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 journalArticlepeer-review

13 Citations (Scopus)


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 languageEnglish
Pages (from-to)60-67
Number of pages8
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Issue number1
Publication statusPublished - Oct 13 1999
Externally publishedYes


  • BRIN-BD11 cell
  • Cholecystokinin-8
  • Glycation
  • Insulin secretion

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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