Wednesday, December 21, 2011

The Glucagon Connection

Most of us understand the importance of insulin in controlling our blood glucose (BG) levels. When our BG levels get too high, we can bring them down by injecting insulin. Insulin is made in and secreted by the beta cells in the pancreas.

Many of us are also aware that another hormone, glucagon, helps bring BG levels up when they get too low. Glucagon is made in and secreted by the alpha cells in the pancreas.

In nondiabetics and people with type 2 diabetes or early type 1 diabetes, glucagon automatically gets secreted when BG levels get too low. But people with longstanding type 1 diabetes often stop producing much glucagon and need glucagon shots to bring up a serious low.

Insulin and glucagon are like the accelerator and brake on your car. And it's the ratio of the two, rather than the absolute amount, that is important. If you have almost no insulin, you might be able to have normal BG levels if you also had almost no glucagon.

In fact, a study done in 1981 in a man who had no pancreas, showed that BG levels could be maintained at about 100 without insulin as long as they didn't give the man glucagon.

The problem is that when the beta cells give out, the alpha cells don't give out as well. In fact, they often secrete even more glucagon than they would in a nondiabetic. Glucagon tells the liver to produce and secrete glucose, so the BG levels stay high even when you don't eat.

Most diabetes researchers focus on beta cells and insulin production, but some are studying the alpha cells and glucagon production as well. A recent study found that hyperglucagonemia (too much glucagon in the blood) actually precedes the decline in insulin secretion seen in diabetes.

These researchers infused rats with a lot of glucose for 10 days. After initial high BG levels, the rats adapted and maintained normal BG levels for 4 days. But then their BG levels started to go up, and by 10 days 89% of the rats had high BG levels.

This isn't surprising. The traditional view is that coping with a lot of glucose and producing a lot of insulin can "exhaust" the beta cells; this is called glucotoxicity.

But the researchers found that the rats weren't producing any more insulin than normal. Instead, their glucagon levels increased fivefold. Thus endogenous glucose production, production of glucose by the liver, was what was making the BG levels go up. And infusing them with anti-glucagon antibodies made their BG levels return to normal.

That is surprising.

The authors conclude that glucotoxicity may first manifest as alpha cell malfunction, before any deficit in beta cells and insulin secretion is seen. This is a new way of looking at how diabetes procedes.

A few months earlier, another paper showed that glutamate (or glutamic acid), an important neurotransmitter in brain and pancreas, is secreted from alpha cells along with glucagon. The glutamate contributes to beta cell destruction; it doesn't affect the alpha cells.

Hence, if you're secreting more glucagon, you'd also be secreting more glutamate, thus accelerating beta cell loss and insulin production when you needed more to oppose the extra glucagon.

The authors also found that the protein GLT1 (glial glutamate transporter 1) could protect the beta cells, and they are working on finding other beta-cell-protective compounds.

Neither of these discoveries will result in an instant cure for type 2 diabetes. The first was done in rodents, and the second was done in isolated human cells. Before they can be translated into actual diabetes treatments, they'd have to be replicated in humans, not isolated cells or rats, and treatments that turned down the alpha cells would have to be developed.

However, for decades, researchers have been studying how type 2 diabetes evolves, and they're still not sure. Of course it's all terribly complex. But is it possible people are looking in the wrong places? Maybe it's time for some new ways of looking at an old problem.

Focusing on the alpha cells is one such approach. Let's hope this work continues.

Tuesday, December 20, 2011

Closed Minds

I follow a low-carb (LC) diet to help control my type 2 diabetes. I can understand that this approach is very difficult for some people, and some with relatively mild type 2 can control despite eating more carbs.

But I'm always amazed at the closed-minded comments I often see in blogs of anti-low-carbers. Here's one, commenting on a photograph of a LC breakfast posted with a blog:

"There's nothing on the plate that I consider breakfast food."

The photograph seems to show bacon, ham, eggs, sausage, tomato, and mushroom.

I wonder why the poster feels that he needs special foods for breakfast. And apparently that special "breakfast food" should have a lot of carbohydrate, and little protein. That makes no sense. Most people are more insulin resistant at breakfast, and many studies have shown that blood glucose levels rise more after breakfast than after other meals. So if you feel a need for a daily allotment of orange juice, skim milk, toast, jam, and cereal, it would make more sense to eat it for supper, not breakfast.

Of course, this poster is not alone. Many people have irrational prejudices about "breakfast food." For instance, most Americans think bacon and ham are OK for breakfast. But if you say you had chicken or lamb chops, they'll think you're odd. Most Americans would consider Danish pastry or toast and jam to be suitable breakfast food. But if you say you had cheesecake or blueberry pie, they'll think you're odd.

What's the difference? Bacon, ham, chicken, and lamb are all meats. Danish, toast and jam, cheesecake, and blueberry pie are all sweetened starches.

It was the Kellogg brothers at the turn of the 20th century who pushed dry "breakfast cereals," at first primarily corn flakes, on the American public. At that time, rich people tended to eat meat and eggs for breakfast. Poor people ate starches, often boiled into porridge. Farm breakfasts tended to include a little of everything: meat, eggs, milk, pancakes, potatoes, breads, and pies. The farmers needed a lot of energy when facing long hours of backbreaking work and tended to eat the lighter meals like cereal in the evening.

By now, several generations of Americans have grown up thinking that breakfast has to include a dry cereal, often sweetened, and milk. But why do we have to mindlessly accept that there should be special "breakfast food"? We're smarter than that, aren't we?

In the rural area where I live, most people still conform to older patterns of eating. But in urban areas, it seems people are getting more creative with their meals, as described here. (The trend toward daylong snacking does not sound healthy, however, as commercial snacks are usually highly processed.) Nevertheless, the reporter reveals his underlying bias when he refers to eating nontraditional meals as "weird."

When we have diabetes, we need to eat the foods that keep our blood glucose levels down, whether they're considered "breakfast food" or "lunch food" or "dinner food." We can't let old patterns get in the way.

Lamb chops and broccoli for breakfast anyone?