Mol Metab. 2015;4(6):437–60.

Article  PubMed  PubMed Central  Google Scholar 

Clemmensen C, Müller TD, Woods SC, Berthoud HR, Seeley RJ, Tschöp MH. Gut-brain cross-talk in metabolic control. Cell. 2017;168(5):758–74.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tschöp MH, Friedman JM. Seeking satiety: from signals to solutions. Sci Transl Med. 2023;15(723):eadh4453.

Article  PubMed  Google Scholar 

Murlin JR, Clough HD, Gibbs CBF, Stokes AM. Aqueous extracts of pancreas: I. influence on the carbohydrate metabolism of depancreatized animals. J Biol Chem. 1923;56(1):253–96.

Article  CAS  Google Scholar 

Svoboda M, Tastenoy M, Vertongen P, Robberecht P. Relative quantitative analysis of glucagon receptor mRNA in rat tissues. Mol Cell Endocrinol. 1994;105(2):131–7.

Article  CAS  PubMed  Google Scholar 

Svendsen B, Larsen O, Gabe MBN, et al. Insulin secretion depends on intra-islet glucagon signaling. Cell Rep. 2018;25(5):1127–34.e2.

Article  CAS  PubMed  Google Scholar 

Habegger KM, Heppner KM, Geary N, Bartness TJ, DiMarchi R, Tschöp MH. The metabolic actions of glucagon revisited. Nat Rev Endocrinol. 2010;6(12):689–97.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Müller TD, Finan B, Clemmensen C, DiMarchi RD, Tschöp MH. The new biology and pharmacology of glucagon. Physiol Rev. 2017;97(2):721–66.

Article  PubMed  Google Scholar 

Samols E, Marri G, Marks V. Interrelationship of glucagon, insulin and glucose: the insulinogenic effect of glucagon. Diabetes. 1966;15(12):855–66.

Article  CAS  PubMed  Google Scholar 

D’Alessio DA, Marks V. Glucagon as the first incretin: objects (in the rearview mirror) are closer than they appear. Diabetes. 2023;72(12):1739–40.

Article  PubMed  Google Scholar 

Capozzi ME, D’Alessio DA, Campbell JE. The past, present, and future physiology and pharmacology of glucagon. Cell Metab. 2022;34(11):1654–74.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Farahani RA, Egan AM, Welch AA, et al. The effect of glucagon-like peptide 1 receptor blockade on glucagon-induced stimulation of insulin secretion. Diabetes. 2023;72(4):449–54.

Article  CAS  PubMed  Google Scholar 

Brown JC, Mutt V, Pederson RA. Further purification of a polypeptide demonstrating enterogastrone activity. J Physiol. 1970;209(1):57–64.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Brown JC, Pederson RA, Jorpes E, Mutt V. Preparation of highly active enterogastrone. Can J Physiol Pharmacol. 1969;47(1):113–4.

Article  CAS  PubMed  Google Scholar 

Dupre J, Ross SA, Watson D, Brown JC. Stimulation of insulin secretion by gastric inhibitory polypeptide in man. J Clin Endocrinol Metab. 1973;37(5):826–8.

Article  CAS  PubMed  Google Scholar 

Meier JJ, Goetze O, Anstipp J, et al. Gastric inhibitory polypeptide does not inhibit gastric emptying in humans. Am J Physiol Endocrinol Metab. 2004;286(4):E621–5.

Article  CAS  PubMed  Google Scholar 

Nauck MA, Bartels E, Orskov C, Ebert R, Creutzfeldt W. Lack of effect of synthetic human gastric inhibitory polypeptide and glucagon-like peptide 1 [7-36 amide] infused at near-physiological concentrations on pentagastrin-stimulated gastric acid secretion in normal human subjects. Digestion. 1992;52(3–4):214–21.

Article  CAS  PubMed  Google Scholar 

Christensen M, Vedtofte L, Holst JJ, Vilsbøll T, Knop FK. Glucose-dependent insulinotropic polypeptide: a bifunctional glucose-dependent regulator of glucagon and insulin secretion in humans. Diabetes. 2011;60(12):3103–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kim SJ, Nian C, McIntosh CHS. Activation of lipoprotein lipase by glucose-dependent insulinotropic polypeptide in adipocytes. A role for a protein kinase B, LKB1, and AMP-activated protein kinase cascade. J Biol Chem. 2007;282(12):8557–67.

Article  CAS  PubMed  Google Scholar 

Kim SJ, Nian C, McIntosh CHS. Resistin is a key mediator of glucose-dependent insulinotropic polypeptide (GIP) stimulation of lipoprotein lipase (LPL) activity in adipocytes. J Biol Chem. 2007;282(47):34139–47.

Article  CAS  PubMed  Google Scholar 

Kim SJ, Nian C, McIntosh CHS. GIP increases human adipocyte LPL expression through CREB and TORC2-mediated trans-activation of the LPL gene. J Lipid Res. 2010;51(11):3145–57.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ebert R, Creutzfeldt W. Metabolic effects of gastric inhibitory polypeptide. In: Blazquez E, editor. Gut regulatory peptides: their role in health and disease. Berlin: S. Karger AG; 1988.

Google Scholar 

McIntosh CH, Bremsak I, Lynn FC, et al. Glucose-dependent insulinotropic polypeptide stimulation of lipolysis in differentiated 3T3-L1 cells: wortmannin-sensitive inhibition by insulin. Endocrinology. 1999;140(1):398–404.

Article  CAS  PubMed  Google Scholar 

Heimburger SMN, Nielsen CN, Calanna S, et al. Glucose-dependent insulinotropic polypeptide induces lipolysis during stable basal insulin substitution and hyperglycaemia in men with type 1 diabetes: a randomized, double-blind, placebo-controlled, crossover clinical trial. Diabetes Obes Metab. 2022;24(1):142–7.

Article  CAS  PubMed  Google Scholar