| First Author | Okamoto H | Year | 2017 |
| Journal | Proc Natl Acad Sci U S A | Volume | 114 |
| Issue | 10 | Pages | 2747-2752 |
| PubMed ID | 28143927 | Mgi Jnum | J:240929 |
| Mgi Id | MGI:5896848 | Doi | 10.1073/pnas.1620989114 |
| Citation | Okamoto H, et al. (2017) Angptl4 does not control hyperglucagonemia or alpha-cell hyperplasia following glucagon receptor inhibition. Proc Natl Acad Sci U S A 114(10):2747-2752 |
| abstractText | Genetic disruption or pharmacologic inhibition of glucagon signaling effectively lowers blood glucose but results in compensatory glucagon hypersecretion involving expansion of pancreatic alpha-cell mass. Ben-Zvi et al. recently reported that angiopoietin-like protein 4 (Angptl4) links glucagon receptor inhibition to hyperglucagonemia and alpha-cell proliferation [Ben-Zvi et al. (2015) Proc Natl Acad Sci USA 112:15498-15503]. Angptl4 is a secreted protein and inhibitor of lipoprotein lipase-mediated plasma triglyceride clearance. We report that Angptl4-/- mice treated with an anti-glucagon receptor monoclonal antibody undergo elevation of plasma glucagon levels and alpha-cell expansion similar to wild-type mice. Overexpression of Angptl4 in liver of mice caused a 8.6-fold elevation in plasma triglyceride levels, but did not alter plasma glucagon levels or alpha-cell mass. Furthermore, administration of glucagon receptor-blocking antibody to healthy individuals increased plasma glucagon and amino acid levels, but did not change circulating Angptl4 concentration. These data show that Angptl4 does not link glucagon receptor inhibition to compensatory hyperglucagonemia or expansion of alpha-cell mass, and that it cannot be given to induce such secretion and growth. The reduction of plasma triglyceride levels in Angptl4-/- mice and increase following Angptl4 overexpression suggest that changes in plasma triglyceride metabolism do not regulate alpha-cells in the pancreas. Our findings corroborate recent data showing that increased plasma amino acids and their transport into alpha-cells link glucagon receptor blockage to alpha-cell hyperplasia. |
