Research
Hormonal
Hepatic insulin resistance is characterized by a 'selective' defect where insulin fails to suppress gluconeogenesis but continues to stimulate de novo lipogenesis, driven by substrate flux (fatty acids and glucose) rather than insulin signaling alone.
In T2D, the liver ignores insulin's command to stop making glucose, but still responds to high sugar/fat intake by making more fat. Managing carbohydrate and fat intake is critical to reducing liver fat and glucose production.
StrongQualifiesHIGH confidence
The major source of hepatic lipid synthesis, esterification of preformed fatty acids, is primarily dependent on substrate delivery and largely independent of hepatic insulin action.
Why this rating
Supported by rat studies, antisense oligonucleotide treatments, and human metabolic studies.
Source
The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux
Varman T. Samuel et al. · Journal of Clinical Investigation · 2016
DOI 10.1172/jci77812
narrative_reviewCited 1,398×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
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