Amino terminal glycation of gastric inhibitory polypeptide enhances its insulinotropic action on clonal pancreatic B-cells

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Abstract

Gastric inhibitory polypeptide (GIP) is a potent insulin-releasing hormone of the enteroinsular axis. This study has examined glycation of GIP and effects of such structural modification on insulin secretion from a glucose-responsive clonal pancreatic B-cell line (BRIN-BD11). Monoglycated GIP (M-r 5149.5) was prepared by incubation with D-glucose under reducing conditions and purified by HPLC. Automated Edman degradation and mass spectrometric analysis indicated that GIP was specifically glycated at the amino terminus. Tn acute (20 min) incubations at 5.6 mM glucose, GIP (3 X 10(-11)-10(-8) M) significantly stimulated insulin secretion by 1.6-2.1-fold from BRIN-BD11 cells. The stimulatory effect induced by GIP over this concentration range was further enhanced by 1.5-2.5-fold following N-terminal glycation. These data indicate that GIP can be glycated under hyperglycaemic conditions at the amino terminal Tyr(1), and that this modification increases the glucose-dependent insulinotropic action of the peptide. (C) 1998 Elsevier Science B.V. All rights reserved.
LanguageEnglish
Pages319-327
JournalBIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
Volume1425
Issue number2
Publication statusPublished - Oct 1998

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Gastric Inhibitory Polypeptide
Insulin-Secreting Cells
Insulin
Glucose
High Pressure Liquid Chromatography
Hormones
Cell Line

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title = "Amino terminal glycation of gastric inhibitory polypeptide enhances its insulinotropic action on clonal pancreatic B-cells",
abstract = "Gastric inhibitory polypeptide (GIP) is a potent insulin-releasing hormone of the enteroinsular axis. This study has examined glycation of GIP and effects of such structural modification on insulin secretion from a glucose-responsive clonal pancreatic B-cell line (BRIN-BD11). Monoglycated GIP (M-r 5149.5) was prepared by incubation with D-glucose under reducing conditions and purified by HPLC. Automated Edman degradation and mass spectrometric analysis indicated that GIP was specifically glycated at the amino terminus. Tn acute (20 min) incubations at 5.6 mM glucose, GIP (3 X 10(-11)-10(-8) M) significantly stimulated insulin secretion by 1.6-2.1-fold from BRIN-BD11 cells. The stimulatory effect induced by GIP over this concentration range was further enhanced by 1.5-2.5-fold following N-terminal glycation. These data indicate that GIP can be glycated under hyperglycaemic conditions at the amino terminal Tyr(1), and that this modification increases the glucose-dependent insulinotropic action of the peptide. (C) 1998 Elsevier Science B.V. All rights reserved.",
author = "Finbarr O'Harte and Yasser Abdel-Wahab and JM Conlon and Peter Flatt",
year = "1998",
month = "10",
language = "English",
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pages = "319--327",
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TY - JOUR

T1 - Amino terminal glycation of gastric inhibitory polypeptide enhances its insulinotropic action on clonal pancreatic B-cells

AU - O'Harte, Finbarr

AU - Abdel-Wahab, Yasser

AU - Conlon, JM

AU - Flatt, Peter

PY - 1998/10

Y1 - 1998/10

N2 - Gastric inhibitory polypeptide (GIP) is a potent insulin-releasing hormone of the enteroinsular axis. This study has examined glycation of GIP and effects of such structural modification on insulin secretion from a glucose-responsive clonal pancreatic B-cell line (BRIN-BD11). Monoglycated GIP (M-r 5149.5) was prepared by incubation with D-glucose under reducing conditions and purified by HPLC. Automated Edman degradation and mass spectrometric analysis indicated that GIP was specifically glycated at the amino terminus. Tn acute (20 min) incubations at 5.6 mM glucose, GIP (3 X 10(-11)-10(-8) M) significantly stimulated insulin secretion by 1.6-2.1-fold from BRIN-BD11 cells. The stimulatory effect induced by GIP over this concentration range was further enhanced by 1.5-2.5-fold following N-terminal glycation. These data indicate that GIP can be glycated under hyperglycaemic conditions at the amino terminal Tyr(1), and that this modification increases the glucose-dependent insulinotropic action of the peptide. (C) 1998 Elsevier Science B.V. All rights reserved.

AB - Gastric inhibitory polypeptide (GIP) is a potent insulin-releasing hormone of the enteroinsular axis. This study has examined glycation of GIP and effects of such structural modification on insulin secretion from a glucose-responsive clonal pancreatic B-cell line (BRIN-BD11). Monoglycated GIP (M-r 5149.5) was prepared by incubation with D-glucose under reducing conditions and purified by HPLC. Automated Edman degradation and mass spectrometric analysis indicated that GIP was specifically glycated at the amino terminus. Tn acute (20 min) incubations at 5.6 mM glucose, GIP (3 X 10(-11)-10(-8) M) significantly stimulated insulin secretion by 1.6-2.1-fold from BRIN-BD11 cells. The stimulatory effect induced by GIP over this concentration range was further enhanced by 1.5-2.5-fold following N-terminal glycation. These data indicate that GIP can be glycated under hyperglycaemic conditions at the amino terminal Tyr(1), and that this modification increases the glucose-dependent insulinotropic action of the peptide. (C) 1998 Elsevier Science B.V. All rights reserved.

M3 - Article

VL - 1425

SP - 319

EP - 327

IS - 2

ER -