Triple glucagon/GLP-1/GIP receptor agonist

An isolated peptide having activities to a glucagon receptor, a glucagon-like peptide-1 (GLP-1) receptor, and a glucose-dependent insulinotropic polypeptide (GIP) receptor,

• wherein the isolated peptide comprises the amino acid sequence of the following Formula (1):
• (SEQ ID NO:
• 103)
• Xaa1-Xaa2-Xaa3-Gly-Thr-Phe-Xaa7-Ser-Asp-Xaa10-Ser-
• Xaa12-Xaa13-Xaa14-Xaa15-Xaa16-Xaa17-Xaa18-Xaa19-
• Xaa20-Xaa21-Phe-Xaa23-Xaa24-Trp-Leu-Xaa27-Xaa28-
• Xaa29-Xaa30-R1
• wherein, in Formula (1),
• Xaa1 is His, 4-imidazoacetyl (CA), or Tyr;
• Xaa2 is α-methyl-glutamic acid, or aminoisobutyric acid (Aib);
• Xaa3 is Gln;
• Xaa7 is Thr;
• Xaa10 is Tyr;
• Xaa12 is Lys;
• Xaa13 is Tyr, Ala, or Cys;
• Xaa14 is Leu or Met;
• Xaa15 is Cys, Asp, or Glu;
• Xaa16 is Gly or Glu;
• Xaa17 is Gln, Arg, Ile, Glu, Cys, or Lys;
• Xaa18 is Ala, Arg, or His;
• Xaa19 is Ala, Gln, or Cys;
• Xaa20 is Lys;
• Xaa21 is Glu, Gln, Cys, or Asp;
• Xaa23 is Ile or Val;
• Xaa24 is Ala, Gln, Cys, or Asn;
• Xaa27 is Leu or Lys;
• Xaa28 is Cys, Ala, or Asp;
• Xaa29 is Cys, Gly, Gln, Thr, Glu, or His;
• Xaa30 is Cys, Gly, Lys, or His, or is absent;
• and
• R1 is Cys, GKKNDWKHNIT (SEQ ID NO:
• 106), m-SSGAPPPS-n (SEQ ID NO:
• 107), or m-SSGQPPPS-n (SEQ ID NO:
• 108), or is absent;
• wherein
• m is -Cys-, -Pro-, or -Gly-Pro-;
• and
• n is -Cys-, -Gly-, -Ser-, or -His-Gly-, or is absent.