Effect of CCK-8 on pentose phosphate shunt activity, pyridine nucleotides, and glucokinase of rat islets.
In rat pancreatic islets the effects of cholecystokinin octapeptide (CCK-8) on pentose phosphate shunt (PPS) activity, glucokinase and hexokinase activity, and NADPH, NADP+, NADH, and NAD+ were studied. By elevating the glucose concentration from 3.0 to 8.3 and 16.7 mM the oxidation of [1-14C]- and [6-14C]glucose and the calculated PPS activity were increased in a concentration-dependent manner; 10 nM CCK-8 enhanced selectively the effect on [1-14C]glucose oxidation thereby increasing the PPS activity but only at an intermediate glucose concentration (8.3 mM). CCK-8 had no effect on glucokinase or hexokinase activity and CCK-8 did not influence glucose utilization. By elevating the glucose concentration, total NADPH and NADH were increased and total NADP+ and NAD+ were decreased. CCK-8 (10 nM) increased selectively NADPH and decreased NADP+ but did not change NADH or NAD+; the effect of CCK-8 on NADPH and NADH was only observed in the presence of an intermediate stimulatory glucose concentration (8.3 mM) but not at either a substimulatory glucose concentration or a maximally stimulatory glucose concentration for insulin release (3.0 or 16.7 mM). The data indicate first that CCK-8 does not act on glucose phosphorylation or glucose utilization and second that CCK-8 increases PPS activity and NADPH levels in rat pancreatic islets. Since the concentrations of glucose necessary for these CCK-8 effects are in the range of 8.3 mM and parallel with those necessary for insulin release as shown in earlier observations, glucose oxidation via pentose phosphate shunt and NADPH are suggested to be related to the CCK-8-modulated insulin release.
Verspohl
E J
EJ
Department of Pharmacology, University of Tübingen, Federal Republic of Germany.
Breuning
I
I
Ammon
H P
HP
D000818:Animals; D005941:Glucokinase / Q000378:metabolism*; D006593:Hexokinase / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D009243:NAD / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D010084:Oxidation-Reduction; D010427:Pentose Phosphate Pathway / Q000187:drug effects*; D051381:Rats; D012844:Sincalide / Q000494:pharmacology*; D014316:Tritium
D009243:NAD; D014316:Tritium; D009249:NADP; D006593:Hexokinase; D005941:Glucokinase; D012844:Sincalide