Chris Masterjohn, PhD shares his thoughts if Insulin Really a Response to Blood Glucose?
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Chris Masterjohn, PhD shares his thoughts if Insulin Really a Response to Blood Glucose?

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.

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Show Notes for “Is Insulin Really a Response to Blood Glucose?”

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 NADPH 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.

Masterclass Lessons Related to “Is Insulin Really a Response to Blood Glucose?”

Lactate: Rescuing NAD+ and Generating ATP From Glycolysis | MWM 2.15

Anaplerosis: Why Carbs Spare Protein in Ways That Fat Can’t | MWM 2.16

Is Insulin Really a Response to Carbohydrate or Just a Gauge of Energy Status? | MWM 2.23

The Pentose Phosphate Pathway: How Glucose Supports Antioxidant Defense, Detoxification, Nutrient Recycling, and Far More | MWM 2.27 (coming soon to MWM Pro subscribers, scheduled for public release on August 9).

Insulin as a Gauge of Short-Term Energy Supply and Energetic Versatility | MWM 2.28 (coming soon to MWM Pro subscribers, scheduled for public release on August 11).

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Other Posts Podcast Episodes Related to “Is Insulin Really a Response to Blood Glucose?”

The Biochemistry of Why Insulin Doesn't Make You Fat | Mastering Nutrition Episode 44

Paleo f(x) Grab Bag: Carbs, Sex Hormones, Type 1 Diabetes, and More | Mastering Nutrition Episode 11

Why “Glycation” Is a Bad Reason to Restrict Carbs | Mastering Nutrition Episode 6

What Is Measuring Our Hba1c REALLY Telling Us About Our Blood Glucose and Diabetes Risk? | Mastering Nutrition Episode 12

Wait a Second, Is Glycation Actually GOOD For You? | Mastering Nutrition Episode 13

Examine.Com Editorial: Sugar is the Ultimate Antioxidant and Insulin Will Make You Younger

Research and Educational Resources Related to “Is Insulin Really a Response to Blood Glucose?”

Kawai et al. Postprandial glucose, insulin and glucagon responses to meals with different nutrient compositions in non-insulin-dependent diabetes mellitus.1987

Komatsu. Glucose‐stimulated insulin secretion: A newer perspective. 2013.

Keane and Newsholme. Metabolic Regulation of Insulin Secretion. 2014

Tortora, Principles of Anatomy and Physiology: 14th Edition , 2013, pp. 906-9, 642-6. 752-4, 787-8, 801-2, 912, and 920-2.

Byers et al. Avian and Mammalian Facilitative Glucose Transporters. 2017.

Kersten. Physiological regulation of lipoprotein lipase. 2014.

Cruz et al. Glucose and Insulin Stimulate Heparin-releasable Lipoprotein Lipase Activity in Mouse Islets and INS-1 Cells A POTENTIAL LINK BETWEEN INSULIN RESISTANCE AND β-CELL DYSFUNCTION. 2001.

Nyrén et al. Localization of lipoprotein lipase and GPIHBP1 in mouse pancreas: effects of diet and leptin deficiency. 2012.

Kalwat and Cobb. Mechanisms of the amplifying pathway of insulin secretion in the β cell. 2017.

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  1. Hi Chris! I have just discovered your site thanks to a recent Peter Attia podcast. Very interesting!

    I have 1 comment to this 2y old podcast (will you even see it?) and that is another perspective on the role of insulin and why glucose is such a trigger for it. It comes from the point of view of long-term fasting (which, I know, you’re not a fan of). From this POV the primary role of insulin is to switch off liver’s gluconeogenesis and ketogenesis The insulin level itself is very low during a fast, so it plays hardly a role in all the other pathways you described in such a great detail here. And yet it is of paramount importance, since without this off switch, the precious endogenous fuel sources, especially protein, will not be quite so economically utilized. Or worse yet, the body will go into the death spiral of diabetic ketoacidocis (which happens entirely because in 1st type diabetes there is no insulin to stop the body meltdown).

    Also, knowing of fuels sources and ways of their utilization during a fast, it becomes plainly clear why insulin reacts so much stronger to glucose than other fuels: glucose is very expensive on a fast! So as soon as a sufficient level is reached, its production by the liver must be immediately stopped (until a low level causes glucagon to turn it on again).

    See how from the POV of fasting, the main role of insulin is to stop gluconeogenesis. Everything else is secondary. Of course, the same metabolic mechanisms operate also when we eat, though presence of various exogenous nutrients greatly complicates the picture. But if you dismiss all these exogenous factors then a very clear picture emerges. The study of metabolism of long-term fasting allows just that.

    sorry for my inadequate English and btw I also very much admire your eloquence 🙂

  2. Why is this site keep saying (my email is not valid???)
    I’ve had/used this email for 10 years!
    Please respond and explain !
    thank you.

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