Therapeutic potential of the original incretin hormone glucose-dependent insulinotropic polypeptide: diabetes, obesity, osteoporosis and Alzheimer's disease?
BACKGROUND
Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone that potentiates nutrient-induced insulin release. To date, the physiological importance of GIP has received much less attention than its younger sister incretin hormone glucagon-like peptide-1. Thus, it is worthwhile to refocus on this important and somewhat neglected incretin hormone.


METHODS
The potential role of GIP as a treatment option for type 2 diabetes is highlighted. Furthermore, the use of GIP as a new therapeutic option for obesity, osteoporosis and cognitive impairment is also considered.


RESULTS
Long-acting GIP receptor agonists offer a potential new class of antidiabetic drugs. Furthermore, recent observations suggest an as yet untapped potential for GIP agonists in the treatment of osteoporosis and cognitive impairment. In addition, GIP is known to play a role in lipid metabolism and fat deposition. Accordingly, both genetic and chemical ablation of GIP signalling in mice with obesity-diabetes can protect against, or reverse, many of the obesity-associated metabolic disturbances. This review focuses on preclinical data generated to date.


CONCLUSIONS
GIP-based therapeutics have potential for the treatment of type 2 diabetes and obesity, with the possibility of further beneficial actions in osteoporosis and cognitive decline.
Irwin
Nigel
N
SAAD Centre for Diabetes and Pharmacy, School of Biomedical Sciences, University of Ulster, Cromore Road, Coleraine, Co. Londonderry, BT52 1SA, Northern Ireland, UK. n.irwin@ulster.ac.uk
Gault
Victor
V
Flatt
Peter R
PR
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology; D005749:Gastric Inhibitory Polypeptide / Q000819:agonists / Q000031:analogs & derivatives / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism; D010024:Osteoporosis / Q000188:drug therapy / Q000378:metabolism; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy / Q000378:metabolism; D011964:Receptors, Gastrointestinal Hormone / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism
D007004:Hypoglycemic Agents; D011964:Receptors, Gastrointestinal Hormone; D005749:Gastric Inhibitory Polypeptide; C041086:gastric inhibitory polypeptide receptor