1.Moore, B. On the treatment of diabetus mellitus by acid extract of duodenal mucous membrane. Biochem. J. 1, 28–38 (1906).CAS
PubMed
PubMed Central
Article
Google Scholar
2.Holst, J. J. The physiology of glucagon-like peptide 1. Physiol. Rev. 87, 1409–1439 (2007).CAS
PubMed
PubMed Central
Article
Google Scholar
3.Thorens, B. Expression cloning of the pancreatic beta cell receptor for the gluco-incretin hormone glucagon-like peptide 1. Proc. Natl. Acad. Sci. USA 89, 8641–8645 (1992).CAS
PubMed
Article
PubMed Central
Google Scholar
4.Nauck, M. A. et al. Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 36, 741–744 (1993).CAS
PubMed
Article
PubMed Central
Google Scholar
5.Gribble, F. M. & Reimann, F. Function and mechanisms of enteroendocrine cells and gut hormones in metabolism. Nat. Rev. Endocrinol. 15, 226–237 (2019).CAS
PubMed
Article
PubMed Central
Google Scholar
6.Sjölund, K., Sandén, G., Håkanson, R. & Sundler, F. Endocrine cells in human intestine: an immunocytochemical study. Gastroenterology 85, 1120–1130 (1983).PubMed
Article
PubMed Central
Google Scholar
7.Lewis, J. E. et al. Selective stimulation of colonic L cells improves metabolic outcomes in mice. Diabetologia 63, 1396–1407 (2020).CAS
PubMed
PubMed Central
Article
Google Scholar
8.Batterham, R. L. et al. Inhibition of food intake in obese subjects by peptide YY3-36. N. Engl. J. Med. 349, 941–948 (2003).CAS
PubMed
Article
PubMed Central
Google Scholar
9.Gribble, F. M. & Reimann, F. Enteroendocrine cells: chemosensors in the intestinal epithelium. Annu. Rev. Physiol. 78, 277–299 (2016).CAS
PubMed
Article
PubMed Central
Google Scholar
10.Brubaker, P. L., Schloos, J. & Drucker, D. J. Regulation of glucagon-like peptide-1 synthesis and secretion in the GLUTag enteroendocrine cell line. Endocrinology 139, 4108–4114 (1998).CAS
PubMed
Article
PubMed Central
Google Scholar
11.Edfalk, S., Steneberg, P. & Edlund, H. Gpr40 is expressed in enteroendocrine cells and mediates free fatty acid stimulation of incretin secretion. Diabetes 57, 2280–2287 (2008).CAS
PubMed
PubMed Central
Article
Google Scholar
12.Chu, Z. L. et al. A role for intestinal endocrine cell-expressed G protein-coupled receptor 119 in glycemic control by enhancing glucagon-like peptide-1 and glucose-dependent insulinotropic peptide release. Endocrinology 149, 2038–2047 (2008).CAS
PubMed
Article
PubMed Central
Google Scholar
13.Hansen, K. B. et al. 2-Oleoyl glycerol is a GPR119 agonist and signals GLP-1 release in humans. J. Clin. Endocrinol. Metab. 96, E1409–E1417 (2011).CAS
PubMed
Article
PubMed Central
Google Scholar
14.Mace, O. J., Schindler, M. & Patel, S. The regulation of K- and L-cell activity by GLUT2 and CasR in rat small intestine. J. Physiol. 590, 2917–2936 (2012).CAS
PubMed
PubMed Central
Article
Google Scholar
15.Thomas, C. et al. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab 10, 167–177 (2009).CAS
PubMed
PubMed Central
Article
Google Scholar
16.Bolognini, D., Tobin, A. B., Milligan, G. & Moss, C. E. The pharmacology and function of receptors for short-chain fatty acids. Mol. Pharmacol. 89, 388–398 (2016).CAS
PubMed
Article
PubMed Central
Google Scholar
17.Pais, R., Rievaj, J., Larraufie, P., Gribble, F. & Reimann, F. Angiotensin II type 1 receptor-dependent GLP-1 and PYY secretion in mice and humans. Endocrinology 157, 3821–3831 (2016).CAS
PubMed
PubMed Central
Article
Google Scholar
18.Pais, R. et al. Role of enteroendocrine L-cells in arginine vasopressin-mediated inhibition of colonic anion secretion. J. Physiol. (Lond.) 594, 4865–4878 (2016).CAS
Article
Google Scholar
19.Psichas, A., Glass, L. L., Sharp, S. J., Reimann, F. & Gribble, F. M. Galanin inhibits GLP-1 and GIP secretion via the GAL1 receptor in enteroendocrine L and K cells. Br. J. Pharmacol. 173, 888–898 (2016).CAS
PubMed
PubMed Central
Article
Google Scholar
20.Roberge, J. N., Gronau, K. A. & Brubaker, P. L. Gastrin-releasing peptide is a novel mediator of proximal nutrient-induced proglucagon-derived peptide secretion from the distal gut. Endocrinology 137, 2383–2388 (1996).CAS
PubMed
Article
PubMed Central
Google Scholar
21.Jang, H. J. et al. Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc. Natl Acad. Sci. USA 104, 15069–15074 (2007).CAS
PubMed
Article
PubMed Central
Google Scholar
22.Saltiel, M. Y. et al. Sweet taste receptor activation in the gut is of limited importance for glucose-stimulated GLP-1 and GIP secretion. Nutrients 9, E418 (2017).PubMed
Article
CAS
PubMed Central
Google Scholar
23.Reimann, F. et al. Glucose sensing in L cells: a primary cell study. Cell Metab. 8, 532–539 (2008).CAS
PubMed
PubMed Central
Article
Google Scholar
24.Gribble, F. M., Williams, L., Simpson, A. K. & Reimann, F. A novel glucose-sensing mechanism contributing to glucagon-like peptide-1 secretion from the GLUTag cell line. Diabetes 52, 1147–1154 (2003).CAS
PubMed
Article
PubMed Central
Google Scholar
25.Gorboulev, V. et al. Na+-D-glucose cotransporter SGLT1 is pivotal for intestinal glucose absorption and glucose-dependent incretin secretion. Diabetes 61, 187–196 (2012).CAS
PubMed
Article
PubMed Central
Google Scholar
26.Reimann, F., Williams, L., da Silva Xavier, G., Rutter, G. A. & Gribble, F. M. Glutamine potently stimulates glucagon-like peptide-1 secretion from GLUTag cells. Diabetologia 47, 1592–1601 (2004).CAS
PubMed
Article
PubMed Central
Google Scholar
27.Matsumura, K., Miki, T., Jhomori, T., Gonoi, T. & Seino, S. Possible role of PEPT1 in gastrointestinal hormone secretion. Biochem. Biophys. Res. Commun. 336, 1028–1032 (2005).CAS
PubMed
Article
PubMed Central
Google Scholar
28.Diakogiannaki, E. et al. Oligopeptides stimulate glucagon-like peptide-1 secretion in mice through proton-coupled uptake and the calcium-sensing receptor. Diabetologia 56, 2688–2696 (2013).CAS
PubMed
PubMed Central
Article
Google Scholar
29.Parker, H. E. et al. Predominant role of active versus facilitative glucose transport for glucagon-like peptide-1 secretion. Diabetologia 55, 2445–2455 (2012).CAS
PubMed
PubMed Central
Article
Google Scholar
30.Powell, D. R. et al. LX4211 increases serum glucagon-like peptide 1 and peptide YY levels by reducing sodium/glucose cotransporter 1 (SGLT1)-mediated absorption of intestinal glucose. J. Pharmacol. Exp. Ther. 345, 250–259 (2013).CAS
PubMed
Article
PubMed Central
Google Scholar
31.Christiansen, C. B. et al. The impact of short-chain fatty acids on GLP-1 and PYY secretion from the isolated perfused rat colon. Am. J. Physiol. Gastrointest. Liver Physiol. 315, G53–G65 (2018).CAS
PubMed
Article
PubMed Central
Google Scholar
32.Jørgensen, N. B. et al. Acute and long-term effects of Roux-en-Y gastric bypass on glucose metabolism in subjects with type 2 diabetes and normal glucose tolerance. Am. J. Physiol. Endocrinol. Metab. 303, E122–E131 (2012).PubMed
Article
CAS
PubMed Central
Google Scholar
33.Martinussen, C. et al. The effect of acute dual SGLT1/SGLT2 inhibition on incretin release and glucose metabolism after gastric bypass surgery. Am. J. Physiol. Endocrinol. Metab. 318, E956–E964 (2020).CAS
PubMed
Article
PubMed Central
Google Scholar
34.El-Ouaghlidi, A. et al. The dipeptidyl peptidase 4 inhibitor vildagliptin does not accentuate glibenclamide-induced hypoglycemia but reduces glucose-induced glucagon-like peptide 1 and gastric inhibitory polypeptide secretion. J. Clin. Endocrinol. Metab. 92, 4165–4171 (2007).CAS
PubMed
Article
PubMed Central
Google Scholar
35.Reimann, F., Tolhurst, G. & Gribble, F. M. G-protein-coupled receptors in intestinal chemosensation. Cell Metab. 15, 421–431 (2012).CAS
PubMed
Article
PubMed Central
Google Scholar
36.Goldspink, D. A. et al. Mechanistic insights into the detection of free fatty and bile acids by ileal glucagon-like peptide-1 secreting cells. Mol. Metab. 7, 90–101 (2018).CAS
PubMed
Article
PubMed Central
Google Scholar
37.Goldspink, D. A. et al. Labeling and characterization of human GLP-1-secreting L-cells in primary ileal organoid culture. Cell Rep. 31, 107833 (2020).CAS
PubMed
PubMed Central
Article
Google Scholar
38.Brighton, C. A. et al. Bile acids trigger GLP-1 release predominantly by accessing basolaterally located G protein-coupled bile acid receptors. Endocrinology 156, 3961–3970 (2015).CAS
PubMed
PubMed Central
Article
Google Scholar
39.Christensen, L. W., Kuhre, R. E., Janus, C., Svendsen, B. & Holst, J. J. Vascular, but not luminal, activation of FFAR1 (GPR40) stimulates GLP-1 secretion from isolated perfused rat small intestine. Physiol. Rep. 3, e12551 (2015).PubMed
PubMed Central
Article
CAS
Google Scholar
40.Modvig, I. M., Kuhre, R. E. & Holst, J. J. Peptone-mediated glucagon-like peptide-1 secretion depends on intestinal absorption and activation of basolaterally located calcium-sensing receptors. Physiol. Rep. 7, e14056 (2019).PubMed
PubMed Central
Article
CAS
Google Scholar
41.Llewellyn-Smith, I. J., Reimann, F., Gribble, F. M. & Trapp, S. Preproglucagon neurons project widely to autonomic control areas in the mouse brain. Neuroscience 180, 111–121 (2011).CAS
PubMed
PubMed Central
Article
Google Scholar
42.Orskov, C., Holst, J. J., Poulsen, S. S. & Kirkegaard, P. Pancreatic and intestinal processing of proglucagon in man. Diabetologia 30, 874–881 (1987).CAS
PubMed
PubMed Central
Google Scholar
43.Rouillé, Y. et al. Proteolytic processing mechanisms in the biosynthesis of neuroendocrine peptides: the subtilisin-like proprotein convertases. Front. Neuroendocrinol. 16, 322–361 (1995).PubMed
Article
PubMed Central
Google Scholar
44.Larraufie, P. et al. Important role of the GLP-1 axis for glucose homeostasis after bariatric surgery. Cell Rep. 26, 1399–1408.e6 (2019).CAS
PubMed
PubMed Central
Article
Google Scholar
45.Song, Y. et al. Gut-proglucagon-derived peptides are essential for regulating glucose homeostasis in mice. Cell Metab. 30, 976–986.e3 (2019).CAS
PubMed
Article
PubMed Central
Google Scholar
46.Ban, K. et al. Cardioprotective and vasodilatory actions of glucagon-like peptide 1 receptor are mediated through both glucagon-like peptide 1 receptor-dependent and -independent pathways. Circulation 117, 2340–2350 (2008).CAS
PubMed
Article
PubMed Central
Google Scholar
47.Richards, P. et al. Identification and characterization of GLP-1 receptor-expressing cells using a new transgenic mouse model. Diabetes 63, 1224–1233 (2014).CAS
PubMed
Article
PubMed Central
Google Scholar
48.Pyke, C. et al. GLP-1 receptor localization in monkey and human tissue: novel distribution revealed with extensively validated monoclonal antibody. Endocrinology 155, 1280–1290 (2014).PubMed
Article
CAS
PubMed Central
Google Scholar
49.He, S. et al. Gut intraepithelial T cells calibrate metabolism and accelerate cardiovascular disease. Nature 566, 115–119 (2019).CAS
PubMed
PubMed Central
Article
Google Scholar
50.Baggio, L. L. et al. GLP-1 receptor expression within the human heart. Endocrinology 159, 1570–1584 (2018).CAS
PubMed
PubMed Central
Article
Google Scholar
51.Dhir, G. & Cusi, K. Glucagon like peptide-1 receptor agonists for the management of obesity and non-alcoholic fatty liver disease: a novel therapeutic option. J. Investig. Med. 66, 7–10 (2018).PubMed
Article
PubMed Central
Google Scholar
52.Gromada, J., Holst, J. J. & Rorsman, P. Cellular regulation of islet hormone secretion by the incretin hormone glucagon-like peptide 1. Pflugers Arch. 435, 583–594 (1998).CAS
PubMed
Article
PubMed Central
Google Scholar
53.Creutzfeldt, W. The [pre-] history of the incretin concept. Regul. Pept. 128, 87–91 (2005).CAS
PubMed
Article
PubMed Central
Google Scholar
54.Nauck, M. A., Bartels, E., Orskov, C., Ebert, R. & Creutzfeldt, W. Additive insulinotropic effects of exogenous synthetic human gastric inhibitory polypeptide and glucagon-like peptide-1-(7-36) amide infused at near-physiological insulinotropic hormone and glucose concentrations. J. Clin. Endocrinol. Metab. 76, 912–917 (1993).CAS
PubMed
PubMed Central
Google Scholar
55.Gasbjerg, L. S. et al. Separate and combined glucometabolic effects of endogenous glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 in healthy individuals. Diabetes 68, 906–917 (2019).CAS
PubMed
Article
PubMed Central
Google Scholar
56.Jørgensen, N. B. et al. Exaggerated glucagon-like peptide 1 response is important for improved β-cell function and glucose tolerance after Roux-en-Y gastric bypass in patients with type 2 diabetes. Diabetes 62, 3044–3052 (2013).PubMed
PubMed Central
Article
CAS
Google Scholar
57.Hansen, L., Deacon, C. F., Orskov, C. & Holst, J. J. Glucagon-like peptide-1-(7-36)amide is transformed to glucagon-like peptide-1-(9-36)amide by dipeptidyl peptidase IV in the capillaries supplying the L cells of the porcine intestine. Endocrinology 140, 5356–5363 (1999).CAS
PubMed
Article
PubMed Central
Google Scholar
58.Vahl, T. P. et al. Glucagon-like peptide-1 (GLP-1) receptors expressed on nerve terminals in the portal vein mediate the effects of endogenous GLP-1 on glucose tolerance in rats. Endocrinology 148, 4965–4973 (2007).CAS
PubMed
Article
PubMed Central
Google Scholar
59.Woerle, H. J., Carneiro, L., Derani, A., Göke, B. & Schirra, J. The role of endogenous incretin secretion as amplifier of glucose-stimulated insulin secretion in healthy subjects and patients with type 2 diabetes. Diabetes 61, 2349–2358 (2012).CAS
PubMed
PubMed Central
Article
Google Scholar
60.Chambers, A. P. et al. The role of pancreatic preproglucagon in glucose homeostasis in mice. Cell Metab. 25, 927–934.e3 (2017).CAS
PubMed
PubMed Central
Article
Google Scholar
61.Svendsen, B. et al. Insulin secretion depends on intra-islet glucagon signaling. Cell Rep. 25, 1127–1134.e2 (2018).CAS
PubMed
PubMed Central
Article
Google Scholar
62.de Heer, J., Rasmussen, C., Coy, D. H. & Holst, J. J. Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, inhibits glucagon secretion via somatostatin (receptor subtype 2) in the perfused rat pancreas. Diabetologia 51, 2263–2270 (2008).CAS
PubMed
Article
PubMed Central
Google Scholar
63.Gasbjerg, L. S. et al. Evaluation of the incretin effect in humans using GIP and GLP-1 receptor antagonists. Peptides 125, 170183 (2020).CAS
PubMed
Article
PubMed Central
Google Scholar
64.Wu, T., Rayner, C. K., Young, R. L. & Horowitz, M. Gut motility and enteroendocrine secretion. Curr. Opin. Pharmacol. 13, 928–934 (2013).CAS
PubMed
Article
PubMed Central
Google Scholar
65.Meier, J. J. GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat. Rev. Endocrinol. 8, 728–742 (2012).CAS
PubMed
Article
PubMed Central
Google Scholar
66.Krieger, J. P. et al. Knockdown of GLP-1 receptors in vagal afferents affects normal food intake and glycemia. Diabetes 65, 34–43 (2016).CAS
PubMed
PubMed Central
Google Scholar
67.Nauck, M. A., Quast, D. R., Wefers, J. & Meier, J. J. GLP-1 receptor agonists in the treatment of type 2 diabetes: state-of-the-art. Mol. Metab. https://doi.org/10.1016/j.molmet.2020.101102 (2020).Article
PubMed
PubMed Central
Google Scholar
68.Knudsen, L. B. & Lau, J. The discovery and development of liraglutide and semaglutide. Front. Endocrinol. (Lausanne) 10, 155 (2019).Article
Google Scholar
69.Jepsen, S. L. et al. Paracrine crosstalk between intestinal L- and D-cells controls secretion of glucagon-like peptide-1 in mice. Am. J. Physiol. Endocrinol. Metab. 317, E1081–E1093 (2019).CAS
PubMed
PubMed Central
Article
Google Scholar
70.Svane, M. S. et al. Peptide YY and glucagon-like peptide-1 contribute to decreased food intake after Roux-en-Y gastric bypass surgery. Int. J. Obes. (Lond) 40, 1699–1706 (2016).CAS
Article
Google Scholar
71.Williams, E. K. et al. Sensory neurons that detect stretch and nutrients in the digestive system. Cell 166, 209–221 (2016).CAS
PubMed
PubMed Central
Article
Google Scholar
72.Lu, V. B. et al. Adenosine triphosphate is co-secreted with glucagon-like peptide-1 to modulate intestinal enterocytes and afferent neurons. Nat. Commun. 10, 1029 (2019).PubMed
PubMed Central
Article
CAS
Google Scholar
73.Trapp, S. & Cork, S. C. PPG neurons of the lower brain stem and their role in brain GLP-1 receptor activation. Am. J. Physiol. Regul. Integr. Comp. Physiol. 309, R795–R804 (2015).CAS
PubMed
PubMed Central
Article
Google Scholar
74.Kreisler, A. D. & Rinaman, L. Hindbrain glucagon-like peptide-1 neurons track intake volume and contribute to injection stress-induced hypophagia in meal-entrained rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 310, R906–R916 (2016).PubMed
PubMed Central
Article
Google Scholar
75.Holt, M. K. et al. Preproglucagon neurons in the nucleus of the solitary tract are the main source of brain GLP-1, mediate stress-induced hypophagia, and limit unusually large intakes of food. Diabetes 68, 21–33 (2019).CAS
PubMed
Article
PubMed Central
Google Scholar
76.Cheng, W. et al. Leptin receptor-expressing nucleus tractus solitarius neurons suppress food intake independently of GLP1 in mice. JCI Insight 5, 134359 (2020).PubMed
Article
PubMed Central
Google Scholar
77.Sun, F. et al. Impact of GLP-1 receptor agonists on blood pressure, heart rate and hypertension among patients with type 2 diabetes: a systematic review and network meta-analysis. Diabetes Res. Clin. Pract. 110, 26–37 (2015).CAS
PubMed
Article
PubMed Central
Google Scholar
78.Giblett, J. P., Clarke, S. J., Dutka, D. P. & Hoole, S. P. Glucagon-like peptide-1: a promising agent for cardioprotection during myocardial ischemia. JACC Basic Transl. Sci. 1, 267–276 (2016).PubMed
PubMed Central
Article
Google Scholar
79.Holt, M. K. et al. PPG neurons in the nucleus of the solitary tract modulate heart rate but do not mediate GLP-1 receptor agonist-induced tachycardia in mice. Mol. Metab. 39, 101024 (2020).CAS
PubMed
PubMed Central
Article
Google Scholar
80.Müller, T. D. et al. Glucagon-like peptide 1 (GLP-1). Mol. Metab. 30, 72–130 (2019).PubMed
PubMed Central
Article
CAS
Google Scholar
81.Cheng, H. & Leblond, C. P. Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. III. Entero-endocrine cells. Am. J. Anat. 141, 503–519 (1974).CAS
PubMed
PubMed Central
Google Scholar
82.Mumphrey, M. B., Patterson, L. M., Zheng, H. & Berthoud, H. R. Roux-en-Y gastric bypass surgery increases number but not density of CCK-, GLP-1-, 5-HT-, and neurotensin-expressing enteroendocrine cells in rats. Neurogastroenterol. Motil. 25, e70–e79 (2013).CAS
PubMed
Article
PubMed Central
Google Scholar
83.Nauck, M., Stöckmann, F., Ebert, R. & Creutzfeldt, W. Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia 29, 46–52 (1986).CAS
PubMed
Article
PubMed Central
Google Scholar
84.Vollmer, K. et al. Hyperglycemia acutely lowers the postprandial excursions of glucagon-like peptide-1 and gastric inhibitory polypeptide in humans. J. Clin. Endocrinol. Metab. 94, 1379–1385 (2009).CAS
PubMed
Article
PubMed Central
Google Scholar
85.Wang, J. et al. Mutant neurogenin-3 in congenital malabsorptive diarrhea. N. Engl. J. Med. 355, 270–280 (2006).CAS
PubMed
Article
PubMed Central
Google Scholar
86.Jackson, R. S. et al. Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency. J. Clin. Invest. 112, 1550–1560 (2003).CAS
PubMed
PubMed Central
Article
Google Scholar
87.Kay, R. G. et al. Peptidomic analysis of endogenous plasma peptides from patients with pancreatic neuroendocrine tumours. Rapid Commun. Mass Spectrom. 32, 1414–1424 (2018).CAS
PubMed
PubMed Central
Article
Google Scholar
88.Tan, M., Lamendola, C., Luong, R., McLaughlin, T. & Craig, C. Safety, efficacy and pharmacokinetics of repeat subcutaneous dosing of avexitide (exendin 9-39) for treatment of post-bariatric hypoglycaemia. Diabetes Obes. Metab. 22, 1406–1416 (2020).CAS
PubMed
Article
PubMed Central
Google Scholar
89.Deacon, C. F. Peptide degradation and the role of DPP-4 inhibitors in the treatment of type 2 diabetes. Peptides 100, 150–157 (2018).CAS
PubMed
Article
PubMed Central
Google Scholar
90.Thethi, T. K., Pratley, R. & Meier, J. J. Efficacy, safety and cardiovascular outcomes of once-daily oral semaglutide in patients with type 2 diabetes: The PIONEER programme. Diabetes Obes. Metab. 22, 1263–1277 (2020).CAS
PubMed
PubMed Central
Article
Google Scholar
91.Zhang, X. et al. Differential GLP-1R binding and activation by peptide and non-peptide agonists. Mol. Cell 80, 485–500.e7 (2020).CAS
PubMed
Article
PubMed Central
Google Scholar
92.Lucey, M. et al. Disconnect between signalling potency and in vivo efficacy of pharmacokinetically optimised biased glucagon-like peptide-1 receptor agonists. Mol. Metab. 37, 100991 (2020).CAS
PubMed
PubMed Central
Article
Google Scholar
93.Tschöp, M. H. et al. Unimolecular polypharmacy for treatment of diabetes and obesity. Cell Metab. 24, 51–62 (2016).PubMed
Article
CAS
PubMed Central
Google Scholar
94.Frias, J. P. et al. Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a randomised, placebo-controlled and active comparator-controlled phase 2 trial. Lancet 392, 2180–2193 (2018).CAS
PubMed
Article
PubMed Central
Google Scholar
95.Parker, V. E. R. et al. Efficacy, safety, and mechanistic insights of cotadutide, a dual receptor glucagon-like peptide-1 and glucagon agonist. J. Clin. Endocrinol. Metab. 105, dgz047 (2020).PubMed
Article
PubMed Central
Google Scholar
96.Ämmälä, C. et al. Targeted delivery of antisense oligonucleotides to pancreatic β-cells. Sci. Adv. 4, eaat3386 (2018).PubMed
PubMed Central
Article
CAS
Google Scholar
97.Reiner, T. et al. Accurate measurement of pancreatic islet beta-cell mass using a second-generation fluorescent exendin-4 analog. Proc. Natl. Acad. Sci. USA 108, 12815–12820 (2011).CAS
PubMed
Article
PubMed Central
Google Scholar
