Glucagon and Diabetes: Everything You Need to Know

Glucagon and Diabetes: Everything You Need to Know

Glucagon is a hormone made by the alpha cells in our pancreas, and its job is to counteract insulin. It’s a really fascinating hormone, and people with diabetes aren’t often taught too much about it besides "it's always good to have a low blood sugar stash on-hand" or "carry your glucagon pen around for emergencies."

Glucagon promotes fat, protein, and glycogen breakdown, and inhibits fat, protein, and glycogen storage (insulin does the opposite). It also suppresses the release of insulin, and suppresses the action of insulin on insulin’s target tissues (muscle, liver, adipose tissue). All of these actions work to increase blood sugar.⁣

In a normally functioning system, insulin is released from beta cells and glucagon from alpha cells (both of which are in the pancreas) to inhibit each other when the level of one gets too high. This counteraction cycle functions to keep blood sugar levels stable.

When blood sugar levels drop to around 80-85 mg/dL in a person without diabetes, insulin secretion from beta cells in the pancreas stops. Once blood sugars drop to about 65-70 mg/dL, alpha cells in the pancreas start producing glucagon. The hormone tells the liver to release its stored glucose into the blood, which eventually raises blood sugar levels.

Do People With Diabetes Have Glucagon?

As people with diabetes, we are actually perfectly able to produce glucagon around blood sugars of 65-70 mg/dL. So why do we go low?

Because insulin inhibits the production of glucagon, as well as its actions on the liver (and vice-versa). In someone who is administering insulin differently (unnaturally) than the beta cells would, the normally functioning insulin-to-glucagon ratio becomes disproportionate. If we give ourselves too much insulin, our pancreas shuts down its glucagon response. ⁣

When we take too much insulin and go low, this excess insulin can inhibit glucagon production from our pancreas. Even if our body releases glucagon into the bloodstream, the glucagon can’t shut the insulin production off (because it’s already been given).

There are plenty of other things that can prevent your liver from releasing glucagon besides too much insulin. Your liver only stores about 100g of glucose. If you’re not eating enough, if you’re doing endurance sports without refueling, or if you’ve been drinking alcohol, your glucagon response will be impaired. Coupled with excess insulin, it can be bad news. ⁣

This is why when our blood sugar gets too low, as people with diabetes we can’t always rely on our own glucagon storage; instead, we have to exogenously administer it (through eating or by way of a glucagon pen), just like we exogenously administer insulin.

The Insulin Glucagon Balance

Replicating the natural stabilization of insulin and glucagon is the whole idea behind the emerging field of dual-chamber insulin pumps, closed loop systems, and artificial pancreases.

Current closed loop systems operate this in a very controlled manner (shutting off insulin brings glucose back up in part because glucagon is uninhibited). But it’s important to turn the insulin back on, because the total absence of insulin leading to uninhibited glucagon production is one of the reasons DKA happens -- the absence of insulin promotes ketone production, etc. by itself, but the absence of insulin also lets glucagon run amok and make everything worse. ⁣

And it doesn’t stop here! There’s so much more to this incredibly complex balancing system. In fact, there are a lot of other counterregulatory hormones that raise blood sugar in response to a low, like epinephrine! But that calls for an entirely independent post.

Ultimately, though, it’s an entire system of hormones that are working in tandem to keep that perfect blood sugar balance. Insulin and glucagon are just one part of this intricate balance-beam equation.

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Jordan Hoese, MD, MPH
Jun 15, 2020

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