Tag Archives: glucose

Could Glucagon Be Just as Important as Insulin in Diabetes?

I couldn't find a pertinent picture

I couldn’t find a pertinent picture

Everybody knows that insulin is the key hormone gone haywire in diabetes, right? Did you know it’s not the only one out of whack? Roger Unger and Alan Cherrington in The Journal of Clinical Investigation point out that another hormone—glucagon—is also very important in regulation of blood sugar in both types of diabetes.

Insulin has a variety of actions the ultimately keep blood sugar levels from rising dangerously high. Glucagon, on the other hand, keeps blood sugar from dropping too low. For instance, when you stop eating food, as in an overnight or longer fast, glucagon stimulates glucose (sugar) production by your liver so you don’t go into a hypoglycemic coma and die. It does the same when you exercise, as your muscles soak up glucose from your blood stream.

Glucagon works so well to raise blood sugar that we inject it into diabetics who are hypoglycemic but comatose or otherwise unable to swallow carbohydrates.

Glucagon also has effects on fatty acid metabolism, ketone production, and liver protein metabolism, but this post is already complicated enough.

So where does glucagon come from? The islets of Langherhans, for one. You already know the healthy pancreas has beta cells that produce insulin. The pancreas has other cells—alpha or α cells—that produce glucagon. Furthermore, the stomach and duodenum (the first part of the small intestine) also have glucagon-producing alpha cells. The insulin and glucagon work together to keep blood sugar in an fairly narrow range. Insulin lowers blood sugar, glucagon raises it. It’s sort of like aiming for a hot bath by running a mix of cold and very hot water.

Update: I just licensed this from Shutterstock.com

Update: I just licensed this from Shutterstock.com

Ungar and Cherrington say that one reason it’s so hard to tightly control blood sugars in type 1 diabetes is because we don’t address the high levels of glucagon. The bath water’s not right because we’re fiddling with just one of the faucets. Maybe we’ll call this the Goldilocks Theory of Diabetes.

When you eat carbohydrates, your blood sugar starts to rise. Beta cells in the healthy pancreas start secreting insulin to keep a lid on the blood sugar rise. This is not the time you want uncontrolled release of glucagon from the alpha cells, which would work to raise blood sugars further. Within the pancreas, beta and alpha cells are in close proximity. Insulin from the beta cells directly affects the nearby alpha cells to suppress glucagon release. This localized hormone effect is referred to as “paracrine guidance” in the quote below, and it takes very little insulin to suppress glucagon.

From the Ungar and Cherrington article:

Here, we review evidence that the insulinocentric view of metabolic homeostasis is incomplete and that glucagon is indeed a key regulator of normal fuel metabolism, albeit under insulin’s paracrine guidance and control. Most importantly, we emphasize that, whenever paracrine control by insulin is lacking, as in T1DM, the resulting unbridled hyperglucagonemia is the proximal cause of the deadly consequences of uncontrolled diabetes and the glycemic volatility of even “well-controlled” patients.

*  *  *

All in all, it would seem that conventional monotherapy with insulin is incomplete because it can provide paracrine suppression of glucagon secretion only by seriously overdosing the extrapancreatic tissues.

So What?

Elucidation of diabetes’ disease mechanisms (pathophysiology) can lead to new drugs or other therapies that improve the lives of diabetics. A potential drug candidate is leptin, known to suppress glucagon hyper secretion in rodents with type 1 diabetes.

RTWT.

Steve Parker, M.D.

PS: Amylin is yet another hormone involved in blood sugar regulation, but I’ll save that for another day. If you can’t wait, read about it here in my review of pramlintide, a drug for type 1 diabetes.

10 Comments

Filed under Causes of Diabetes

Are Fructose and High Fructose Corn Syrup Bad for Us?

Table sugar (sucrose) is a combination of glucose and fructose

Darya Pino earlier this month posted at her Summer Tomato blog a video regarding high fructose corn syrup.  The speaker in the video is pediatric endocrinologist Robert Lustig, M.D., of the University of California—San Francisco.
In the U.S. between 1970 and 1990, consumption of high fructose corn syrup increased over 1000%.  During those two decades, the incidence of overweight and obesity nearly doubled.  Many wonder if this is more than just coincidental. Most of this fructose is in soft drinks.  Soft drink consumption per person in 1942 was two servings per week.  In 2000, consumption was two servings per day.  Of course, these drinks typically have few nutrients other than sugars.

Dr. Lustig is convinced that high fructose corn syrup (HFCS) is a chronic toxin, at least in the amounts many of us eat, and the cause of our current epidemic of childhood and adult obesity and overweight.  Even if this idea is not new to you, you may be interested to hear the biochemistry and physiology behind his position.  If you didn’t enjoy college lectures or are not a food science geek, you probably won’t be able to sit through this 1.5-hour video. 

I enjoyed the heck out of it!  Made me feel like I was back in college again.  Few of my professors were as good as Dr. Lustig at lecturing. 

Here are a few of his other major points:

  • HFCS was invented in Japan in the 1960s, then introduced to U.S. markets in 1975
  • sucrose and fructose are both poisons
  • in the U.S. we eat 63 pounds (28.6 kg) of HFCS and 141 pounds (64.1 kg) of sugar per year [he didn’t define “sugar” in this context]
  • he praises Yudkins book, Pure, White, and Deadly [I’ve written about the Cleave-Yudkin carbohydrate theory of chronic disease]
  • the triglyceride/HDL ratio predicts heart disease much better than does LDL cholesterol
  • chronic high fructose intake causes the metabolic syndrome [does he think it’s the only cause?]
  • only the liver can metabolize fructose, in contrast to every other tissue and organ that can use glucose as an energy supply
  • high fructose consumption increases the risk of gout and high blood pressure
  • fructose interferes with production of our body’s production of nitrous oxide—a natural circulatory dilator—leading to higher blood pressures
  • fructose increases de novo lipogenesis—in other words, it creates body fat
  • fructose interferes with natural chemical messengers that tell your brain you’ve had enough food and it’s time to stop eating
  • high fructose intake reduces LDL particle size, potentially increasing the future risk of cardiovascular disease such as heart attacks [small, dense LDL cholesterol is more damaging to your arteries that large, fluffy LDL]

So What? 

You don’t need polititians to reduce your consumption of sugary soft drinks and high fructose corn syrup—do it yourself starting today.  Read food labels—HFCS is everywhere.  I’ve found it in sausage! 

The food industry greatly reduced use of trans fats in response to consumer concerns, before the polititians ever dabbled in it.  HFCS can go the same route.  Consumption of soft drinks, sports drinks, and other sugary beverages—the major sources of HFCS—is up to you.

Steve Parker, M.D.

PS: The Advanced Mediterranean Diet and Ketogenic Mediterranean Diet are naturally low in fructose.

2 Comments

Filed under Carbohydrate, Causes of Diabetes, Overweight and Obesity, Shameless Self-Promotion