| First Author | Solloway MJ | Year | 2015 |
| Journal | Cell Rep | Volume | 12 |
| Issue | 3 | Pages | 495-510 |
| PubMed ID | 26166562 | Mgi Jnum | J:224840 |
| Mgi Id | MGI:5689195 | Doi | 10.1016/j.celrep.2015.06.034 |
| Citation | Solloway MJ, et al. (2015) Glucagon Couples Hepatic Amino Acid Catabolism to mTOR-Dependent Regulation of alpha-Cell Mass. Cell Rep 12(3):495-510 |
| abstractText | Understanding the regulation of islet cell mass has important implications for the discovery of regenerative therapies for diabetes. The liver plays a central role in metabolism and the regulation of endocrine cell number, but liver-derived factors that regulate alpha-cell and beta-cell mass remain unidentified. We propose a nutrient-sensing circuit between liver and pancreas in which glucagon-dependent control of hepatic amino acid metabolism regulates alpha-cell mass. We found that glucagon receptor inhibition reduced hepatic amino acid catabolism, increased serum amino acids, and induced alpha-cell proliferation in an mTOR-dependent manner. In addition, mTOR inhibition blocked amino-acid-dependent alpha-cell replication ex vivo and enabled conversion of alpha-cells into beta-like cells in vivo. Serum amino acids and alpha-cell proliferation were increased in neonatal mice but fell throughout postnatal development in a glucagon-dependent manner. These data reveal that amino acids act as sensors of glucagon signaling and can function as growth factors that increase alpha-cell proliferation. |
