The Peter Attia Drive A masterclass on insulin resistance—mechanisms and implications | Gerald Shulman, M.D., Ph.D. (#140 rebroadcast)
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Nov 21, 2022 
Gerald Shulman, a Yale Professor and Director of the Diabetes Research Center, shares his expertise on insulin resistance and its implications for health. He dives into mechanisms affecting muscle and liver function, the evolutionary role of insulin resistance, and how lifestyle factors like diet and exercise play a significant part. Shulman also highlights the effectiveness of Metformin, linking its action to longevity, while explaining the alarming connections between lipid accumulation and metabolic health.
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Intralipid and Insulin Resistance
- Intralipid infusion can induce insulin resistance in healthy individuals within hours.
- This suggests that elevated fatty acids impair insulin-stimulated glucose transport.
Challenging Randle's Hypothesis
- Philip Randle's rat studies suggested that fatty acids cause insulin resistance by inhibiting glycolysis.
- Shulman’s human studies contradicted this, showing impaired glucose transport, not glycolysis inhibition.
DAG and Insulin Resistance
- Diacylglycerol (DAG), not triglyceride, is the culprit in lipid-induced insulin resistance.
- DAG activates novel PKCs, which inhibit insulin signaling and glucose transport.