Mechanisms of Insulin Action and Insulin Resistance.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing mechanistic and physiological literature without original human trial data or systematic review methodology.
PubMed 30067154 · doi:10.1152/physrev.00063.2017
What was done
This narrative review synthesized the physiological mechanisms of normal insulin action and the pathophysiology of insulin resistance across skeletal muscle, liver, and white adipose tissue. The authors evaluated cell-autonomous receptor signaling, inter-tissue crosstalk (particularly adipose lipolysis and hepatic gluconeogenesis), candidate mediators (bioactive lipids such as diacylglycerols, ceramides, acylcarnitines; ER and mitochondrial nutrient stress; inflammatory factors; branched-chain amino acids; and organokines), and framed an integrated model for selective hepatic insulin resistance and type 2 diabetes pathogenesis.
What was found
The abstract reports no numerical data, effect sizes, or quantitative statistical results. It outlines an integrated mechanistic framework proposing that diverse cellular stresses and molecular mediators converge on ectopic lipid accumulation and metabolite-driven gluconeogenesis to produce whole-body insulin resistance.
Why it matters
It unifies disparate molecular and physiological findings into a single framework across multiple organ systems, helping guide mechanistic research and rational drug development for type 2 diabetes.
Limits
As a narrative review, it lacks systematic search criteria, quality scoring of included studies, and quantitative meta-analytic pooling. It presents mechanistic synthesis and theory rather than new clinical or experimental data.
Cited by
- contradicts Insulin resistance is caused by a receptor shutdown driven by excessive insulin stimulation from high carbohydrate intake or frequent eating.