Pancreatic polypeptide family motifs, polypeptides and methods comprising the same

1. A method for treating Type-2 diabetes, obesity, or insulin-resistance syndrome, or for causing weight loss, in a mammal in need thereof, the method comprising administering to the mammal a therapeutically effective amount of a PPF polypeptide to treat obesity, Type-2 diabetes, or insulin-resistance syndrome, or to cause weight loss, wherein the PPF polypeptide comprises the amino acid sequence of Formula (VII) (SEQ ID NO: 482):

Xaa 1  Xaa 2  Pro Xaa 4  Pro Xaa 6  His Pro Xaa 9  Xaa 10

Xaa 11  Xaa 12  Xaa 13  Xaa 14  Xaa 15  Xaa 16  Xaa 17  Ala

Xaa 19  Tyr Xaa 21  Xaa 22  Xaa 23  Leu Xaa 25  Xaa 26  Xaa 27

Xaa 28  Xaa 29  Xaa 30  Xaa 31  Thr Arg Gln Arg Tyr

wherein:

Xaa 1 is absent;

Xaa 2 is absent;

Xaa 4 is Lys;

Xaa 6 is Glu;

Xaa 9 is Gly;

Xaa 10 is Glu;

Xaa 11 is Asp;

Xaa 12 is Ala;

Xaa 13 is Ser or Pro;

Xaa 14 is Pro, Ala, or Ser;

Xaa 15 is Glu;

Xaa 16 is Glu;

Xaa 17 is Leu;

Xaa 19 is Arg, Lys;

Xaa 21 is Tyr;

Xaa 22 is Ala;

Xaa 23 is Ser;

Xaa 25 is Arg;

Xaa 26 is Ala;

Xaa 27 is Tyr;

Xaa 28 is Ile;

Xaa 29 is Asn;

Xaa 30 is Leu; and

Xaa 31 is Ile.

2. The method of claim 1 for treating Type 2 diabetes.

3. The method of claim 1 for treating obesity in the mammal in need thereof.

4. The method of claim 1 , wherein the PPF polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 438.

5. The method of claim 1 , wherein the PPF polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 266, 437, 438, 439, 442, 462, 469, 470, 471, and 472.

6. The method of claim 1 , wherein the PPF polypeptide further comprises an N-terminal cap.

7. The method of claim 1 , wherein the PPF polypeptide is linked to one or more water-soluble polymers.

8. The method of claim 7 , wherein the polymer is selected from at least one of the group consisting of polyethylene glycol and a fatty acid molecule, wherein the polymer is linked to the N- or C-terminus of the polypeptide, or the side chain of a lysine or serine amino acid residue within the sequence of the polypeptide.