Tuesday, January 17, 2012

Biotin Ameliorates Skeletal Muscle Insulin Resistance in Model of Type II Diabetes. Increase in GLUT-4 Expression Yet not Accompanied by Translocation to Cell-Membrane

Image 1: Otsuka Long-Evans Tokushima fatty rats (OLETF, right) have the genetical disposition to become type II diabetics.
Are your nails brittle? Is your hair falling out? No? Then, are you obese or insulin resistant? Yes? ... I guess, by know you are asking yourselves what your hair and nails have to do with your pre-diabetic beer-belly. Well, according to the recently published restults from a study by Yuka Saki and his Japanese colleagues, biotin, the water-soluble nutrient that has been discovered by Bateman in 1916 and is also known as vitamin B7, vitamin H or coenzyme R could well be the missing link. After all, the well-known, but often misunderstood micronutrient plays a central role in both fatty acid, as well as glucose metabolism and is by no means just a "hair & nails" vitamin.

Biotin could help even if "it's in your genes" ;-)

The Japanese researchers used the infamous Otsuka Long-Evans Tokushima fatty rats whose name already implies that their have the unfortunate propensity to gain tons of body fat and develop type II diabetes, even if they are not fed the "high fat" diet (of which at least those of you who are not the first time here at the SuppVersity should know by now that it is high in fat and carbs) to check, whether supplementation could ameliorate the inevitable development of skeletal muscle insulin resistance in these poor critters.
Figure 1: Body weight, fasting glucose and insulin levels at the beginning and end of the 8-week study period (data adapted from Sasaki. 2012)
If you look at the results of the 8 week treatment period in the course of which the 34-week old, already overweight (compared to the non-diabetic LETO group) OLETF rats received either plain water or water with 3.3mg/L biotin (i.e. ~400µg/kg biotin for a rat and 65µg/kg for a human being), the treatment did in fact have the desired effect on glucose and insulin levels (cf. figure 1). The increase in insulin sensitivity, on the other hand, "allowed" the biotin-treated OLETF rats to gain even more weight than their profoundly diabetic peers. This, by the way, is something you will also see in humans, who - just as their omniscient Dr. told them - take their diabetic drugs and / or insulin, but refuse to make the necessary dietary and lifestyle changes.
Figure 2: Glucose uptake, total and membrane GLUT-4 expression in hindlimb muscle of 42-week old OLETF rats with or without biotin treatment (data calculated based on Sasaki. 2012 and expressed relative to non-diabetic LETO control)
What is also interesting is that despite a significant increase in total GLUT-4 (glucose transporter) expression in the skeletal muscle of the OLETF rats, a concomitant increase in receptor translocation to the cell-membrane, of which you have probably read in previous blogposts that it is responsible for the exercise-induced increase in glucose uptake, did not take place (cf. figure 2). Consequently, the glucose uptake in the hindlimb muscle did increase in response to biotin supplementation, but failed to reach the same (100% in figure 2) level as in the non-diabetic control group.

Biotin does not via AMPK... good or bad news?

These observations lead the scientists to conclude that the mechanism that is responsible for the nevertheless beneficial effects of supplemental biotin can not be a direct consequence of AMPK activation, which is at the heart of both exercise, as well as drug (esp. Metformin) induced ameliorations in insulin sensitivity. This is something, I actually find pretty interesting, because a) the elucidation of the exact mechanism by which biotin is able to increase insulin sensitivity and skeletal muscle glucose uptake could lead to novel insights into skeletal muscle glucose metabolism which could also be of relevance for "physical culturists", and b) if biotin, despite being essential for the activation of Acetyl-CoA carboxylase (ACC), a major downstream target of AMPK, does not work by "simply" stimulating the AMPK pathway, it is actually likely that the effects of biotin supplementation and exercise could add up.