#140

Gerald Shulman is a Professor of Medicine, Cellular & Molecular Physiology, and the Director of the Diabetes Research Center at Yale. His pioneering work on the use of advanced technologies to analyze metabolic flux within cells has greatly contributed to the understanding of insulin resistance and type 2 diabetes. In this episode, Gerald clarifies what insulin resistance means as it relates to the muscle and the liver, and the evolutionary reason for its existence. He goes into depth on mechanisms that lead to and resolve insulin resistance, like the role of diet, exercise, and pharmacological agents. As a bonus, Gerald concludes with insights into Metformin’s mechanism of action and its suitability as a longevity agent.

We discuss:
00:00:00 - Intro
00:04:30 - Gerald’s background and interest in metabolism and insulin resistance
00:08:30 - Insulin resistance as a root cause of chronic disease
00:12:00 - How Gerald uses NMR to see inside cells
00:19:15 - Defining and diagnosing insulin resistance and type 2 diabetes
00:31:15 - The role of lipids in insulin resistance
00:40:15 - Confirmation of glucose transport as the root problem in lipid-induced insulin resistance
00:50:00 - The role of exercise in protecting against insulin resistance and fatty liver (50:00);
-Insulin resistance in the liver
01:17:15 - The evolutionary explanation for insulin resistance—an important tool for surviving starvation
01:22:30 - The critical role of gluconeogenesis, and how it’s regulated by insulin
01:32:15 - Inflammation and body fat as contributing factors to insulin resistance
01:41:15 - Treatment approaches for fatty liver and insulin resistance, and an exciting new pharmacological approach
01:58:15 - Metformin’s mechanism of action and its suitability as a longevity agent

Show notes page: https://peterattiamd.com/geraldshulman/

About:
The Peter Attia Drive is a weekly, ultra-deep-dive podcast focusing on maximizing health, longevity, critical thinking…and a few other things. With over 30 million episodes downloaded, it features topics including fasting, ketosis, Alzheimer’s disease, cancer, mental health, and much more.

Peter is a physician focusing on the applied science of longevity. His practice deals extensively with nutritional interventions, exercise physiology, sleep physiology, emotional and mental health, and pharmacology to increase lifespan (delay the onset of chronic disease), while simultaneously improving healthspan (quality of life).

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