The VIP/VPAC1R Pathway Regulates Energy and Glucose Homeostasis by Modulating GLP-1, Glucagon, Leptin and PYY Levels in Mice

Biology

Michael Lewis¹  Joseph R. Pisegna²  Daniel Sanford³  Suwan Oh³  Arielle Gabalski³  Leon Luong³  Patrizia Germano³  John P. Vu³ 

[1] Department of Pathology, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA;Digestive Diseases Research Center (CURE), Department of Medicine, University of California, Los Angeles, CA 90073, USA;Research Service, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA;

关键词: VPAC1R;    VIP;    calorimetry;    glucose;    GLP-1;    glucagon;   

DOI  :  10.3390/biology11030431

来源: DOAJ

【 摘 要 】

Vasoactive Intestinal Peptide binds with high affinity to VPAC1R and VPAC2R, thus regulating key physiologic functions. Previously, we documented in VIP^−/− mice a leaner body phenotype and altered metabolic hormones. Past reports described in VPAC2^−/− mice impaired circadian rhythm, reduced food intake, and altered metabolism. To better define the effects of VPAC1R on body phenotype, energy/glucose homeostasis, and metabolism, we conducted a 12-week study in a VPAC1R null model. Our results reveal that VPAC1^−/− mice experienced significant metabolic alterations during the dark cycle with greater numbers of feeding bouts (p = 0.009), lower Total Energy Expenditure (p = 0.025), VO₂ (p = 0.029), and VCO₂ (p = 0.016); as well as during the light cycle with lower Total Energy Expenditure (p = 0.04), VO₂ (p = 0.044), and VCO₂ (p = 0.029). Furthermore, VPAC1^−/− mice had significantly higher levels of GLP-1 and PYY during fasting, and higher levels of GLP-1, glucagon leptin and PYY during postprandial conditions. In addition, VPAC1^−/− mice had lower levels of glucose at 60′ and 120′, as assessed by insulin tolerance test. In conclusion, this study supports a key role for VPAC1R in the regulation of body glucose/energy homeostasis and metabolism.

【 授权许可】

Unknown