GLYCATED CHOLECYSTOKININ-8 HAS AN ENHANCED SATIATING ACTIVITY AND IS PROTECTED AGAINST ENZYMATIC DEGRADATION

Monoglycated cholecystokinin octapeptide (CCK-8) (glucitol-Asp(1) addu ct) modified at the NH2-terminus was prepared under hyperglycemic cond itions, purified by high-performance liquid chromatography, and charac terized by mass spectrometry (M-r 1228.4 Da) and peptide sequencing. C CK-8 (100 nmol/kg, i.p.) significantly (P < 0.001) reduced voluntary f ood intake of fasted mice for up to 30 min after its administration, c ompared with saline-administered controls. Glycated CCK-8 reduced food intake at 30-120 min (P < 0.01 to P < 0.001) and significantly reduce d 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 inta ke, and that structural modification of this peptide by amino-terminal glycation leads to enhanced satiating activity, partially due to incr eased resistance to serum aminopeptidase degradation.