Hydrolysate milk protein serum can help to combat hyperglycemia

A study conducted at a Brazilian university shows that the effects of whey go far beyond increased muscle mass and could be an important tool for controlling diabetes.

By José Tadeu Arantes

Agência FAPESP – Milk protein serums are a very familiar nutritional supplement for athletes. Generically known as whey proteins, they are sold under several brand names and in a variety of presentations.

Thanks to their wealth of branched-chain amino acids, or BCAAs – essential amino acids that human beings cannot synthesize and must obtain through diet – milk protein serums are widely used to promote growth and stimulate production of muscle mass. This property also makes these serums an important nutritional supplement for people with pathological muscle-depletion conditions.

Milk protein serums also have anti-hypertension and anti-ulcer functions that have been detailed in the literature. However, a recent discovery based on research in rats is that other beneficial properties are added when milk protein serums are hydrolyzed by enzymes (that is, partially decomposed into peptides, each of which is formed by two or more amino acids): a reduction in hyperglycemia and an impact on cell protection and stress reduction.

The discovery was made at the School of Food Engineering’s Laboratory of Protein Sources at Universidade Estadual de Campinas (Lafop-Campinas) during three FAPESP-funded research projects coordinated by Jaime Amaya Farfan: The effect of consumption of hydrolyzed milk serum on the energetic metabolism and redox state of exercising rats, The effect of consumption of milk protein serums on HSP biomarkers and biochemical parameters in rats and The effect of intact and whey protein hydrolysate consumption on glucose transporters 1 and 4 in rats.

The team led by Farfan, which includes the researchers Pablo Christiano Barbosa Lollo (doctoral student), Priscila Neder Morato (doctoral student), Carolina Soares de Moura (master’s student) and Luciana Nisishima (scientific initiation), published two articles in the journal Food Chemistry: A dipeptide and amino acid present in whey protein hydrolysate increase translocation of GLUT-4 to the plasma membrane in Wistar rats and Whey protein hydrolysate enhances the exercise-induced heat shock protein (HSP70) response in rats. Another paper by the team, “Whey protein hydrolysate increases translocation of GLUT-4 to the plasma membrane independent of insulin in Wistar rats,” will be published in PLoS One.

The powerful role of whey protein hydrolysate in activating utilization of glucose was also described by a group of Japanese researchers, after the phenomenon had been observed and detailed by the Unicamp team.

Farfan explained, “The experiments indicate that the ingestion of whey protein, especially whey protein hydrolysate, promotes utilization of blood glucose and glycogen synthesis in the skeletal and cardiac muscles. This explains the anti-hyperglycemic effect of combating diabetes and pre-diabetes.”

Hyperglycemia is characterized by elevated levels of glucose in the blood, at approximately 100 milligrams per deciliter. “In a diabetic or a person with hyperglycemia who is en route to diabetes, the blood glucose level does not decrease with the metabolism, generally because either insulin is lacking or the main glucose transporter (GLUT-1) does not work,” he said.

“Therefore,” Farfan added, “whey protein hydrolysate affords an alternative for removing glucose from the circulation and introducing it into cells to generate energy or to be stored in the form of glycogen.” Glycogen is a polymer formed by successive glucose molecules and stored in the liver and muscles.

This “alternative pathway” consists of activation of glucose transporter type 4 (GLUT-4). “The GLUT-4 molecules linger in intracellular vesicles. After activation, they migrate to the plasma membrane, making them available for glucose capture from the bloodstream and transporting it into cells,” Farfan said.

Activation of GLUT-4 is typical in physical exercise. However, experiments have shown that ingestion of whey protein hydrolysate can also occur under sedentary conditions.

“Without discouraging exercise for active people, these proteins are emerging as a possible alternative for handling hyperglycemia in individuals who, due to health conditions, cannot engage in physical exercise because the effect has proven both substitutive and additive to effect of exercise,” said Farfan.

The researcher and his collaborators found that in rats fed casein (an insoluble milk protein that, when extracted, produces whey) or common whey a certain quantity of GLUT-4 was activated. However, animals fed only whey protein hydrolysate mobilized nearly double the quantity.

“Hyperglycemia is extremely harmful because it means that a very large quantity of a chemical reactant is circulating in the bloodstream,” Farfan explained. “Glucose is an aldehyde, and as such, it tends to chemically modify protein receptors and other molecules it comes in contact with. Modified, these molecules no longer work correctly. Scarring, fatty liver and cirrhosis are some of the consequences.”

Cellular protective activity

The property of cellular protection, which may be associated with the anti-hyperglycemic effect, is due to the stimulus that milk protein serum—and, even more so, whey protein hydrolysate—can give to the concentration of the endogenous protective proteins known as heat shock proteins (HSPs).

HSPs comprise a natural defense mechanism that can protect and repair damage to protein structures. HSPs give cells greater tolerance and resistance to a series of aggressive agents, guaranteeing cellular survival during stressful periods.

According to Farfan, “Certain stress conditions can cause a loss in the original conformation and functionality of very sensitive proteins, such as receptors and transporters. Given their constant surveillance of the correct conformation of polypeptides and proteins, HSPs are also known as chaperones. The increase in the content or expression of HSPs adds cytoprotection or restoration of homeostatic balance.”

Before arriving at an explanation involving HSPs, the researchers found that animals on an exclusive diet of whey protein hydrolysate for a prolonged period of time had normal parameters except in relation to one enzyme, the levels of which were reduced: glutaminase.

“Researching all the literature, we saw that a reduction in glutaminase was a good indication because glutamine is the main source of energy for the intestines. It was to be expected that animals submitted to the stress caused by physical exercise would have increased glutaminase because of the greater demand on the intestines. The fact that glutaminase was reduced suggests that rats fed whey protein hydrolysate felt much less stress from the exhaustive exercise than other groups,” said Farfan. This suggestion was confirmed by monitoring hormones related to stress. From that point, the researchers began to investigate HSPs and stress and anti-stress proteins.

Farfan said, “We saw that there was a similar effect to that observed with GLUT-4. Or, rather: the exercise produces a certain quantity of HSPs, as does a whey protein hydrolysate. When you combine the two things, the effects are complementary. As such, we found an explanation for the anti-stress effect.”

The cytoprotective property of protein hydrolysates accounts for the anti-stress effects in that group of rats, which were exercised to the point of exhaustion and exhibited more physical labor than animals on a casein diet or even a milk protein serum diet. At the same time, the GLUT-4 activation property explains hydrolysates’ muscular glycogen-saving effect on exhausted animals and the synthesis stimulation and glycogen accumulation in sedentary rats.

“With the western blot technique, we proved that whey protein hydrolysates can promote GLUT-4 translocation from inside cells to cell membranes, which are the action sites,” Farfan noted. “Therefore, and supporting the findings with tests on the innocuity of prolonged consumption of protein hydrolysate, we suggest that hydrolysates can activate glucose transportation and utilization in the same manner as exercise.”

As a result of the study’s findings, the researchers now intend to study the effects of protein hydrolysates in humans.