Metabolic effects of activation of CCK receptor signaling pathways by twice-daily administration of the enzyme-resistant CCK-8 analog, (pGlu-Gln)-CCK-8, in normal mice.
Cholecystokinin (CCK) is a hormone that has important physiological effects on energy balance. This study has used a stable CCK(1) receptor agonist, (pGlu-Gln)-CCK-8, to evaluate the metabolic effects of prolonged administration in normal mice. Twice-daily injection of (pGlu-Gln)-CCK-8 for 28 days resulted in significantly lowered body weights (P<0.05) on days 24 and 28, which was associated with decreased accumulated calorie intake (P<0.01) from day 12 onward. Nonfasting plasma glucose was significantly reduced (P<0.05) on day 28, while plasma insulin concentrations were increased (P<0.05). After 28 days, glucose tolerance and glucose-mediated insulin secretion were not significantly different in (pGlu-Gln)-CCK-8-treated mice. However, following a 15-min refeeding period in 18-h fasted mice, glucose levels were significantly (P<0.05) decreased by (pGlu-Gln)-CCK-8 despite similar food intake and nutrient-induced insulin levels. Insulin sensitivity in (pGlu-Gln)-CCK-8-treated mice was significantly (P<0.01) improved compared with controls. Accumulation of triacylglycerol in liver was reduced (P<0.01) but there were no differences in circulating cholesterol and triacylglycerol concentrations, as well as triacylglycerol content of pancreatic, muscle, and adipose tissue in (pGlu-Gln)-CCK-8 mice. These data highlight the beneficial metabolic effects of prolonged (pGlu-Gln)-CCK-8 administration and confirm a lack of detrimental effects.
School of Biomedical Sciences, The SAAD Centre for Pharmacy and Diabetes, University of Ulster, Coleraine, Northern Ireland, UK. n.irwin@ulster.ac.uk
Nigel
N
Irwin
Pamela
P
Frizelle
Finbarr P M
FP
O'Harte
Peter R
PR
Flatt
D000818:Animals; D019440:Anti-Obesity Agents / Q000009:adverse effects / Q000494:pharmacology*; D001786:Blood Glucose / Q000032:analysis; D002149:Energy Intake / Q000187:drug effects; D006943:Hyperglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D019518:Postprandial Period; D043886:Receptor, Cholecystokinin A / Q000819:agonists*; D015398:Signal Transduction / Q000187:drug effects*; D012844:Sincalide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects
C578541:(pGlu-Gln)-CCK-8; D019440:Anti-Obesity Agents; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D043886:Receptor, Cholecystokinin A; D014280:Triglycerides; D012844:Sincalide