• Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA

Homologous and heterologous competition experiments were performed with non-radioactive peptide analogues[127I]-Tyr1-GIP(1-42) and [127]-Tyr10-GIP(1-42) to ensure quantification of the high-affinity binding site of the GIPR. Peptide analogues were generated using synthetic [127I]-Tyr amino acid building blocks (CPC Scientific).

1. Discovery Chemistry Research and Technologies, Diabetes and Complications, Investigative Drug Disposition, Lilly Research Laboratories, Indianapolis, IN 46285 and S2.
2. Discovery Chemistry Research and Technologies, Lilly, S.A., Avda. de la Industria 30, 28108 Alcobendas, Madrid, Spain.

Synthetic peptides were synthesized at Eli Lilly, Bachem (Torrance, CA), or CPC Scientific (Sunnyvale, CA) to >95% purity.

1. Lilly, S.A., Alcobendas, Spain.
2. ConfometRx, Santa Clara, CA, USA.
3. Departments of Quantitative Biology, Discovery Chemistry Research and Technologies, and Diabetes and Complications, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
4. Lilly Biotechnology Center San Diego, San Diego, CA, USA.

Peptides were synthesized and purified to >95% purity at Eli Lilly and Company or purchased from CPC Scientific or Tocris. GLP-1(9-36)NH2, GLP-1(7-36)NH2, OXM(1-37)OH and GIP(1-42)NH2 were used for pharmacology experiments, and GLP-1(7-37)OH was used for cryo-EM studies.

1. Fractyl Laboratories Inc, Lexington, MA, 02421, USA
2. Diabetes Research Group, School of Life Course Sciences, Faculty of Life Science and Medicine, King’s College London, London, WC2R 2LS, England, UK

[..] infusion of vehicle 2 via osmotic minipump; (2) glucagon-like peptide-1 receptor (GLP-1R) agonist (0.2 mg/kg liraglutide, SC, QD, Victoza (Novo Nordisk, Bagsværd, Denmark) and continuous infusion of vehicle 2 via osmotic minipump; (3) vehicle 1 (SC, QD) and continuous infusion of a glucose-dependent insulinotropic polypeptide receptor (GIPR) antagonist (∼4.5 mg/kg/day / 56.8 nmol/kg/h GIP[3-30]NH2, CPC Scientific Inc, Sunnyvale, CA, USA) via osmotic minipump;

1. Cardiovascular and Metabolic Diseases, MedImmune Ltd, Milstein Building, Granta Park, Cambridge, CB21 6GH, UK
2. University of Cambridge, Department of Clinical Biochemistry, MRC Metabolic Diseases Unit, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK
3. Cardiovascular and Metabolic Diseases, MedImmune LLC, One MedImmune Way, Gaithersburg, MD 20878, USA

AC3174 (Amylin Pharmaceuticals) is a functional analog of exenatide (Hargrove et al., 2007). AC170222 (Hpa-Nle-Gly-Trp-Lys(Tac)-Asp-NMePhe-NH2; CPC Scientific, Sunnyvale, CA) is a CCKR1-selective peptide (Pierson et al., 2000).

• 1 Lilly Research Laboratories, Eli Lilly & Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.

"The OXM peptides 1–37, 3–37 and 4–37 as well as their corresponding stable isotope-labeled internal standards (each containing one [ 13 C 9 , 15 N]-labeled phenylalanine and two [ 13 C 6 , 15 N]-labeled leucine residues) were synthesized by CPC Scientific, Inc."

• Cardio-metabolic Disease Biomarkers, Merck Research Laboratories, Kenilworth, NJ., Merck & Co., Inc.

"Glucagon synthetic peptide and heavy isotope–labeled internal standards (ISs) of oxyntomodulin and glucagon containing 2 [ 13 C 6 - 15 N]-labeled leucines and 1 [ 13 C 9 - 15 N]-labeled phenylalanine were synthesized by CPC Scientific.."

• Departments of Cardiometabolic Diseases and In Vivo Pharmacology, Merck Research Laboratories, 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA

GLP-1 was purchased from CPC Scientific (San Jose, California). MK-0626 was synthesized by Merck & Co., Inc.