Glucose-dependent insulinotropic polypeptide analogues and their therapeutic potential for the treatment of obesity-diabetes.
Glucose-dependent insulinotropic polypeptide (GIP) is a key incretin hormone, released postprandially into the circulation in response to feeding, producing a glucose-dependent stimulation of insulin secretion. It is this glucose-dependency that has attracted attention towards GIP as a potential therapeutic agent for the treatment of type 2 diabetes. A major drawback to achieving this goal has been the rapid degradation of circulating GIP by the ubiquitous enzyme, dipeptidylpeptidase IV (DPP IV). However, recent studies have described a number of novel structurally modified analogues of GIP with enhanced plasma stability, insulinotropic and antihyperglycaemic activity. The purpose of this article was to provide an overview of the biological effects of several GIP modifications and to highlight the potential of such analogues in the treatment of type 2 diabetes and obesity.
Gault
Victor A
VA
School of Biomedical Sciences, University of Ulster, Cromore Road, Coleraine BT52 1SA, Northern Ireland, UK. va.gault@ulster.ac.uk
Flatt
Peter R
PR
O'Harte
Finbarr P M
FP
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D015195:Drug Design; D005749:Gastric Inhibitory Polypeptide / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D008969:Molecular Sequence Data; D009765:Obesity / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use
D011994:Recombinant Proteins; D005749:Gastric Inhibitory Polypeptide; D018819:Dipeptidyl Peptidase 4