Most of us have learned a lot about insulin, the hormone produced by the beta cells that works to let muscle and fat cells take up glucose from the blood, hence keeping our blood glucose (BG) levels at healthy levels.
We know that if we have diabetes we don’t have enough insulin to keep those BG levels in healthy ranges. Even if we have type 2 diabetes, and we’re still producing a lot of insulin, our insulin resistance is making that insulin a lot less effective, so we have relative insulin deficiency.
If we can reduce our insulin resistance enough, then the insulin we’re able to produce might be sufficient.
But there’s another player in this equation: glucagon. And it’s the ratio of the two that determines your BG levels.
Most of us are aware that glucagon can increase BG levels when we go too low. People who are injecting insulin and who sometimes have very low BG levels can keep a glucagon kit on hand so they – or often someone else – can give a shot of glucagon to quickly bring those levels up.
This is especially important in people who have had type 1 diabetes for a long time, because their own glucagon production tends to decline with time, making the low BG episodes potentially more serious.
But glucagon plays a large role in type 2 diabetes as well. When we have type 2 diabetes, not only is our insulin not sufficient to keep BG levels in check, but our glucagon levels are too high. It’s as if our brakes (insulin production) are shot and our accelerator (glucagon) is stuck on high.
Normally, after a meal, the higher BG levels tell the alpha cells in the pancreas to shut off their production of glucagon, and less glucagon tells the liver to stop releasing glucose into the bloodstream. It’s not needed. The food can now do the job.
But when we have type 2 diabetes, that message often doesn’t get through. So after a meal we’re not only absorbing glucose from the food we just ate, but our liver is still shipping glucose out into the bloodstream to make the BG levels go even higher: a sort of double whammy.
Most of the drugs we have today deal with the insulin side of the equation. You can simply inject more insulin or take oral drugs that reduce your insulin resistance or take other drugs that increase the amount of insulin your own body produces or that slow down the digestion of carbohydrate in the intestine.
Metformin does act at the level of the liver to keep the liver from producing more glucose from other types of food, but it does this by inhibiting gluconeogenesis – the process that makes glucose out of protein (actually, amino acids, the building blocks of protein) and the fat backbone called glycerol as well as a few other products of metabolism – rather than affecting glucagon levels.
One exception is Byetta and other GLP-1 mimics. They not only stimulate insulin secretion from the beta cells but also decrease glucagon production. In some people, these drugs are very effective.
When we know more about how glucagon levels are controlled, we will undoubtedly advance our understanding of type 2 diabetes. For more on this topic, see here.