Sign up to receive Peter's email newsletter: https://bit.ly/4c602k2 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). Learn more: https://peterattiamd.com/ Subscribe to receive exclusive subscriber-only content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Connect with Peter on: Facebook: http://bit.ly/PeterAttiaMDFB Twitter: http://bit.ly/PeterAttiaMDTW Instagram: http://bit.ly/PeterAttiaMDIG Subscribe to The Drive: Apple Podcast: http://bit.ly/TheDriveApplePodcasts Overcast: http://bit.ly/TheDriveOvercast Spotify: http://bit.ly/TheDriveSpotify Google Play: http://bit.ly/TheDriveGooglePlay