Mitochondria and Insulin Resistance

I hadn't paid much attention to this whole mitochondria thing, mostly because it would require some sort of en masse genetic switcharooni for dysfunctional mitochondria to have spurned the epidemic in diobesetes* in this country (and around the world).  

I had just happened across the paper briefly discussed in my last post looking for something else.  It is interesting what a simple PubMed search on the apparent head of the research group:  Dr. John Holloszy turns up.  Lots and lots about mitochondrial biogenesis.  

One such paper is this fairly recent, 2008, review paper by Holloszy.  

I love finding these types of reviews.  They lead to a ton of research that has gone before, and do a lot of the "footwork" for anyone looking into these things.  Of course it's important to look at those, and not limit one's "looking into" to simply what the author cites.  Bias can rear its ugly head strongly in such papers.  The other thing about reviews is that they tend to read much more easily to the layperson.  It may be best to digest them in sections, but nonetheless they tend to be written more for a general audience of, at least, scientists in other fields than for specialized researchers with extensive backgrounds.

Such is how I find this paper.  I've not read a lot of Holloszy, but his work seems pretty solid at first glance.  I'll leave you with the abstract.  I'll also leave you with this.  If it is mitochondrial capacity that you're really after as the holy grail of metabolism and weight control -- EXERCISE is where it's at baaaaaybeeeeee!!!

Patients with type 2 diabetes, insulin-resistant obese individuals, and insulin-resistant offspring of patients with diabetes have ~30% less mitochondria in their skeletal muscles than age-matched healthy controls. It has been hypothesized that this ‘‘deficiency’’ of mitochondria mediates insulin resistance by impairing the ability of muscle to oxidize fatty acids (FAs). However, a 30% decrease in mitochondria should not impair the ability of muscle to oxidize FAs because the capacity of muscle to oxidize substrate is far in excess of what is needed to supply energy in the basal state, ie, in resting muscle. In pathologic states in which mitochondrial content/function is so severely impaired as to limit substrate oxidation in resting muscle, glucose uptake and insulin action are actually enhanced. Recent studies have shown that feeding rodents high-fat diets and raising FA concentrations results in muscle insulin resistance despite an increase muscle mitochondria that enhances the capacity for fat oxidation. Furthermore, it was recently shown that skeletal muscle mitochondrial capacity for oxidative phosphorylation in Asian Indians with type 2 diabetes is the same as in nondiabetic Indians and higher than in healthy European Americans. In light of this evidence, it seems highly unlikely that ‘‘mitochondrial deficiency’’ causes muscle insulin resistance.

*Diobesetes = the 80% of what is currently known as Type 2 diabetes.  Those for whom obesity led to the development of hyperglycemia. 


Dawn said…
Where does the asterisk after diabetes refer to?
Dawn said…
OK, don't bother answering -- I just noticed that it was "diobesetes" and found the footnote. (Duh!)

So what about people that are type 2 and normal weight?
CarbSane said…
Hi Dawn ... In your defense, I realized I forgot the footnote and edited it in (above deleted post didn't even get that part right LOL!) so perhaps not such a Duh moment on your part after all :)

I think the fatty acid hypothesis explains normal weight T2's well -- e.g. it's a dysfunction of fat tissue that causes too many lipids that should be stored there to be stored elsewhere that is the problem. Still, it simplifies discussions somewhat to limit them to the majority cases.
Rad Warrier said…
"If it is mitochondrial capacity that you're really after as the holy grail of metabolism and weight control -- EXERCISE is where it's at baaaaaybeeeeee!!!"

This and "calorie in calorie out" seem to apply beautifully to me. I did not really have excess weight to lose, but as part of diabetes control I began exercising and effortlessly lost about 8 kg (17.6 lb) in the process. Exercise greatly improved my blood sugar levels, lipid levels and also general health. Fortunately I did not have to resort to what I consider weird and miserable diets to keep diabetes in check.

CarbSane said…
Yep Rad! Congrats on your success with diabetes.
@ Rad I had the same experience and found through personal experimentation (or, lemme rephrase that as pretentiously as possible, n=1) that exercise makes a huge difference for me at the scale. That and CICO, as well, which I observe by following Weight Watchers religiously.

@ Evelyn Thanks for explaining this stuff about mitochondria - I noticed it seemed to be the topic du jour in the blogosphere & was wondering about it