Research
Hormonal
In the liver, increased diacylglycerol activates PKC-epsilon, which reduces IRS-2 tyrosine phosphorylation, leading to decreased glycogen synthase activation and increased gluconeogenesis, causing hepatic insulin resistance.
Hepatic insulin resistance is driven by lipid intermediates (DAG) interfering with liver insulin signaling, leading to excessive glucose production. Managing liver fat can improve this.
GoodSupportsHIGH confidence
increases in hepatocellular diacylglycerol content activate protein kinase C-epsilon, leading to reduced insulin-stimulated tyrosine phosphorylation of IRS-2.
Why this rating
Based on studies in rodents and humans using MRS and molecular analysis.
Source
Molecular Mechanisms of Insulin Resistance in Humans and Their Potential Links With Mitochondrial Dysfunction
Katsutaro Morino et al. · Diabetes · 2006
DOI 10.2337/db06-s002
narrative_reviewCited 856×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
More from this paper
- Increased intramyocellular lipid metabolites (fatty acyl CoAs and diacylglycerol) activate serine/threonine kinase cascades (e.g., PKC-theta), which phosphorylate IRS-1 on serine residues, thereby inhibiting insulin-stimulated glucose transport and causing skeletal muscle insulin resistance.Good
- Reduced mitochondrial density and function predispose individuals to intramyocellular lipid accumulation, which subsequently leads to insulin resistance.Good
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