O'Harte, Finbarr, Mooney, MH and Flatt, Peter (1999) NH2-terminally modified gastric inhibitory polypeptide exhibits amino-peptidase resistance and enhanced antihyperglycemic activity. DIABETES, 48 (4). pp. 758-765. [Journal article]
Full text not available from this repository.
Gastric inhibitory polypeptide (GIP) is an important insulin-releasing hormone of the enteroinsular axis that, like glucagon-like peptide 1(7-36) amide (tGLP-I), has a functional profile of possible therapeutic value for type 2 diabetes, Both incretin hormones are rapidly inactivated in plasma by the exopeptidase dipeptidyl peptidase (DPP) IV, The present study examined the ability of NH2-terminal modification of human GIP to protect Born plasma degradation and enhance insulin-releasing and antihyperglycemic activity Degradation of GIP by incubation at 37 degrees C with purified DPP IV was clearly evident after 4 h (54% intact). After 12 h, >60% of GIP was converted to GIP(3-42), whereas >99% of NH2-terminally modified Tyr(1)-glucitol GIP remained intact. Tyr(1)-glucitol GIP was similarly resistant to serum degradation. The formation of GIP(3-42) was almost completely abolished by inhibition of plasma DPP IV with diprotin A, Effects of GIP and Tyr(1)-glucitol GIP were examined in Wistar rats after intraperitoneal injection of either peptide (10 nmol/kg) together with glucose (18 mmol/kg), Plasma glucose concentrations were significantly lower and insulin concentrations higher after both peptides compared with glucose alone. More importantly, individual glucose values at 15 and 30 min together with the areas under the curve (AUCs) for glucose were significantly lower after administration of Tyr(1)-glucitol GIP compared with GIP (AUC 255 +/- 33 vs. 368 +/- 8 mmol.l(-1).min(-1), respectively; P < 0.01), This was associated with a significantly greater and more protracted insulin response after Tyr(1)-glucitol GIP than GIP (AUC 773 +/- 41 vs. 639 +/- 39 ng.ml(-1).min(-1) P < 0.05). These data demonstrate that Tyr(1)-glucitol GIP displays resistance to plasma DPP IV degradation and exhibits enhanced antihyperglycemic activity and insulin-releasing action in vivo.
|Item Type:||Journal article|
|Faculties and Schools:||Faculty of Life and Health Sciences|
Faculty of Life and Health Sciences > School of Biomedical Sciences
|Research Institutes and Groups:||Biomedical Sciences Research Institute|
Biomedical Sciences Research Institute > Diabetes
|Deposited By:||Professor Peter Flatt|
|Deposited On:||08 Jan 2010 15:23|
|Last Modified:||11 Jun 2010 11:48|
Repository Staff Only: item control page