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.
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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.
