Glucagon, Dietary Protein, and Low-Carbohydrate Diets

Glucagon is a hormone that plays an important role in blood glucose control.  Like insulin, it's secreted by the pancreas, though it's secreted by a different cell population than insulin (alpha vs. beta cells).  In some ways, glucagon opposes insulin.  However, the role of glucagon in metabolism is frequently misunderstood in diet-health circles.

The liver normally stores glucose in the form of glycogen and releases it into the bloodstream as needed.  It can also manufacture glucose from glycerol, lactate, and certain amino acids.  Glucagon's main job is to keep blood glucose from dipping too low by making sure the liver releases enough glucose.  There are a few situations where this is particularly important:

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Is Sugar Fattening?

Buckle your seat belts, ladies and gentlemen-- we're going on a long ride through the scientific literature on sugar and body fatness.  Some of the evidence will be surprising and challenging for many of you, as it was for me, but ultimately it paints a coherent and actionable picture.

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The Brain Controls Insulin Action

Insulin regulates blood glucose primarily by two mechanisms:

1. Suppressing glucose production by the liver
2. Enhancing glucose uptake by other tissues, particularly muscle and liver

Since the cells contained in liver, muscle and other tissues respond directly to insulin stimulation, most people don't think about the role of the brain in this process.  An interesting paper just published in Diabetes reminds us of the central role of the brain in glucose metabolism as well as body fat regulation (1).  Investigators showed that by inhibiting insulin signaling in the brains of mice, they could diminish insulin's ability to suppress liver glucose production by 20%, and its ability to promote glucose uptake by muscle tissue by 59%.  In other words, the majority of insulin's ability to cause muscle to take up glucose is mediated by its effect on the brain. 

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Choline and Fatty Liver

I've been writing about non-alcoholic fatty liver disorder (NAFLD) since the early days of this blog, because it's an alarmingly common disorder (roughly a quarter of Americans affected) that is typically undiagnosed. It often progresses into its more serious cousin non-alcoholic steatohepatitis (NASH), an inflammatory condition that causes liver damage and can progress to cancer. In a number of previous posts, I pinpointed excess sugar and seed oil consumption as culprits in NAFLD and NASH (1, 2, 3, 4, 5).

Chris Masterjohn recently published two very informative posts on NAFLD/NASH that add a major additional factor to the equation: choline (6, 7). Choline is an essential nutrient that's required for the transport of fat out of the liver (8). NAFLD can be caused, and cured, simply by removing or adding dietary choline, and it appears to be dominant over other dietary factors including fat, sugar and alcohol. Apparently, certain researchers have been aware of this for some time, but it hasn't entered into the mainstream consciousness.

Could that be because the richest dietary sources are liver and eggs*? Choline is also found in smaller amounts in a variety of whole animal and plant foods. Most people don't get the officially recommended amount. From a recent review article (9):

Mean choline intakes for older children, men, women, and pregnant women are far below the adequate intake level established by the [Institute of Medicine]. Given the importance of choline in a wide range of critical functions in the human body, coupled with less-than-optimal intakes among the population, dietary guidance should be developed to encourage the intake of choline-rich foods.

I've dubbed beef liver the Most Nutritious Food in the World, Nature's Multivitamin, and I'll probably invent other titles for it in the future. Add yours to the comments.

Head over to Chris's blog and read about the classic studies he unearthed. And add The Daily Lipid to your RSS reader, because there's more interesting material to come!

The Sweet Truth about Liver and Egg Yolks
Does Choline Deficiency Contribute to Fatty Liver in Humans?


* For the brave: brain is actually the richest source of choline.