| First Author | Li Z | Year | 2013 |
| Journal | Diabetes | Volume | 62 |
| Issue | 7 | Pages | 2359-67 |
| PubMed ID | 23423572 | Mgi Jnum | J:208547 |
| Mgi Id | MGI:5563697 | Doi | 10.2337/db12-0901 |
| Citation | Li Z, et al. (2013) Developmental role for endocannabinoid signaling in regulating glucose metabolism and growth. Diabetes 62(7):2359-67 |
| abstractText | Treatment of ob/ob (obese) mice with a cannabinoid receptor 1 (Cnr1) antagonist reduces food intake, suggesting a role for endocannabinoid signaling in leptin action. We further evaluated the role of endocannabinoid signaling by analyzing the phenotype of Cnr1 knockout ob/ob mice. Double mutant animals show a more severe growth retardation than ob/ob mice with similar levels of adiposity and reduced IGF-I levels without alterations of growth hormone (GH) levels. The double mutant mice are also significantly more glucose intolerant than ob/ob mice. This is in contrast to treatment of ob/ob mice with a Cnr1 antagonist that had no effect on glucose metabolism, suggesting a possible requirement for endocannabinoid signaling during development for normal glucose homeostasis. Double mutant animals also showed similar leptin sensitivity as ob/ob mice, suggesting that there are developmental changes that compensate for the loss of Cnr1 signaling. These data establish a role for Cnr1 during development and suggest that compensatory changes during development may mitigate the requirement for Cnr1 in mediating the effects of leptin. The data also suggest a developmental role for Cnr1 to promote growth, regulate the GH/IGF-I axis, and improve beta-cell function and glucose homeostasis in the setting of leptin deficiency. |
