Confirmed: All Wheys, Not Just Hydro Whey Boost Glucose Uptake And Liver + Muscle Glycogen Supercompensation. Plus: How Could Taurine Be Involved in This Benefits?

Do it or don't? If the question is about consuming whey protein, the answer is clear: Do it! Use whey!
As a diligent student of the SuppVersity you will remember my previous article "The Glucose Repartioning Effects of Isoleucine: Falsely Underappreciated BCAA and Its Dipeptides Maximize GLUT-4 Expression and Ramp Up Muscular Glucose Uptake" (read more). If you don't let me briefly bring you up to speed in back in February, I told you about the beneficial effects of a class of isoleucine peptides in whey protein hydrosylate [as the study at hand goes to show you, this is important, see bottom line] on glucose transporter (GLUT-4) expression and thus glucose uptake in skeletal muscle.

Today I am pleased to be able to continue and expand on this discussion based on the results of the latest study from the same group of researchers from Sao Paulo, Brazil (Morato. 2013).

Whey, an anti-diabetic glycogen supercompensation tool

As Morato et al. point out, their own study is by no means the only one that supports the very special insulin sensitizing activity of whey proteins. In fact, whey is already touted as potential anti-diabetic. If the medical orthodoxy or rather it's "legislative" arm was not trapped by its own dogmas WPH [whey protein hydrolysate] would already be a central part of the dietary recommendation for type II diabetics. With the current study being the first to show that a whey protein based diet will lead to chronically increased GLUT-4 expression and thus help to lower blood glucose and improve glycogen storage, the study at hand is albeit similarly interesting for the average musclehead and his obese type II diabetic neighbor.
Figure 1: Effects of casein, whey and whey hydro(lysate) diets on GLUT-4 expression, baseline insulin, liver glycogen and muscle glycogen levels (g/100g tissue; Moreto. 2013)
Apropos obese neighbor. You should go and convince him to go to the gym with you. After all, the rodent data in figure 1 clearly shows that WPH leads its trumps only when it is combined with training - in this case treadmill running for 60 minutes at 15 m/min (the exercise took place 16 h before the sacrifice; so the increases are not in response to the exercise! they are just amplified by chronic endurance during).

Suggested read: "The Overlooked Glucose Repartioning Effects of Isoleucine" (read more)
While exercise alone is well known to boost GLUT-4 expression and subsequent glucose uptake significantly (Christ-Roberts. 2004; Kuo. 2004; note. GLUT-4 activity correlates with the degree of muscular clycogen depletion, so no "5 min rest, 2 sets all out and go home workouts!"), the addition of a whey protein hydrosylate with a pre-hydrolysation level of 12.5% (think of it as being enzymatically "pre-digested) as the sole protein component of the baseline diet (15% protein total, 7% fat from vegetable oil, 68% carbs from sugar and corn starches) of the 48 male Wistar rats in the experiment at hand did turn the +100% increase from exercise alone into a  +160% increase.

I have to admit, the increased GLUT-4 uptake per se may not be news, but this is in fact the first chronic feeding study where it was observed in conjunction with higher glycogen levels - ca. 90%, 70% and a whopping 400% in the heart, the musclulature and the liver in the sedentary state for both WPH and regular whey protein. That's certainly impressive, but you got to remember that this is a result of combining whey with a high carbohydrate diet (69% of the diet vs. 7% fat) which provides the necessary readily available substrate for optimal glycogen super-saturation (=packing in more glycogen than you usually could).

You will and can very well live with the insulin spike!

Though it may not look like it in figure 1, you got to be aware that the values were not taken right after the ingestion of a meal, let alone a protein shake. In other words, it is almost certain that the whey protein groups will have had higher insulin levels immediately after a meal (note: Casein is still way more insulinogenic than meat or eggs).
I've gone into quite some detail on why insulin spikes (in the presence of glucose) are not a problem, but rather a vital necessity in a previous post (read it)
"One of the primary means to increase the concentration of GLUT-4 in the plasma membrane is through insulin-regulated trafficking (Zorzano. 2005). However, in the present experiment, no increase was noted in serum insulin levels in the groups consuming WPH.

The experimental design of the study focused on the moment of greatest mobilization of glucose transporter-4, and the animals were sacrificed 2 h after consuming the meal; this was too long an interval to observe the maximum plasma insulin response." (Morato. 2013)
It is thus a given that the  GLUT-4 translocation was at least supported by profound and temporary (at least in the presence of an adequate carbohydrate intake, their temporary nature is what makes the whey induced insulin spikes physiologic and beneficial vs. pathological and detrimental as chronic elevations would be; learn more). According to Morato et al. this is however not the only way the ingestion of whey affected the translocation of GLUT-4 (upstream) and the subsequent uptake of glucose into the muscle and liver (downstream):
Translocation of GLUT-4 to the PM [plasma membrane] can also be stimulated in an insulinindependent manner. Carneiro et al. (2009) accomplished this through taurine activation of the insulin pathway, thus raising the GLUT-4 concentration in the plasma membrane independent of insulin. However, the molecular mechanism behind this effect has still not been elucidated (Carneiro. 2009).

There is actually evidence that would suggest that whey protein hydrolysate is not simply not superior, but actually inferior to regular whey proteins when it comes to improvements in body composition in athletes (read more)
In the exercised animals of the WP and WPH groups, the plasma concentrations of taurine (Table 1) were greater (p,0.05) than those in the control group consuming CAS. This could explain, at least in part, the greater translocation of GLUT-4 in the WP and WPH groups.

After investigating the amino acid composition of the WP and WPH, it was found they were rich in sulfur amino acids (Table 2), and methionine and cysteine are endogenous precursors of taurine. Thus, the consumption of WP or WPH provided a greater amount of substrate for the endogenous production of taurine than casein, and the presence of this amino acid may have facilitated activation of the insulin pathway and cell capture of glucose, as indicated in the literature." (Morato. 2013; my emphases)
That's quite a surprising insight, isn't it? I mean, as a SuppVersity reader you have long known about the anti-diabetic prowess of taurine, but who would have suspected that it could be #3 alongside the active isoleucine dipeptides and the insulin release among the mechanisms behind the profound beneficial effects whey has on glucose? I mean, there is basically no taurine in whey.
SuppVersity readers have known for years, that whey is far superior to an amino acid (AA) mixture with the same AA make-up (read more)
Bottom line: Yep, this is support for a previous advice I've gicen: You better never run out of whey protein for both, health and performance reasons. Personally, I am yet most fascinated by the potential involvement of endogenous (=your body's own) taurine synthesis. That 's certainly going to be a topic in Sunday's 2nd installment on supplements to improve and maintain insulin sensitivity (read part I on lifestlye modifications here).

Pratically speaking the most important and eventually less surprising message of the study at hand is however that it does not necessarily have to be whey protein hydrolysate. The regular whey protein did an outstanding job, as well, and the "real-world" = visible / noticeable differences are propably non-significant.

In this context, some of you may also remember the results from another recently published study by Lollo et al. (read it) which did in fact suggest that the muscle building and body recompositioning effects of whey hydrolysate are inferior and not superior to those of regular whey.

  • Carneiro EM, Latorraca MQ, Araujo E, Beltra M, Oliveras MJ, et al. Taurine supplementation modulates glucose homeostasis and islet function. J Nutr Biochem. 2009; 20: 503–511.
  • Christ-Roberts CY, Mandarino LJ. Glycogen synthase: key effect of exercise on insulin action. Exerc Sport Sci Rev. 2004; 32: 90–94.
  • Kuo CH, Hwang H, Lee MC, Castle AL, Ivy JL. Role of insulin on exercise-induced GLUT-4 protein expression and glycogen supercompensation in rat skeletal muscle. J Appl Physiol.  2004; 96: 621–627.
  • Morato PN, Lollo PC, Moura CS, Batista TM, Carneiro EM, Amaya-Farfan J. A dipeptide and an amino acid present in whey protein hydrolysate increase translocation of GLUT-4 to the plasma membrane in Wistar rats. Food Chem. 2013 Aug 15;139(1-4):853-9.
  • Zorzano A, Palacín M,Gumá A. Mechanisms regulating GLUT 4 glucose transporter expression and glucose transport in skeletal muscle. Acta Physiol Scand. 2006. 183: 43–58.
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