Is Insulin Really a Response to Blood Glucose? | Mastering Nutrition #36

Insulin is almost universally considered a hormone whose primary purpose is to regulate blood glucose levels. Indeed, it does this. But is that the whole picture? When we look at what governs pancreatic insulin secretion inside the beta-cell, it's about total energy and the versatility of the short-term energy supply, not about glucose. When we look at what insulin does to energy metabolism, it does far more than regulate blood glucose: it governs how we use energy and what we do with it. What is insulin really doing? Find out in this episode. I can't promise the episode is practical, but I promise it's incredibly thought-provoking. You can find the show notes at chrismasterjohnphd.com/45. This episode is brought to you by Ample Meal. Ample is a meal-in-a-bottle that takes a total of two minutes to prepare, consume, and clean up. It provides a balance of fat, protein, and carbohydrate, plus all the vitamins and minerals you need in a single meal, all from a blend of natural ingredients. The protein is from whey and collagen. The fat is from coconut oil and macadamia nut oil. The carbohydrates, vitamins, and minerals come exclusively from food sources like sweet potatoes, bananas, cocoa powder, wheat and barley grass, and chlorella. I use Ample on Mondays when I have 12 hours of appointments with breaks no longer than 15 minutes. It keeps my brain going while I power through the long day, never letting food prep make me late for an appointment. Head to amplemeal.com and enter the promo code "CHRIS15" at checkout for a 15% discount off your first order. This episode is brought to you by US Wellness Meats. I use their liverwurst as a convenient way to make a sustainable habit of eating a diversity of organ meats. They also have a milder braunschweiger and an even milder head cheese that gives you similar benefits, as well as a wide array of other meat products, all from animals raised on pasture. Head to grasslandbeef.com and enter promo code "Chris" at checkout to get a 15% discount on any order that is at least 7 pounds and is at least $75 after applying the discount but under 40 pounds (it can be 39.99 lbs, but not 40). You can use this discount code not once, but twice! Here's what you'll find in this episode, and more: 00:55 Cliff Notes 12:45 Insulin is widely perceived as a response to blood glucose, yet there are a variety of reasons to see it as a response to short-term energy status and the versatility of that short-term energy. 14:48 Defining "insulin signaling." 18:00 Dietary effects on insulin and glucagon: fat, protein, and carbohydrate. 21:45 Effects of insulin outside of energy metabolism: for example, glutathione synthesis, production and activation of thyroid hormone, protection against glycation. 28:10 Insulin signaling is directly triggered by the level of ATP in the pancreatic beta-cell. 35:10 Amplification signals in beta-cell: anaplerosis, cataplerosis, lipogenesis, and the pentose phosphate pathway. 45:30 The anatomy and physiology of macronutrient transport mean that fat and carbohydrate are delivered to the pancreatic beta-cell in very different ways, resulting from circulatory routes and the relative expression of glucose transporters and lipoprotein lipase. 01:07:15 Unique roles of glucose in specialized energetic pathways. 01:07:50 Cytosolic ATP generation depends on glucose and is important to red blood cells, astrocytes, the lens and cornea of the eye, the kidney medulla, the testes, and under conditions of high-intensity exercise, stress, hypoxia, or suffocation. 01:11:10 Only glucose can allow a tissue to borrow energy from the liver in the Cori cycle. 01:14:30 Glucose is the primary anaplerotic substrate; protein is secondary; fat has little anaplerotic pathway. 01:15:50 Only glucose can support the pentose phosphate pathway, which provides NAPDH and 5-carbon sugars for DNA; RNA, all of the energy carriers in energy metabolism (NADPH, NADH, FADH2, Coenzyme A, ATP); synthesis of nucleotides, neurotransmitters, fatty acids, and cholesterol; recycling of vitamin K and folate. 01:21:40 Insulin as a response to total energy and energetic versatility. Access the show notes, transcript, and comments here: https://chrismasterjohnphd.substack.com/p/045-is-insulin-really-a-response Chris Masterjohn, PhD, is the Founder and Scientific Director of the mitochondria test Mitome.