Transgenic pig with altered incretin function

A transgenic pig whose genome comprises a recombinant nucleic acid encoding a dominant-negative human glucose-dependent insulinotropic polypeptide receptor (GIPRdn) operably linked to an insulin promoter that results in expression of the dominant-negative human glucose-dependent insulinotropic polypeptide receptor (GIPRdn), wherein said pig expresses the dominant-negative human glucose-dependent insulinotropic polypeptide receptor (GIPRdn), and wherein said pig exhibits, as a result of the expression of said receptor, at least one of:

• a) an elevated glucose level following an oral glucose load;
• b) reduced or delayed insulin secretion;
• c) reduced oral glucose tolerance;
• d) reduced pancreatic islet and β-cell mass;
• and
• e) impaired glucose-dependent insulinotropic polypeptide (GIP) function.