| First Author | Hoizumi M | Year | 2019 |
| Journal | Biochem Biophys Res Commun | Volume | 513 |
| Issue | 4 | Pages | 974-982 |
| PubMed ID | 31003779 | Mgi Jnum | J:291658 |
| Mgi Id | MGI:6443089 | Doi | 10.1016/j.bbrc.2019.04.036 |
| Citation | Hoizumi M, et al. (2019) Inhibition of GIP signaling extends lifespan without caloric restriction. Biochem Biophys Res Commun 513(4):974-982 |
| abstractText | AIMS/INTRODUCTION: Caloric restriction (CR) promotes longevity and exerts anti-aging effects by increasing Sirtuin production and activation. Gastric inhibitory polypeptide (GIP), a gastrointestinal peptide hormone, exerts various effects on pancreatic beta-cells and extra-pancreatic tissues. GIP promotes glucose-dependent augmentation of insulin secretion and uptake of nutrients into the adipose tissue. MATERIALS AND METHODS: Gipr(-/-) and Gipr(+/+) mice were used for lifespan analysis, behavior experiments and gene expression of adipose tissue and muscles. 3T3-L1 differentiated adipocytes were used for Sirt1 and Nampt expression followed by treatment with GIP and alpha-lipoic acid. RESULTS: We observed that GIP receptor-knockout (Gipr(-/-)) mice fed normal diet showed an extended lifespan, increased exploratory and decreased anxiety-based behaviors, which are characteristic behavioral changes under CR. Moreover, Gipr(-/-) mice showed increased Sirt1 and Nampt expression in the adipose tissue. GIP suppressed alpha-lipoic acid-induced Sirt1 expression and activity in differentiated adipocytes. CONCLUSIONS: Although maintenance of CR is difficult, food intake and muscle endurance of Gipr(-/-) mice were similar to those of wild-type mice. Inhibition of GIP signaling may be a novel strategy to extend the lifespan of diabetic patients. |
