Ghrh agonists for islet cell transplantation and function and the treatment of diabetes

A method of promoting survival of grafted tissue, the method comprising exposing the tissue to an effective amount of a GHRH agonist peptide, wherein the GHRH agonist peptide has the formula:

• [R1-A1-A2-Asp-Ala-Ile-A6-Thr-A8-Ser-Tyr-A11-A12-Val-Leu-A15-Gln-Leu-Ser-Ala-A20-A21-A22-Leu-Gln-Asp-Ile-Nle27-A28-A29-A30]-R2,
• wherein R1 is Ac, Tfa, or is absent,
• A1 is Tyr, Dat, or N-Me-Tyr,
• A2 is Ala, D-Ala, Abu, or D-Abu,
• A6 is Phe or Fpa5,
• A8 is Asn, Ala, Gln, Thr, or N-Me-Ala,
• A11 is Arg, H is, or Har,
• A12 is Orn, or Lys(Me)2,
• A15 is Abu or Ala,
• A20 is Arg, His, or Har,
• A21 is Orn, or Lys(Me)2,
• A22 is Leu, or Orn,
• A28 is Ser, or Asp,
• A29 is Arg, Har, Agm, D-Arg, or D-Har,
• A30 is Arg, Agm, Ada, Amc, Aha, Apa, Har, D-Arg, D-Har, Gab, Gln, D-Gln, Gln-Gab, D-Gln-Gab, or is absent,
• R2 is —NH2, —NH—CH3, NH—CH2—CH3, —OH, —NHR3, —N(R3)2, or —OR3, wherein R3 is any of C1-12 alkyl, C2-12 alkenyl, or C2-12 alkynyl,
• and pharmaceutically acceptable salts thereof, and wherein the agonist peptide is different from SEQ ID NO:
• 1 in at least one amino acid residue.

A method of modulating a function of an insulin producing cell, the method comprising exposing the insulin producing cell to an effective amount of a GHRH agonist peptide, wherein the GHRH agonist peptide comprises a formula:

• [R1-A1-A2-Asp-Ala-Ile-A6-Thr-A8-Ser-Tyr-A11-A12-Val-Leu-A15-Gln-Leu-Ser-Ala-A20-A21-A22-Leu-Gln-Asp-Ile-Nle27-A28-A29-A30]R2,
• wherein R1 is Ac, Tfa, or is absent,
• A1 is Tyr, Dat, or N-Me-Tyr,
• A2 is Ala, D-Ala, Abu, or D-Abu,
• A6 is Phe or Fpa5,
• A8 is Asn, Ala, Gln, Thr, or N-Me-Ala,
• A11 is Arg, His, or Har,
• A12 is Orn, or Lys(Me)2,
• A15 is Abu or Ala,
• A20 is Arg, His, or Har,
• A21 is Orn, or Lys(Me)2,
• A22 is Leu, or Orn,
• A28 is Ser, or Asp,
• A29 is Arg, Har, Agm, D-Arg, or D-Har,
• A30 is Arg, Agm, Ada, Amc, Aha, Apa, Har, D-Arg, D-Har, Gab, Gln, D-Gln, Gln-Gab, D-Gln-Gab, or is absent,
• R2 is —NH2, —NH—CH3, NH—CH2—CH3, —OH, —NHR3, —N(R3)2, or —OR3, wherein R3 is any of C1-12 alkyl, C2-12 alkenyl, or C2-12 alkynyl,
• and pharmaceutically acceptable salts thereof, and wherein the agonist peptide is different from SEQ ID NO:
• 1 in at least one amino acid residue.

A method of transplanting insulin producing cells into a diabetic mammal in need thereof, the method comprising:

• transplanting the insulin producing cells into an adrenal gland of the diabetic mammal;
• and
• administering a therapeutically effective amount of a GHRH agonist peptide to the diabetic mammal, wherein the GHRH agonist peptide comprises a formula:
• [R1-A1-A2-Asp-Ala-Ile-A6-Thr-A8-Ser-Tyr-A11-A12-Val-Leu-A15-Gln-Leu-Ser-Ala-A20-A21-A22-Leu-Gln-Asp-Ile-Nle27-A28-A29-A30]-R2,
• wherein R1 is Ac, Tfa, or is absent,
• A1 is Tyr, Dat, or N-Me-Tyr,
• A2 is Ala, D-Ala, Abu, or D-Abu,
• A6 is Phe or Fpa5,
• A8 is Asn, Ala, Gln, Thr, or N-Me-Ala,
• A11 is Arg, His, or Har,
• A12 is Orn, or Lys(Me)2,
• A15 is Abu or Ala,
• A20 is Arg, His, or Har,
• A21 is Orn, or Lys(Me)2,
• A22 is Leu, or Orn,
• A28 is Ser, or Asp,
• A29 is Arg, Har, Agm, D-Arg, or D-Har,
• A30 is Arg, Agm, Ada, Amc, Aha, Apa, Har, D-Arg, D-Har, Gab, Gln, D-Gln, Gln-Gab, D-Gln-Gab, or is absent,
• R2 is —NH2, —NH—CH3, NH—CH2—CH3, —OH, —NHR3, —N(R3)2, or —OR3, wherein R3 is any of C1-12 alkyl, C2-12 alkenyl, or C2-12 alkynyl,
• and pharmaceutically acceptable salts thereof, and wherein the agonist peptide is different from SEQ ID NO:
• 1 in at least one amino acid residue.