Details

Autor(en) / Beteiligte

• Solloway, Mark J.
• Madjidi, Azadeh
• Gu, Chunyan
• Eastham-Anderson, Jeff
• Clarke, Holly J.
• Kljavin, Noelyn
• Zavala-Solorio, Jose
• Kates, Lance
• Friedman, Brad
• Brauer, Matt
• Wang, Jianyong
• Fiehn, Oliver
• Kolumam, Ganesh
• Stern, Howard
• Lowe, John B.
• Peterson, Andrew S.
• Allan, Bernard B.

Titel

Glucagon Couples Hepatic Amino Acid Catabolism to mTOR-Dependent Regulation of α-Cell Mass

Ist Teil von

• Cell reports (Cambridge), 2015-07, Vol.12 (3), p.495-510

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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 α-cell and β-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 α-cell mass. We found that glucagon receptor inhibition reduced hepatic amino acid catabolism, increased serum amino acids, and induced α-cell proliferation in an mTOR-dependent manner. In addition, mTOR inhibition blocked amino-acid-dependent α-cell replication ex vivo and enabled conversion of α-cells into β-like cells in vivo. Serum amino acids and α-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 α-cell proliferation. [Display omitted] •Glucagon regulates hepatic amino acid catabolism and serum amino acid levels•mTOR activity is required for α-cell proliferation after glucagon receptor inhibition•Amino acids promote α-cell proliferation ex vivo in an mTOR-dependent manner•mTOR determines α-cell fate Here, Solloway et al. propose a nutrient-sensing circuit between liver and pancreas in which glucagon-dependent clearance of amino acids is coupled to α-cell mass. Acting as sensors, amino acids relay the degree of hepatic glucagon signaling to islets and promote mTOR-dependent α-cell proliferation.