# Hepatic insulin resistance

Hepatic insulin resistance means your liver stops listening to insulin's 'stop making sugar' signal after meals, even though it still obeys insulin's 'make fat' signal. Scientists call this odd split selective hepatic insulin resistance. The result: your liver keeps dumping glucose into your blood when it should not, so your body pumps out extra insulin to compensate (hyperinsulinemia), which in turn drives more fat production and high blood triglycerides. What causes it? Mainly fat building up inside the liver, from too many free fatty acids flooding in, from fructose, and from a weakened ability to burn fat in the mitochondria. These all converge on a faulty switch in the insulin signal (serine phosphorylation of IRS-1 and IRS-2). This is one of the earliest and most central problems in fatty liver disease (now called MASLD) and type 2 diabetes, and it tracks with higher risk of heart disease and earlier death.

## Sources

- Petersen MC, Vatner DF, Shulman GI. (2017). Regulation of Hepatic Glucose Metabolism in Health and Disease. Nature Reviews Endocrinology. https://doi.org/10.1038/nrendo.2017.80
- Titchenell PM, Lazar MA, Birnbaum MJ. (2017). Unraveling the Regulation of Hepatic Metabolism by Insulin. Trends in Endocrinology and Metabolism. https://doi.org/10.1016/j.tem.2017.03.003

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