In:
American Journal of Physiology-Endocrinology and Metabolism, American Physiological Society, Vol. 292, No. 6 ( 2007-06), p. E1674-E1682
Abstract:
This study examines the actions of the novel enzyme-resistant, NH 2 -terminally modified GIP analog (Hyp 3 )GIP and its fatty acid-derivatized analog (Hyp 3 )GIPLys 16 PAL. Acute effects are compared with the established GIP receptor antagonist (Pro 3 )GIP. All three peptides exhibited DPP IV resistance, and significantly inhibited GIP stimulated cAMP formation and insulin secretion in GIP receptor-transfected fibroblasts and in clonal pancreatic BRIN-BD11 cells, respectively. Likewise, in obese diabetic ob/ob mice, intraperitoneal administration of GIP analogs significantly inhibited the acute antihyperglycemic and insulin-releasing effects of native GIP. Administration of once daily injections of (Hyp 3 )GIP or (Hyp 3 )GIPLys 16 PAL for 14 days resulted in significantly lower plasma glucose levels ( P 〈 0.05) after (Hyp 3 )GIP on days 12 and 14 and enhanced glucose tolerance ( P 〈 0.05) and insulin sensitivity ( P 〈 0.05 to P 〈 0.001) in both groups by day 14. Both (Hyp 3 )GIP and (Hyp 3 )GIPLys 16 PAL treatment also reduced pancreatic insulin ( P 〈 0.05 to P 〈 0.01) without affecting islet number. These data indicate that (Hyp 3 )GIP and (Hyp 3 )GIPLys 16 PAL function as GIP receptor antagonists with potential for ameliorating obesity-related diabetes. Acylation of (Hyp 3 )GIP to extend bioactivity does not appear to be of any additional benefit.
Type of Medium:
Online Resource
ISSN:
0193-1849
,
1522-1555
DOI:
10.1152/ajpendo.00391.2006
Language:
English
Publisher:
American Physiological Society
Publication Date:
2007
detail.hit.zdb_id:
1477331-4
SSG:
12
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