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Horm Metab Res 2013; 45(06): 471-473
DOI: 10.1055/s-0032-1331767
Short Communication
© Georg Thieme Verlag KG Stuttgart · New York

Beneficial Effects of (pGlu-Gln)-CCK-8 on Energy Intake and Metabolism in High Fat Fed Mice are Associated with Alterations of Hypothalamic Gene Expression

I. A. Montgomery
1   SAAD Centre for Pharmacy and Diabetes, University of Ulster, Coleraine, Northern Ireland, UK
,
N. Irwin
1   SAAD Centre for Pharmacy and Diabetes, University of Ulster, Coleraine, Northern Ireland, UK
,
P. R. Flatt
1   SAAD Centre for Pharmacy and Diabetes, University of Ulster, Coleraine, Northern Ireland, UK
› Author Affiliations
Further Information

Publication History

received 08 October 2012

accepted 03 December 2012

Publication Date:
11 January 2013 (online)

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Abstract

Cholecystokinin (CCK) is a gastrointestinal hormone with potential therapeutic promise for obesity-diabetes. The present study examined the effects of twice daily administration of the N-terminally modified stable CCK-8 analogue, (pGlu-Gln)-CCK-8, on metabolic control and hypothalamic gene expression in high fat fed mice. Sub-chronic twice daily injection of (pGlu-Gln)-CCK-8 for 16 days significantly decreased body weight (p<0.05), energy intake (p<0.01), circulating blood glucose (p<0.001), and plasma insulin (p<0.001) compared to high fat controls. Furthermore, (pGlu-Gln)-CCK-8 markedly improved glucose tolerance (p<0.05) and insulin sensitivity (p<0.05). Assessment of hypothalamic gene expression on day 16 revealed significantly elevated NPY (p<0.05) and reduced POMC (p<0.05) and MC4R (p<0.05) mRNA expression in (pGlu-Gln)-CCK-8 treated mice. High fat feeding or (pGlu-Gln)-CCK-8 treatment had no significant effects on hypothalamic gene expression of receptors for leptin, CCK1 and GLP-1. These studies underscore the potential of (pGlu-Gln)-CCK-8 for the treatment of obesity-diabetes and suggest modulation of NPY and melanocortin related pathways may be involved in the observed beneficial effects.

 

  • References

  • 1 Rehfeld JF. Acta Physiol (Oxf) 2011; 201: 405-411
    CrossrefPubMed
  • 2 Ritter RC, Covasa M, Matson CA. Neuropeptides 1999; 33: 387-399
    CrossrefPubMed
  • 3 Irwin N, Frizelle P, Montgomery IA, Moffett RC, O’Harte FPM, Flatt PR. Diabetologia 2012; 55: 2747-2758
    CrossrefPubMed
  • 4 Irwin N, Montgomery IA, O’Harte FPM, Frizelle P, Flatt PR Int J Obesity 2012 Nov 20 [Epub ahead of print]
    PubMed
  • 5 Bi S, Scott KA, Hyun J, Ladenheim EE, Moran TH. Endocrinol 2005; 146: 1676-1685
    CrossrefPubMed
  • 6 Moran TH, Bi S. Philos Trans R Soc Lond B Biol Sci 2006; 361: 1211-1218
    PubMed
  • 7 Millington GW. Nutr Metab (Lond) 2007; 4: 18
    CrossrefPubMed
  • 8 Fan W, Ellacott KL, Halatchev IG, Takahashi K, Yu P, Cone RD. Nat Neurosci 2004; 7: 335-336
    CrossrefPubMed
  • 9 Hisadome K, Reimann F, Gribble FM, Trapp S. Diabetes 2011; 60: 2701-2709
    CrossrefPubMed
  • 10 Merino B, Cano V, Guzmán R, Somoza B, Ruiz-Gayo M. Endocrinol 2008; 149: 1994-2000
    CrossrefPubMed