Saturday, May 12, 2012

Chronic Albuterol Treatment Improves Glucose Uptake in Skeletal Muscle: Could Your Beloved Coffee Do the Same?

Image 1: If there is a connection between asthma and diabetes, it probably isn't related to the use of beta-2 agonists.
What is one of the most dubious ailments among professional athletes? Asthma, right! Asthma is much better than the meat in Lenny Paul's bolognese of which he claimed that it must be responsible for the nandrolone the WADA officials found in his bloodstream 1997. I mean, even if you don't want to say that you used it yourself the truckload of clenbuterol (once used as a standard treatment for asthma) could still be for your poor asthmatic dog like the one professional cylcist, Frank Vandenbroucke, had squirreled away in his house just when the WADA ransacked his house. Now, less than a month after the publication of a study by Hamzeh Elayan, Milos Milic. Ping Sun, Sunir Gharaibeh and Michael G. Ziegler in the Journal of Cellular and Molecular Neurobiology (Elayan. 2012), I suppose that the next top athlete who is going to be busted will probably claim that the salbutamol (a shorter acting "brother" of clenbuterol that is also know as "albuterol" in the US) in his kitchen sink is for his diabetic cat, rodent or even parrot.

Long-term vs. short-term effects of beta-2-antagonists

The main message of the results the scientists present in their paper is that the short- and long-term (side-)effects of certain drugs (including those we always believed we know quite well) can be very different, if not diametrically opposed. While acute treatments with epinephrine and b2-agonist drugs have been shown to decrease insulin resistance, Elayan et al. were able to show that only the addition of 50 mg/1,000 ml of the selective b2-adrenoceptor agonist, salbutamol to the drinking water of the exercised mice, was able to improve both the response to a glucose challenge, as well as the insulin response in a rodent model of type II diabetes.
Figure 1: Glucose levels in salbutamol group during insulin tolerance test at 20, 40, 60, 100 and 120 min in week 4 and week 8 (4w-ex / blue and 8w-ex / red) and 5 weeks after cessation of exercise (green); data expressed relative to exercised control group (calculated based on Elayan. 2012)
And though it may be that this effect was particularly pronounced in the older mice in the study at hand, previous studies by Ziegler et al. yielded similar results (protection against overfeeding induced obesity) in younger rodents upon direct administration of exogenous epinephrine.
Note: If you take a closer look at what you see in figure 1 you will notice that the effects of albuterol / salbutamol are not reliant on concomitant exhaustive treadmill exercise; after all, the improved insulin tolerance of the albuterol group persisted 5 weeks after cessation of the exhaustive exercise regimen.
Since the epinephrine output decreases with age, it is still reasonable to assume that lower exercise induced surges in epinephrine in the 8-month old C57BL6 mice of the study at hand may have contributed to the lack of improvement in the insulin tolerance test in exercise only group of the study at hand.

From clenbuterol & co to your morning coffee

Although I would hope that no one here suffers from either "athlete's" let alone real asthma, these results may well have real-world significance for you, as well. After all, the same "bad" hyperglycemic effects that have been ascribed to albuterol, clenbuterol & co, constitute one of the major arguments against the use of caffeine and related stimulants. The first link that pops up, when you type "diabetes coffeine epinephrine" into google, for example tells you how hazardous the adrenaline (=epinephrine) is for insulin resistant patients. And while the author of this article has several studies ready to validate the point she is making, those studies studies looked at the short-term effects of coffee consumption only.

Image 2: Gross, but true! In view of the fact that no more than 250kg of the "cat's poop coffee", Kopi Luwak, are produced every year, 80$ per cup does not seem too expensive. I mean, compare that to your average Starbucks or McCaffee brew! With Kopi Luwak you do at least know whose poop it was that is responsible for its distinctive taste ;-)
As far as the long-term effects are concerned you could however speculate that the decreased incidence of diabetes in habitual coffee drinkers (van Dam. 2005) could - at least in parts - be mediated through the same pathways as those Elayan et al. observed in their rodent study; pathways, of which they speculate that it is mediated by epinephrine induced phosphorylation of AMPK (read all about AMPK here) and subsequently increased expression of the glucose transporters GLUT-4 in skeletal muscle and the ability of beta-2-adrenergic drugs to induce a profound PGC-1alpha response, which has only recently been hailed as yet another target for "exercise in the pill" (cf. "Irisin: Exercise in a pill?"). That the latter, i.e. PGC-1alpha also leads to improved mitochondrial respiration and could thusly help with all sorts of neurological pathologies could also explain why studies such as Maia et al. found an independent negative association (=the more the less) between caffeine intake and the incidence of Alzheimer's disease (Maia. 2002).

From oral stimulants to insulin injections? Probably only if you go totally overboard

Assuming that you don't overdo it on coffee, caffeine (my experience is that from 600mg+ per day and individual doses >300mg the negative side effects prevail), it is thus unlikely that the combined epinephrine release from your morning coffee and your pre-workout supplement will predispose you to develop diabetes. That they are not going to counter the negative effects of bad dietary habits should however be as obvious, as the fact that this does not diminish the potential health hazards of acute doses in the 600-800mg range could pose to non-alcoholic fatty liver disease (NAFLD) patients (cf. "355% Increase in VLDL Due to High Dose Caffeine in Rodent Model of NAFLD")