Wednesday, July 20, 2005

This is interesting: a piece on the discovery of the protein released by fat cells that is the mechanism for insulin resistance.

I have my doubts that this will lead to desirable treatments, though, because it seems likely the insulin resistance mechanism exists for the purpose of keeping people from getting fatter. Disabling it will probably cause them to exchange diabetes for greater obesity.

UPDATE: The always-cogent INDC Bill says "I don't understand why you come to that conclusion," and points to a study showing that insulin-insensitivity reduces glucose-induced thermogenesis.

My understanding is that the diabetic's fat causes him to suppress insulin usage (by producing the protein mentioned above). Now we even have the mechanism for that process identified.

Why would suppressing insulin resistance make people fatter? Harkening back to my bodybuilding days, I believe it was explained to me that insulin makes fat out of glucose by telling your cells to bind together three glycogen molecules into a triglyceride (fat). This is one way insulin reduces blood sugar, which is its main function as far as your body is concerned, because glucose makes your blood more acidic and thus more toxic, which is why people who can't make/use enough insulin to lower their blood sugar go blind and get cardiovascular disease at much higher rates.

Bill's link seems to raise a insulin-insensitivity counter-effect: reduced glucose-induced thermogenesis, which I'm assuming is due to the receptor-based shutoff of insulin transport function that brings glucose into your cells to be used for fuel. I would further assume, however, that this is not enough to offset the direct fat production and ketosis-suppressing effect of insulin's influence in the cell (which a drug that reduces insulin insensitivity would be intended to increase).

(Insulin insensitivity is, I think, best-understood from the perspective of receptor fatigue. This is something anyone who has used a testosterone-based supplement is familiar with: no matter how much testosterone you take, within a few weeks your muscle cells stop responding to the excess testosterone and you stop gaining muscle mass. This is because your cells make fewer and fewer receptors; it's a self-limiting system.)

"In healthy humans, age, lean mass and respiratory quotient are the main independent determinants of resting thermogenesis. In contrast, insulin sensitivity and, to a lesser extent, abdominal obesity are the principal factors controlling glucose-induced thermogenesis."

Interesting that it's only glucose-induced thermogenesis that's affected; that means carb-induced. It does seem plausible that if the person continues to consume carbohydrates the secondary effect could be enough to make them continue to gain weight. I wonder if it's simply assumed the cycle is self-reinforcing because their (misinformed) dieticians tell them to reduce fat intake but keep eating carbs.

IMHO, diabetes is basically carbohydrate poisoning.

FWIW, I think we'll find out for sure which effect is stronger. Someone will probably develop and start testing a drug to suppress this protein. I don't think they'll be especially pleased with the results, though trading fat for blindness is probably a plus.

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