The liver-alpha cell axis and type 2 diabetes.

The liver-alpha cell axis and type 2 diabetes. Endocr Rev. 2019 Mar 28;: Authors: Wewer Albrechtsen NJ, Pedersen J, Galsgaard KD, Winther-Sørensen M, Suppli MP, Janah L, Gromada J, Vilstrup H, Knop FK, Holst JJ Abstract Both type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) strongly associate with increasing body mass index (BMI) and together these metabolic diseases affect millions of individuals. In patients with T2D, increased secretion of glucagon (hyperglucagonemia) contributes to the diabetic hyperglycemia as proven by the significant lowering of fasting plasma glucose levels following glucagon receptor antagonist (GRA) administration. Emerging data now indicate that the elevated plasma concentrations of glucagon may also be associated with hepatic steatosis and not necessarily with the presence or absence of T2D. Thus, fatty liver disease, most often secondary to overeating, may result in impaired amino acid turnover, leading to increased plasma concentrations of certain glucagonotropic amino acids (e.g. alanine). This, in turn, causes increased glucagon secretion which may help to restore amino acid turnover and ureagenesis, but may eventually also led to increased hepatic glucose production, a hallmark of T2D. Early experimental findings support the hypothesis that hepatic steatosis impairs glucagon's actions on amino acid turnover and ureagenesis. Hepatic steatosis also impairs hepatic insulin sensitivity...
Source: Endocrine Reviews - Category: Endocrinology Tags: Endocr Rev Source Type: research