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Glucagon in NASH/NAFLD

It is well known that glucagon acts on the liver to stimulate glycogenolysis and gluconeogenesis. But research also suggests an “important role for the liver in the regulation of glucagon secretion”1. Furthermore, scientists have found “fasting hyperglucagonemia in NAFLD patients, independently of type 2 diabetes”2. They propose that “NAFLD, and not type 2 diabetes, causes high fasting glucagon levels and that liver damage is central to hyperglucagonaemia”1.



Amino acid metabolism is altered in NAFLD and glutamate is the amino acid with the strongest association with severity of fibrosis. Interestingly, glutamate has been shown to stimulate glucagon release.3 This may shed light on one of the mechanisms by which the liver regulates glucagon secretion in the overlapping conditions of NAFLD, obesity and type 2 diabetes.


  1. Junker AE et al. (2016) J Intern Med. 279:485-493.
  2. Junker AE (2017) Dan Med J. 64:B5363.
  3. Cabrera O et al. (2008) Cell Metab 7:545-554.