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23. Is Insulin Really a Response to Carbohydrate or Just a Gauge of Energy Status?

Lesson 23 of Masterclass With Masterjohn: The Antioxidant System

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Insulin secretion.

Remarkably, we know from dietary studies that we get the most insulin from eating carbohydrate, yet we know from molecular and cellular studies that insulin secretion is primarily triggered by the ratio of ATP to ADP inside the pancreatic beta-cell. The former implies that insulin is a response to glucose, while the latter implies that insulin is a response to total energy availability.

What can explain this discrepancy?

In this lesson, we explore the possibility that it is the anatomy and physiology that drive the dietary effect of carbohydrate rather than the biochemistry. Carbs are wired to get soaked up by the pancreas when blood sugar rises above the normal fasting level once the liver has taken its share to replete hepatic glycogen, whereas fats are wired to go primarily to the heart and muscle when those organs need energy and to go primarily to adipose tissue otherwise. The combination of circulatory routes and the relative expression of glucose transporters and lipoprotein lipase by different tissues likely directs fat to the pancreatic beta-cell as a source of ATP only during extreme hyperglycemia or when it exceeds adipose storage capacity due to obesity, insulin resistance, or very high-fat meals.

The pancreatic beta-cell does have a diversity of complicated and often controversial secondary biochemical mechanisms that “amplify” the insulin-triggering effect of ATP, and carbs are more versatile at supporting these mechanism than fat. These likely make a contribution to the dietary effect, but they strike me as unlikely to be the primary driver of the dietary effect.

Thus, insulin is a response mainly to carbohydrate availability but also to total energy availability, and this driven mainly by the anatomy and physiology but also by the biochemistry.

Seeing insulin as a response to cellular energy status will eventually help us broaden our view of insulin as a key governor of what to do with that energy that goes far, far beyond regulating blood glucose levels.

The audio and video of the first three lessons of this course are available to everyone for preview, but lessons 4-39 are for Masterpass members only. Start a preview from the beginning here. To learn more about the Masterpass, click here.

The full video is for paid subscribers

Harnessing the Power of Nutrients
Masterclass With Masterjohn: Energy Metabolism
This is a course with 39 lessons on the biochemistry of how we burn carbohydrate and fat for fuel.
Chris Masterjohn, PhD