N-terminal glycation of cholecystokinin-8 abolishes its insulinotropic action on clonal pancreatic B-cells

Yasser H.A. Abdel-Wahab; Finbarr P.M. O'Harte; Mark H. Mooney; J. Michael Conlon; Peter R. Flatt

doi:10.1016/S0167-4889(99)00108-1

N-terminal glycation of cholecystokinin-8 abolishes its insulinotropic action on clonal pancreatic B-cells

Yasser H.A. Abdel-Wahab, Finbarr P.M. O'Harte, Mark H. Mooney, J. Michael Conlon, Peter R. Flatt

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

Abstract

Monoglycated cholecystokinin octapeptide (Asp¹-glucitol CCK-8) was prepared under hyperglycaemic reducing conditions and purified by reverse phase-high performance liquid chromatography. Electrospray ionisation mass spectrometry and automated Edman degradation demonstrated that CCK-8 was glycated specifically at the amino-terminal Asp¹ residue. Effects of Asp¹- glucitol CCK-8 and CCK-8 on insulin secretion were examined using glucose- responsive clonal BRIN-BD11 cells. In acute (20 min) incubations, 10^-10 mol/l CCK-8 enhanced insulin release by 1.2-1.5-fold at 5.6-11.1 mmol/l glucose. The stimulatory effect induced by 10^-10 mol/l CCK-8 was abolished following glycation. At 5.6 mmol/l glucose, CCK-8 at concentrations ranging from 10^-11 to 10^-7 mol/l induced a significant 1.6-1.9-fold increase in insulin secretion. Insulin output in the presence of Asp¹-glucitol CCK-8 over the concentration range 10^-11-10^-7 mol/l was decreased by 21-35% compared with CCK-8, and its insulinotropic action was effectively abolished. Asp¹-glucitol CCK-8 at 10^-8 mol/l also completely blocked the stimulatory effects of 10^-11-10^-8 mol/l CCK-8. These data indicate that structural modification by glycation at the amino-terminal Asp¹ residue effectively abolishes and/or antagonises the insulinotropic activity of CCK-8.

Original language	English
Pages (from-to)	60-67
Number of pages	8
Journal	Biochimica et Biophysica Acta - Molecular Cell Research
Volume	1452
Issue number	1
DOIs	https://doi.org/10.1016/S0167-4889(99)00108-1
Publication status	Published - Oct 13 1999
Externally published	Yes

Keywords

BRIN-BD11 cell
Cholecystokinin-8
Glycation
Insulin secretion

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/S0167-4889(99)00108-1

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title = "N-terminal glycation of cholecystokinin-8 abolishes its insulinotropic action on clonal pancreatic B-cells",

abstract = "Monoglycated cholecystokinin octapeptide (Asp1-glucitol CCK-8) was prepared under hyperglycaemic reducing conditions and purified by reverse phase-high performance liquid chromatography. Electrospray ionisation mass spectrometry and automated Edman degradation demonstrated that CCK-8 was glycated specifically at the amino-terminal Asp1 residue. Effects of Asp1- glucitol CCK-8 and CCK-8 on insulin secretion were examined using glucose- responsive clonal BRIN-BD11 cells. In acute (20 min) incubations, 10-10 mol/l CCK-8 enhanced insulin release by 1.2-1.5-fold at 5.6-11.1 mmol/l glucose. The stimulatory effect induced by 10-10 mol/l CCK-8 was abolished following glycation. At 5.6 mmol/l glucose, CCK-8 at concentrations ranging from 10-11 to 10-7 mol/l induced a significant 1.6-1.9-fold increase in insulin secretion. Insulin output in the presence of Asp1-glucitol CCK-8 over the concentration range 10-11-10-7 mol/l was decreased by 21-35% compared with CCK-8, and its insulinotropic action was effectively abolished. Asp1-glucitol CCK-8 at 10-8 mol/l also completely blocked the stimulatory effects of 10-11-10-8 mol/l CCK-8. These data indicate that structural modification by glycation at the amino-terminal Asp1 residue effectively abolishes and/or antagonises the insulinotropic activity of CCK-8.",

keywords = "BRIN-BD11 cell, Cholecystokinin-8, Glycation, Insulin secretion",

author = "Abdel-Wahab, {Yasser H.A.} and O'Harte, {Finbarr P.M.} and Mooney, {Mark H.} and Conlon, {J. Michael} and Flatt, {Peter R.}",

note = "Funding Information: These studies were supported by Northern Ireland Developmental Research Funding (NIdevR).",

year = "1999",

month = oct,

day = "13",

doi = "10.1016/S0167-4889(99)00108-1",

language = "English",

volume = "1452",

pages = "60--67",

journal = "Biochimica et Biophysica Acta - Molecular Cell Research",

issn = "0167-4889",

publisher = "Elsevier B.V.",

number = "1",

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TY - JOUR

T1 - N-terminal glycation of cholecystokinin-8 abolishes its insulinotropic action on clonal pancreatic B-cells

AU - Abdel-Wahab, Yasser H.A.

AU - O'Harte, Finbarr P.M.

AU - Mooney, Mark H.

AU - Conlon, J. Michael

AU - Flatt, Peter R.

N1 - Funding Information: These studies were supported by Northern Ireland Developmental Research Funding (NIdevR).

PY - 1999/10/13

Y1 - 1999/10/13

N2 - Monoglycated cholecystokinin octapeptide (Asp1-glucitol CCK-8) was prepared under hyperglycaemic reducing conditions and purified by reverse phase-high performance liquid chromatography. Electrospray ionisation mass spectrometry and automated Edman degradation demonstrated that CCK-8 was glycated specifically at the amino-terminal Asp1 residue. Effects of Asp1- glucitol CCK-8 and CCK-8 on insulin secretion were examined using glucose- responsive clonal BRIN-BD11 cells. In acute (20 min) incubations, 10-10 mol/l CCK-8 enhanced insulin release by 1.2-1.5-fold at 5.6-11.1 mmol/l glucose. The stimulatory effect induced by 10-10 mol/l CCK-8 was abolished following glycation. At 5.6 mmol/l glucose, CCK-8 at concentrations ranging from 10-11 to 10-7 mol/l induced a significant 1.6-1.9-fold increase in insulin secretion. Insulin output in the presence of Asp1-glucitol CCK-8 over the concentration range 10-11-10-7 mol/l was decreased by 21-35% compared with CCK-8, and its insulinotropic action was effectively abolished. Asp1-glucitol CCK-8 at 10-8 mol/l also completely blocked the stimulatory effects of 10-11-10-8 mol/l CCK-8. These data indicate that structural modification by glycation at the amino-terminal Asp1 residue effectively abolishes and/or antagonises the insulinotropic activity of CCK-8.

AB - Monoglycated cholecystokinin octapeptide (Asp1-glucitol CCK-8) was prepared under hyperglycaemic reducing conditions and purified by reverse phase-high performance liquid chromatography. Electrospray ionisation mass spectrometry and automated Edman degradation demonstrated that CCK-8 was glycated specifically at the amino-terminal Asp1 residue. Effects of Asp1- glucitol CCK-8 and CCK-8 on insulin secretion were examined using glucose- responsive clonal BRIN-BD11 cells. In acute (20 min) incubations, 10-10 mol/l CCK-8 enhanced insulin release by 1.2-1.5-fold at 5.6-11.1 mmol/l glucose. The stimulatory effect induced by 10-10 mol/l CCK-8 was abolished following glycation. At 5.6 mmol/l glucose, CCK-8 at concentrations ranging from 10-11 to 10-7 mol/l induced a significant 1.6-1.9-fold increase in insulin secretion. Insulin output in the presence of Asp1-glucitol CCK-8 over the concentration range 10-11-10-7 mol/l was decreased by 21-35% compared with CCK-8, and its insulinotropic action was effectively abolished. Asp1-glucitol CCK-8 at 10-8 mol/l also completely blocked the stimulatory effects of 10-11-10-8 mol/l CCK-8. These data indicate that structural modification by glycation at the amino-terminal Asp1 residue effectively abolishes and/or antagonises the insulinotropic activity of CCK-8.

KW - BRIN-BD11 cell

KW - Cholecystokinin-8

KW - Glycation

KW - Insulin secretion

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U2 - 10.1016/S0167-4889(99)00108-1

DO - 10.1016/S0167-4889(99)00108-1

M3 - Article

C2 - 10525160

AN - SCOPUS:0032881940

SN - 0167-4889

VL - 1452

SP - 60

EP - 67

JO - Biochimica et Biophysica Acta - Molecular Cell Research

JF - Biochimica et Biophysica Acta - Molecular Cell Research

IS - 1

ER -

N-terminal glycation of cholecystokinin-8 abolishes its insulinotropic action on clonal pancreatic B-cells

Abstract

Keywords

ASJC Scopus subject areas

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