does creatine lower blood sugar

 

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Summary

The aim of this examine was to analyze the impact of oral creatine
supplementation on muscle GLUT4 protein content material and complete creatine and
glycogen content material throughout muscle disuse and subsequent coaching. A double-blind
placebo-controlled trial was carried out with 22 younger wholesome volunteers. The
proper leg of every topic was immobilized utilizing a forged for two weeks, after
which topics participated in a 10-week heavy resistance coaching program
involving the knee-extensor muscle groups (three classes per week). Half of the
topics obtained creatine monohydrate dietary supplements (20 g each day in the course of the
immobilization interval and 15 and 5 g each day in the course of the first 3 and the final 7
weeks of rehabilitation coaching, respectively), whereas the opposite 11 topics
ingested placebo (maltodextrine). Muscle GLUT4 protein content material and glycogen
and complete creatine concentrations had been assayed in needle biopsy samples from
the vastus lateralis muscle earlier than and after immobilization and after 3 and 10
weeks of coaching. Immobilization decreased GLUT4 within the placebo group (-20%,
P < 0.05), however not within the creatine group (+9% NS). Glycogen and complete creatine had been unchanged in each teams in the course of the immobilization interval. Within the placebo group, throughout coaching, GLUT4 was normalized, and glycogen and complete creatine had been secure. Conversely, within the creatine group, GLUT4 elevated by ∼40% (P < 0.05) throughout rehabilitation. Muscle glycogen and complete creatine ranges had been increased within the creatine group after 3 weeks of rehabilitation (P < 0.05), however not after 10 weeks of rehabilitation. We concluded that 1) oral creatine supplementation offsets the decline in muscle GLUT4 protein content material that happens throughout immobilization, and a pair of) oral creatine supplementation will increase GLUT4 protein content material throughout subsequent rehabilitation coaching in wholesome topics.  

RESEARCH DESIGN AND METHODS – “does creatine lower blood sugar”

Topics. A complete of 13 males and 9 ladies, aged 20-23 years, gave
their knowledgeable written consent to take part within the examine. They had been
instructed to abstain from taking any treatment and to keep away from making any
modifications of their typical bodily exercise degree and different residing habits throughout
the interval of the examine. Nonetheless, three of the ladies had been taking oral
contraceptives throughout the examine. The native ethics committee
accepted the examine protocol.

Examine protocol. A double-blind examine was carried out over a 12-week
interval. At first of the examine, topics had been systematically assigned to
both a creatine or a placebo group based mostly on quadriceps muscle
cross-sectional space and maximal isometric knee-extension torque to acquire two
teams of comparable distribution (P.H., B.O.E., M. Van Leemputte, B.U., P.L.G.,
V. Labarque, S. Dymarkowski, P. Van Hecke, E.A.R, unpublished observations).
After baseline measurements had been taken, a lightweight polyester forged, extending
from groin to ankle, immobilized every topics’ proper leg at a knee angle of
∼160° for two weeks. Thereafter, the forged was eliminated, and the topics
underwent a standardized 10-week rehabilitation program. Every coaching session
consisted of 4 sequence of 12 unilateral knee-extensions on a knee-extension
equipment, at a workload of 60% of maximal isometric knee-extension torque and
at a charge of three classes per week. Maximal knee-extension torque was
measured at a 90° knee-angle at the beginning of every session utilizing a
calibrated power transducer. Throughout the remaining 7 weeks of the coaching interval,
the sequence of 4 unilateral knee-extensions was elevated to 6. All
coaching classes had been supervised by one of many investigators. Throughout
immobilization, the creatine group obtained 5 g creatine monohydrate 4
instances per day, whereas the placebo group obtained placebo dietary supplements (5 g
maltodextrine, 4 instances per day). Throughout the coaching interval, creatine and
placebo supplementation was diminished to five g thrice per day from week 1 to
3 after which to a single 5-g each day dose from week 4 to 10. The creatine
dietary supplements had been flavored by the addition of citrate (60 mg/g creatine) and
maltodextrine (940 mg/g creatine), whereas the placebo group ingested
maltodextrine containing citrate (40 mg/g maltodextrine). Creatine and placebo
powders had been an identical in style and look. Earlier than and after 2 weeks of
immobilization, and after 3 and 10 weeks of rehabilitation, a percutaneous
needle biopsy from the vastus lateralis muscle was obtained. The final coaching
session preceded muscle sampling by no less than 48 h. As well as, the topics
obtained a standardized dinner (855 kcal, 47% carbohydrate, 25% fats, and 28%
protein) the night earlier than and a standardized breakfast (320 kcal, 65%
carbohydrate, 15% fats, and 20% protein) the morning of muscle sampling. To
acquire every muscle biopsy, an incision was made by means of the pores and skin and muscle
fascia underneath native anesthesia (2-3 ml 1% lidocaine). Throughout classes 2-4, the
incision was made both proximal or distal to the incision made at an earlier
session. On elimination from the limb, a bit of every muscle biopsy was
instantly blotted and cleaned from seen connective tissue, quickly frozen
in liquid nitrogen, and saved at -80°C for subsequent biochemical and
immunochemical analyses.

Biochemical and immunochemical analyses. The biopsy samples had been
first freeze-dried, then washed twice in petroleum ether to take away fats, and
lastly dissected freed from the remaining seen blood and connective tissue. A
fraction of every pattern was pulverized, and the powdered extracts had been used
for spectrophotometric dedication of glycogen and free creatine and
phosphocreatine concentrations
(18). One other fraction was
used for GLUT4 dedication. An aliquot of the freeze-dried muscle was
homogenized (Polytron) for 30 s on ice in a buffer with the next
composition: 150 mmol/l NaCl, 1% NP4O, 0.5% deoxycholate, 0.1% SDS,
and 50 mmol/l Tris, pH 8. The homogenate was incubated on ice for 1 h and spun
for 15 min at 13,000g, and the supernatant (extract) was collected
for evaluation. Then, 100 μg of the extract had been resolved by SDS-PAGE earlier than
electroblotting to polyvinylidine fluoride membranes. GLUT4 proteins had been then
detected by incubation in Trisbuffered saline with Tween (150 mmol/l NaCl, 50
mmol/l Tris, and 0.1% Tween 20) after blocking in 1% bovine serum albumin with
a selected goat polyclonal antibody towards the 13 COOH-terminal amino acids
of GLUT4. Lastly, GLUT4 was visualized by an alkaline phosphatase-labeled
antibody and quantified on a phosphoimager (STORM; Molecular Dynamics,
Sunnyvale, CA).

Information evaluation. Information are means ± SE. Muscle complete creatine
focus was calculated because the sum of free creatine and phosphocreatine.
Therapy results (creatine versus placebo) had been evaluated by a two-way
evaluation of variance, which was covariate adjusted for the baseline values
(Statistica; Statsoft, Tulsa, OK). Along with these main analyses, we
did a one-way evaluation of variance to check the values after immobilization
and rehabilitation with the corresponding baseline values inside every group.
The statistical analyses of the GLUT4 information had been carried out on the uncooked information
(densitometric counts). P < 0.05 was thought-about statistically important.  

RESULTS

Muscle GLUT4 content material. Muscle GLUT4 concentrations had been expressed
relative to the corresponding baseline values that had been set equal to 1
(Fig. 1). Muscle GLUT4 content material
at baseline was comparable between the teams. Within the placebo group, 2 weeks of
immobilization decreased GLUT4 content material on a median of twenty-two% (range-10 to -35%,
P < 0.05). Conversely, within the creatine group, muscle GLUT4 protein was secure (+9% NS). Within the placebo group, the rehabilitation coaching restored muscle GLUT4 content material inside 3 weeks to the baseline worth, the place it remained. Nonetheless, within the creatine group, muscle GLUT4 content material progressively elevated in the course of the 10-week rehabilitation interval to a price that was ∼40% increased than within the placebo group on the finish of the examine (P < 0.05). Muscle glycogen. The preliminary muscle glycogen focus was 407 ± 43 mmol/kg dry weight (DW) within the placebo group versus 379 ± 19 mmol/kg DW within the creatine group (NS) (Fig. 2). Immobilization did not change muscle glycogen focus in both group. Nonetheless, in the course of the preliminary 3 weeks of rehabilitation coaching, muscle glycogen markedly elevated within the creatine group (P < 0.05), whereas it didn't considerably change within the placebo group. Thus, after 3 weeks, muscle glycogen focus was increased (P < 0.05) within the creatine group (660 ± 70 mmol/kg DW) than within the placebo group (520 ± 60 mmol/kg DW). Nonetheless, in the course of the remaining 7 weeks of rehabilitation coaching, muscle glycogen reverted to baseline values in each teams. Muscle creatine content material. The muscle phosphocreatine and free creatine concentrations at baseline had been comparable between each teams (Desk 1). Throughout immobilization, phosphocreatine focus decreased to ∼15% under the baseline worth within the placebo group (P < 0.05). This lower was negated by creatine supplementation (P < 0.05). Within the placebo group, muscle phosphocreatine focus returned to the preimmobilization baseline degree inside the preliminary 3 weeks of the rehabilitation interval, after which it remained secure. Then again, within the creatine group, in contrast with the placebo group, the muscle phosphocreatine focus elevated to ∼12% above baseline worth after 3 weeks of rehabilitation (P < 0.05). Nonetheless, this improve above baseline in phosphocreatine was reversed throughout the ultimate stage of the rehabilitation interval. All through the examine, the muscle free creatine concentrations weren't considerably totally different between the placebo and the creatine teams. Within the placebo group, muscle complete creatine focus was not considerably modified in contrast with the baseline worth throughout both immobilization or rehabilitation. But within the creatine group, in contrast with the placebo group, the muscle complete creatine focus was increased on the finish of the immobilization interval, in addition to after 3 weeks of rehabilitation (P < 0.05). Nonetheless, together with the declining muscle phosphocreatine ranges, muscle complete creatine returned to baseline by the top of the examine.

 

DISCUSSION

Our examine investigated the affect of creatine supplementation on muscle
GLUT4 content material and glycogen and complete creatine concentrations in wholesome
topics throughout 2 weeks of voluntary leg immobilization adopted by 10 weeks
of rehabilitation coaching. Our information are the primary to point out that creatine
supplementation prevents the lack of GLUT4 protein throughout muscle disuse and
will increase muscle GLUT4 content material above regular ranges throughout subsequent
rehabilitation. Moreover, muscle glycogen focus was elevated
in the course of the preliminary levels of the creatine supplementation.

Glucose transport throughout the plasma membrane is the rate-limiting step for
glucose metabolism. Therefore, muscle GLUT4 content material is a main determinant of
insulin-stimulated muscle glucose uptake and metabolism
(16). Thus, rising muscle
GLUT4 content material by transgenic overexpression or by elevated contractile
exercise enhances maximal insulin-stimulated muscle glucose uptake.
Conversely, decreasing the content material of GLUT4 by GLUT4 knockout, denervation, or
getting older impairs insulin-mediated muscle glucose uptake
(19). Our information, due to this fact,
recommend that creatine supplementation in people might improve insulin
sensitivity by rising muscle GLUT4 content material.

During the last decade, substantial proof has accrued to point out that
endurance train coaching elevates muscle GLUT4 content material and
insulin-stimulated glucose uptake in each wholesome
(17,20,21,22,23,24,25,26,27,28)
and insulin-resistant muscle groups
(29,30).
On this respect, the present examine exhibits that in wholesome people, a low
quantity (3 weekly classes) of reasonable resistance coaching (60% of 1
repetition most [RM]), in distinction with endurance coaching
(23,24,25,26,
28) or each day maximal
resistance coaching (31), is
not a ample stimulus to extend muscle GLUT4 content material. Ten weeks of
rehabilitation coaching per se didn’t improve muscle GLUT4 content material above the
baseline degree (Fig. 1).
Nonetheless, the identical coaching routine along with oral creatine
supplementation resulted in a marked improve of muscle GLUT4 protein content material.
Actually, our observations point out that oral creatine supplementation can
most likely improve GLUT4 protein content material in skeletal musculature unbiased of
train coaching. Consistent with earlier observations
(17,20,21,22,31,32),
muscle deconditioning by immobilization within the placebo topics diminished GLUT4
protein content material (∼20%). Nonetheless, on the finish of the immobilization
interval, GLUT4 content material within the creatine group tended to extend by ∼10%,
which resulted in a 30% distinction in muscle GLUT4 between placebo and
creatine supplementation within the absence of a coaching stsore, it’s affordable
to conclude that creatine supplementation can improve GLUT4 protein content material
in human musculature throughout episodes of both diminished or elevated bodily
exercise.

Based mostly on the present data, it’s troublesome to disclose the molecular
foundation for the rise in muscle GLUT4 content material that happens throughout creatine
supplementation. It has not too long ago been noticed in rats that short-term
administration of amino-imidazole-4-carboximide riboside, an AMP-activated
protein kinase (AMPK) agonist, will increase muscle GLUT4 content material
(33). Creatine administration
that will increase AMPK exercise by reducing the phosphocreatine-to-creatine
ratio (34) might, thus, clarify
the rise in GLUT4 protein content material within the creatine group. And but, in each
teams the phosphocreatine-to-creatine ratio decreased to the identical diploma
throughout immobilization and remained under the baseline worth in the course of the
subsequent rehabilitation interval. Moreover, it has not too long ago been proven that
the creatine kinase (CK) and AMPK enzymes colocalize in muscle cells
(34). In accordance with the
prevailing opinion, in skeletal muscle, such coupling ought to serve to suppress
muscle AMPK exercise by sustaining excessive native ATP:AMP and
phosphocreatine-to-creatine ratios in situations of mobile stress, corresponding to
contractions (35). If
something, this inhibitory motion is enhanced by the elevated muscle
phosphocreatine focus established in the course of the creatine supplementation
(Desk 1). Thus, proof for a
potential creatine-induced improve in AMPK exercise has not been discovered.
Alternatively, there may be substantial proof to recommend that mobile
hydration standing is a vital issue controlling mobile protein turnover
(36), which in muscle cells,
excluding the contractile proteins, might contain different proteins vital to
power homeostasis, corresponding to GLUT4. Creatine is cotransported with Na ions
throughout the sarcolemma, which initiates inflow of Cl- and water to
stability electroneutrality and osmolality
(11). The ensuing improve
of cell quantity might, in flip, act as an anabolic proliferative sign, which
includes activation of the mitogen-activated protein kinase (MAPK) signaling
cascade that performs a pivotal function in muscle protein synthesis regulation
(37,38).
It’s warranted to additional discover the potential function of intracellular creatine
content material in modulating the concerted actions of CK, AMPK, and MAPK in
regulating GLUT4 synthesis and degradation in muscle cells.

The majority of glucose within the human physique is saved as muscle glycogen. The
presence of a excessive muscle glycogen focus, on the whole, signifies
satisfactory insulin stimulation of muscle glucose uptake and glycogen synthesis.
Moreover, a excessive muscle glycogen focus is a prerequisite for
optimum endurance train efficiency
(39). Robinson et al.
(8) have not too long ago demonstrated
that carbohydrate consumption along with creatine supplementation resulted
in higher postexercise muscle glycogen resynthesis than carbohydrate consumption
alone. Accordingly, within the present examine, in the course of the preliminary 3 weeks of
rehabilitation coaching, muscle glycogen focus elevated by ∼30%
within the placebo group, whereas a threefold higher improve occurred within the
creatine group. This higher-than-average glycogen degree, established by
creatine supplementation (>650 mmol/kg DW)
(Fig. 2), corresponds with
widespread glycogen ranges in younger wholesome topics after glycogen
“supercompensation”
(39). Provided that no dietary
directions had been administered to the topics, our findings recommend that the
addition of creatine supplementation to a normal weight loss program might finally consequence
in a postexercise increment of muscle glycogen focus much like that
discovered after a classical carbohydrate-enriched glycogen supercompensation
dietary protocol (39).
Curiously, after 5 weeks of creatine supplementation, the rise of
muscle glycogen content material vanished, regardless of continued creatine supplementation.
Actually, throughout each immobilization and rehabilitation, the sample of muscle
glycogen modifications carefully mimicked the fluctuations of muscle complete creatine
content material (Desk 1)
(Fig. 2). On this respect, Low
et al. (40) have supplied
clear proof that osmotic swelling of muscle cells is a potent stimulus to
muscle glycogen synthesis. The 30 mmol/kg DW improve of muscle complete
creatine, established after 3 weeks of coaching within the creatine group, was
due to this fact most likely ample to induce a level of cell swelling essential to
improve insulin-stimulated glycogen synthesis
(40,36).
If such an osmotic set off mechanism certainly regulates insulin motion on
glycogen synthesis throughout creatine supplementation, then the lower in
muscle creatine content material past 3 weeks of coaching may additionally clarify the
concurrent lower within the muscle glycogen storage. The mechanism behind the
lower in muscle creatine content material in the course of the remaining stage of the examine,
regardless of continued creatine ingestion at a charge presumed to be ample for
sustaining an elevated muscle creatine content material (5 g/day), is unclear
(2,41).
Research in rats have demonstrated that long-term high-dose creatine feeding
induces a downregulation of muscle complete Na-creatine cotransporter protein
content material (42). As well as, the
low creatine transporter content material in failing human myocardium has been discovered to
be related to a lower in intracellular creatine storage
(43).

In conclusion, the present findings present sturdy proof to recommend that
1) oral creatine supplementation can offset the decline of muscle
GLUT4 protein content material in skeletal musculature throughout disuse atrophy, and
2) oral creatine supplementation will increase GLUT4 content material throughout
subsequent rehabilitation coaching. Based mostly on the current findings, it’s
warranted to judge the potential of long-term creatine supplementation as a
technique to stop or deal with illness situations characterised by peripheral
insulin resistance.

 

“does creatine lower blood sugar”