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Glycated cholecystokinin-8 has an enhanced satiating activity and is protected against enzymatic degradation

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O'Harte, Finbarr, Mooney, MH, Kelly, CMN and Flatt, Peter (1998) Glycated cholecystokinin-8 has an enhanced satiating activity and is protected against enzymatic degradation. DIABETES, 47 (10). pp. 1619-1624. [Journal article]

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Monoglycated cholecystokinin octapeptide (CCK-8) (glucitol-Asp(1) adduct) modified at the NH2-terminus was prepared under hyperglycemic conditions, purified by high-performance liquid chromatography, and characterized by mass spectrometry (M-r 1228.4 Da) and peptide sequencing. CCK-8 (100 nmol/kg, i.p.) significantly (P < 0.001) reduced voluntary food intake of fasted mice for up to 30 min after its administration, compared with saline-administered controls. Glycated CCK-8 reduced food intake at 30-120 min (P <0.01 to P < 0.001) and significantly reduced feeding compared with CCK-8 from 60 to 120 min (P < 0.01). In vitro plasma degradation studies indicated that glycated CCK-8 was resistant to the normal rapid enzymatic conversion to CCK fragments. This study demonstrated that CCK-8 is a potent short-term inhibitor of food intake, and that structural modification of this peptide by amino-terminal glycation leads to enhanced satiating activity, partially due to increased resistance to serum aminopeptidase degradation.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Diabetes
ID Code:3127
Deposited By:Professor Peter Flatt
Deposited On:08 Jan 2010 14:32
Last Modified:11 Jun 2010 13:09

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