Elevated liver fat content disrupts the liver-α cell axis

Elevated liver fat content disrupts the liver-α cell axis

by | Jun 16, 2021 | Literature, Cardiometabolic disease, Hepatology

The liver–alpha cell axis associates with liver fat and insulin resistance: a validation study in women with non-steatotic liver fat levels

Elevated liver fat content is a hallmark of metabolic syndrome. This causes impaired glucagon sensitivity of liver cells and in turn increased plasma levels of amino acids. As consequence, α-cells secrete glucagon release by α-cells is fostered. Hyperglucagonaemia can lead to the development of type 2 diabetes (T2D) due to steady hepatic glucose production. This regulatory circuit is described by the liver-α cell axis. This study examined the association of liver fat content and insulin resistance with the glucagon-alanine index, which is an indicator for the integrity of the liver-α cell axis.


The study, led by Dr Andreas Lechner from Helmholtz Zentrum Munich, is based on data from 79 young women with low levels of liver fat, participating in the Prediction, Prevention and Subclassification of Type 2 Diabetes (PPSDiab) study. Their glucagon-alanine index was calculated and analyzed for an association with liver fat content and inulin resistance.


The results revealed a significant correlation between liver fat and the glucagon-alanine index from a liver fat level of 0.5%, independent of insulin resistance. The correlation between the glucagon-index and insulin resistance also started around 0.5% liver fat content. However, this association was not independent of liver fat content in participants with > 0.5% liver fat content. These results indicate an impairment of the liver-α cell axis already at non-steatotic liver fat levels.


In summary, findings suggest an association of liver fat content and glucagon-alanine index that’s independent of insulin resistance. A disturbed regulatory circuit of liver and α-cells leads to hyperglucagonaemia and might foster the development of T2D. Therefore, the glucagon-alanine index might have potential as predictive biomarker.

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Gar C, Haschka SJ, Kern-Matschilles S, Rauch B, Sacco V, Prehn C et al.: The liver-alpha cell axis associates with liver fat and insulin resistance: a validation study in women with non-steatotic liver fat levels. (2021) Diabetologia | https://doi.org/s00125-020-05334-x

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