Improved stability, insulin-releasing activity and antidiabetic potential of two novel N-terminal analogues of gastric inhibitory polypeptide: N-acetyl-GIP and pGlu-GIP

Finbarr O'Harte, Victor Gault, JC Parker, P Harriott, MH Mooney, CJ Bailey, Peter Flatt

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Abstract

Aims/hypothesis. This study examined the plasma stability, biological activity and antidiabetic potential of two novel N-terminally modified analogues of gastric inhibitory polypeptide (GIP). Methods. Degradation studies were carried out on GIP, N-acetyl-GIP (Ac-GIP) and N-pyroglutamyl-GIP (pGlu-GIP) in vitro following incubation with either dipeptidylpeptidase IV or human plasma. Cyclic adenosine 3'5' monophosphate (CAMP) production was assessed in Chinese hamster lung fibroblast cells transfected with the human GIP receptor. Insulin-releasing ability was assessed in vitro in BRIN-BD11 cells and in obese diabetic (ob/ob) mice. Results. GIP was rapidly degraded by dipeptidylpeptidase IV and plasma (t(1/2) 2.3 and 6.2 h, respectively) whereas Ac-GIP and pGlu-GIP remained intact even after 24 h. Both Ac-GIP and pGlu-GIP were extremely potent (p
Original languageEnglish
Pages (from-to)1281-1291
JournalDiabetologia
Volume45
Issue number9
DOIs
Publication statusPublished - Sep 2002

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Gastric Inhibitory Polypeptide
Hypoglycemic Agents
Insulin
Cricetulus
Adenosine
Fibroblasts
Lung

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title = "Improved stability, insulin-releasing activity and antidiabetic potential of two novel N-terminal analogues of gastric inhibitory polypeptide: N-acetyl-GIP and pGlu-GIP",
abstract = "Aims/hypothesis. This study examined the plasma stability, biological activity and antidiabetic potential of two novel N-terminally modified analogues of gastric inhibitory polypeptide (GIP). Methods. Degradation studies were carried out on GIP, N-acetyl-GIP (Ac-GIP) and N-pyroglutamyl-GIP (pGlu-GIP) in vitro following incubation with either dipeptidylpeptidase IV or human plasma. Cyclic adenosine 3'5' monophosphate (CAMP) production was assessed in Chinese hamster lung fibroblast cells transfected with the human GIP receptor. Insulin-releasing ability was assessed in vitro in BRIN-BD11 cells and in obese diabetic (ob/ob) mice. Results. GIP was rapidly degraded by dipeptidylpeptidase IV and plasma (t(1/2) 2.3 and 6.2 h, respectively) whereas Ac-GIP and pGlu-GIP remained intact even after 24 h. Both Ac-GIP and pGlu-GIP were extremely potent (p",
author = "Finbarr O'Harte and Victor Gault and JC Parker and P Harriott and MH Mooney and CJ Bailey and Peter Flatt",
year = "2002",
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doi = "10.1007/s00125-002-0894-6",
language = "English",
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pages = "1281--1291",
journal = "Diabetologia",
issn = "0012-186X",
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TY - JOUR

T1 - Improved stability, insulin-releasing activity and antidiabetic potential of two novel N-terminal analogues of gastric inhibitory polypeptide: N-acetyl-GIP and pGlu-GIP

AU - O'Harte, Finbarr

AU - Gault, Victor

AU - Parker, JC

AU - Harriott, P

AU - Mooney, MH

AU - Bailey, CJ

AU - Flatt, Peter

PY - 2002/9

Y1 - 2002/9

N2 - Aims/hypothesis. This study examined the plasma stability, biological activity and antidiabetic potential of two novel N-terminally modified analogues of gastric inhibitory polypeptide (GIP). Methods. Degradation studies were carried out on GIP, N-acetyl-GIP (Ac-GIP) and N-pyroglutamyl-GIP (pGlu-GIP) in vitro following incubation with either dipeptidylpeptidase IV or human plasma. Cyclic adenosine 3'5' monophosphate (CAMP) production was assessed in Chinese hamster lung fibroblast cells transfected with the human GIP receptor. Insulin-releasing ability was assessed in vitro in BRIN-BD11 cells and in obese diabetic (ob/ob) mice. Results. GIP was rapidly degraded by dipeptidylpeptidase IV and plasma (t(1/2) 2.3 and 6.2 h, respectively) whereas Ac-GIP and pGlu-GIP remained intact even after 24 h. Both Ac-GIP and pGlu-GIP were extremely potent (p

AB - Aims/hypothesis. This study examined the plasma stability, biological activity and antidiabetic potential of two novel N-terminally modified analogues of gastric inhibitory polypeptide (GIP). Methods. Degradation studies were carried out on GIP, N-acetyl-GIP (Ac-GIP) and N-pyroglutamyl-GIP (pGlu-GIP) in vitro following incubation with either dipeptidylpeptidase IV or human plasma. Cyclic adenosine 3'5' monophosphate (CAMP) production was assessed in Chinese hamster lung fibroblast cells transfected with the human GIP receptor. Insulin-releasing ability was assessed in vitro in BRIN-BD11 cells and in obese diabetic (ob/ob) mice. Results. GIP was rapidly degraded by dipeptidylpeptidase IV and plasma (t(1/2) 2.3 and 6.2 h, respectively) whereas Ac-GIP and pGlu-GIP remained intact even after 24 h. Both Ac-GIP and pGlu-GIP were extremely potent (p

U2 - 10.1007/s00125-002-0894-6

DO - 10.1007/s00125-002-0894-6

M3 - Article

VL - 45

SP - 1281

EP - 1291

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 9

ER -