using Glucose Disposal agents? [Archive] - CANADA BODYBUILDING

Praetorian

05-12-2012, 07:26 PM

GDA's increase insulin sensitivity which allows more carbs to be stored as glycogen in muscle tissue than converted to body fat. In essence less insulin is necessary to do the job because the cell becomes more sensitive to it. So you would have less of a chance to become diabetic not more.
P

PS. here is a good read...

The Ultimate Glucose Disposal Agent
By Bill Willis, PHD Candidate

You may have heard about the supplement that John helped design for TrueProtein called the Ultimate Glucose Disposal Agent. It was a very well thought supplement, that is picking up rapidly in popularity. People are reporting eating more and staying leaner, “fuller” looking muscle, and also getting leaner during fat loss phases without harsh stimulants that can rock your adrenal glands over time. Read on for more info.

No matter what your fitness goals are, harnessing the power of insulin is the key to getting there. As a potent inducer of amino acid uptake and protein synthesis, insulin is key to muscle growth and recovery. To be sure, Insulin is the most anabolic hormone in the body, but it’s also a double-edged sword. Insulin also directs the use and storage of glucose from carbohydrates in the diet. Glucose is stored as glycogen in muscle or liver tissue, or as fat, in adipose tissue. Fortunately, we do have some influence as to where insulin directs glucose. Glucose disposal agents (GDAs) help to ensure that carbs are stored as glycogen in hard-working muscles instead of fat. GDAs harness the power of insulin by working with the body, optimizing the response to naturally produced insulin for a leaner, more muscular, and healthier physique.

There are lots of choices for glucose disposal agents out there, and they work through different mechanisms. Ideally, we would “stack” several GDAs together to take advantage of their different, but complementary effects on insulin signaling. The result of this approach is synergy, where the whole is greater than the sum of the parts. (Sort of like 1+1+1 = 10). Getting all these glucose disposal agents together and taking them in the right amounts at the right time can be a pain. Fortunately this has already been worked out in the new glucose disposal agent supplement, The Ultimate Glucose Disposal Agent. The result is a synergistic combination of GDAs that helps to increase glycogen stores for leaner, harder muscles and low body fat.

To fully get a grasp for how and why this new GDA from TrueProtein is Ultimate, we are going to have to dive into the nuts and bolts of insulin signaling, which can get heavy on the technical side. For the non-science dorks out there, I’ll provide a “take home message” after certain sections that sums it up and gives practical information.

Insulin and Insulin Signaling… An Overview

All dietary carbohydrates are broken down into glucose in the small intestine, which is then absorbed into the blood stream. This will either be used as an immediate energy source for ATP synthesis or will be stored, as directed by insulin. Glucose is stored as glycogen in the liver and muscle tissue, or is converted to triglyceride and stored as body fat in adipose tissue. Obviously we want to maximize muscle glycogen storage and protein synthesis in muscle tissue while minimizing fat gain. The problem is that glucose will be stored as glycogen only until glycogen stores (in muscle and liver) are topped off, at which point the excess glucose is converted to fat. Muscle is the major site of insulin-stimulated glucose disposal, which means that any GDA should maximize muscle glycogen storage, which will minimize spillover to fat stores.

Take Home:

A muscle full of glycogen is a big, full, anabolic muscle
Glucose disposal agents can maximize the anabolic effects of insulin while minimizing body fat storage.

Fat Storage and Insulin Sensitivity

Fats are stored in adipose tissue as triglycerides, which consist of three fatty acid molecules with a glycerol backbone. To say that carb intake above a certain point “spills” into fat cells is only half-right; insulin stimulates fat cells to take up glucose all the time, where it is converted to glycerol or fatty acids, both of which are required to form triglycerides which are stored as body fat. Under ideal circumstances, muscle and liver glucose uptake is high, fat glucose uptake is low and only a small amount of insulin is needed to get the job done. No fat is stored under these conditions. The small amount of glucose absorbed by adipose tissue is converted to glycerol; instead of being used to make triglyceride it gets sent back to the liver where it will be used to make more glucose. Under these conditions, we say you are “insulin sensitive”- a small amount of insulin has a big effect. Eat too many carbs (or the wrong kind), and things can change; glucose will only be deposited into muscle and liver tissue until glycogen stores are full; the rest of this excess energy will be turned into fatty acids and stored as triglycerides in adipose tissue. The bigger the insulin response, the more the insulin signaling machinery will become resistant to the effects of more insulin, particularly in muscle tissue. This increases the amount of insulin needed to get the job done to overcome this “insulin resistance”. As a result of insulin resistance, increased insulin levels cause more glucose to be diverted into adipose tissue and stored as body fat. This can happen pretty quickly… Overdo the carbs with just one meal and the big insulin response that is generated will temporarily desensitize muscle insulin receptors, causing glucose to spill over into fat stores. Long-term, especially in people with a genetic predisposition, this same process can lead to obesity and diabetes. There are definitely genetic factors here; leaner people in general tend to be much more insulin sensitive, with lower insulin levels. Likewise, people that have a genetic predisposition to obesity are more likely to be insulin resistant. While we can’t change our genetic makeup, GDAs increase insulin sensitivity which causes more carbs to be stored in muscle tissue as glycogen instead of being converted to body fat.

Take Home:

More insulin = more carbs stored as body fat.
When you are insulin sensitive, glucose is more likely to be stored as glycogen in muscle tissue, rather than body fat.
Overdoing carbs - even in the short-term, can decrease insulin sensitivity and cause fat storage.
Glucose Disposal agents make you more insulin sensitive, promoting muscle growth and glycogen storage while minimizing fat gain from the carbs you eat.

The Nuts and Bolts of Insulin Signaling

To understand what makes the Ultimate Glucose Disposal agent “Ultimate” we will have to briefly dive in to the nuts and bolts of the insulin signaling machinery. Insulin action in target cells (muscle or adipose tissue, for our purposes here) begins when insulin binds to the insulin receptor on cell membranes. This activates the insulin receptor tyrosine kinase activity, which phosphorylates and activates a protein called insulin receptor substrate 1 (IRS-1). In turn, IRS-1 activates two parallel cell signaling pathways, the ERK/MAPK pathway, which activates downstream genes responsible for the growth-promoting effects of insulin, and the PI3K/Akt pathway, which activates glucose transport, protein synthesis, and glycogen synthesis.

Insulin is just the messenger; the real action happens with the protein GLUT4, which gets activated downstream of PI3K/Akt. Upon activation, GLUT4 is sent from the cytosol to the cell membrane, where it acts as a gateway for glucose to enter the cell. The more GLUT4 molecules that are sent to the cell membrane, the more glucose will be allowed to enter the cell. The exact details of how insulin activates GLUT4 translocation and glucose uptake are still being worked out, but the basics here are the key to understanding insulin sensitivity; the less insulin needed to send GLUT4 to the cell membrane for glucose uptake, the more insulin sensitive you are. Likewise, anything that can either directly or indirectly activate GLUT4 translocation will increase insulin sensitivity. The Ultimate Glucose Disposal agent activates GLUT4 by several different mechanisms, resulting in a synergistic increase in insulin sensitivity.

Now that we know a little about how insulin works, why it’s good to be insulin sensitive, and that GDAs can increase insulin sensitivity, it’s time for the million-dollar question: What makes the Ultimate Glucose Disposal Agent so…Ultimate?

To be “Ultimate”, a Glucose Disposal Agent would…

Amplify the effects of insulin: So your body needs to use less. This is the definition of insulin sensitivity… more “bang for your insulin buck”
Have “Insulin mimetic” activity: Able to activate glucose uptake independent of exogenous insulin use.
Reduce inflammation: Inflammation decreases insulin sensitivity.
Optimize oxidation: Too much or too little reactive oxygen reduces insulin sensitivity. The Ultimate GDA would have antioxidant activity to protect from oxidative stress while optimizing reactive oxygen production for maximum insulin sensitivity.
Not be a drug: Drugs are vital for people suffering with diabetes, but their use comes at a cost... dangerous side effects. The Ultimate GDA would be derived from natural ingredients, with no drug-like toxicity issues or side-effects.
Actually Work!!! No smoke/mirrors, or BS…. Promote lean muscle gain and fat loss by making REAL changes in insulin sensitivity in people who already train hard!

How the Ultimate Glucose Disposal Agent Ingredients Synergistically Act to Increase Insulin Sensitivity:

Gymnema Sylvestre
Gymnema Sylvestre is a plant found in central and southern India, tropical Africa, and tropical Australia. The active chemical is gymnemic acid, which is actually a mixture of 12 naturally occurring saponins. GS has a potent effect on insulin sensitivity and glucose disposal, affecting a number of different aspects of insulin signaling. The precise cell signaling pathways that GS activates haven’t been worked out yet by scientists, but there is a large body of evidence for its positive effects on insulin signaling. First and foremost, GS acts to decrease glucose uptake from the small intestine(1). GS also increases peripheral insulin sensitivity (2), and causes big improvements in glucose uptake and glycogen synthesis and in liver and muscle(3). This means that more glycogen is rammed into your muscles after eating carbohydrates, resulting in harder, fuller muscles and less body fat gain. Another nice property of GS is that it actually helps to regenerate damaged pancreatic beta cells (4), which is probably related to its anti-inflammatory effects. While this is more important for diabetics, pancreatic beta cells are the only site of insulin production in the body. It’s always good to take care of these cells! Lose them and you are taking insulin for the rest of your life.

Alpha Lipoic acid
ALA is naturally found in small amounts in muscle meats, heart, kidney, liver, and some fruits in vegetables (5-7), but needs to be supplemented to get enough for its positive effects. First off, ALA is a potent antioxidant, which can neutralize hydroxyl radicals and singlet oxygen, two of the most destructive free radicals (8, 9). The great thing about this stuff is that it is actually neutral against hydrogen peroxide. This is important, because some natural hydrogen peroxide production is needed for optimal insulin sensitivity and muscle growth. ALA can also help to regenerate other endogenous antioxidants such as vitamins C and E (10). In this way ALA optimizes oxidation, protecting cells from oxidative stress while optimizing reactive oxygen production for maximum insulin sensitivity. ALA also increases intracellular glutathione levels, making it a really a potent liver detox agent (11). Like GS, ALA has a potent effect on inflammation which also contributes to its insulin-sensitizing effects. ALA activates multiple pathways downstream of the insulin receptor including Erk/MAPK (12, 13), which activates muscle growth-related genes. ALA has a synergistic effect on muscle glucose uptake by activating GLUT4 (14, 15) via multiple pathways including AMPK (16), PI3K/Akt(17, 18), and by another PI3K/Akt independent pathway(19).This means that ALA fires up cell signaling that leads to muscle growth, insulin sensitivity, and glycogen storage.

*Note on R-ALA vs. ALA:
We have gotten lots of questions related to this so a quick note on the difference between ALA and R-ALA: All alpha lipoic acid is not the same. The alpha lipoic acid molecule has something called a “chiral center”, which means that it can exist in two different confirmations which are mirror images of each other. The best way to understand this is to look at your right and left hand. They are the same, but you can’t superimpose one on top of the other, because they are mirror images. Same deal with chiral molecules; one conformation can be thought of as “right handed” and the other as “left handed”. When synthesized in a lab, chiral molecules usually exist as enantiomeric pairs (a fancy way of saying a molecule exists in both the right-and left-handed conformation). It turns out that alpha lipoic acid is naturally produced in the body, and as with most biological molecules, it usually does not exist as an enantiomer (naturally produced alpha lipoic acid is the “R” form). Alpha lipoic acid commercially available as “ALA” is the enantiomeric mixture (the label will just say “ALA” here). Likewise, commercially available “R-ALA” is the “R” isomer (the “right-handed” form). The R-form is also the form naturally produced in the body. It turns out that the most potent insulin sensitizing effects are linked to the R-form of ALA. Because ALA is a mixture of right-and left-handed forms (R-ALA and S-ALA), taking regular ALA will have some of the insulin-sensitizing effects of pure R-ALA. The equivalent amount of ALA needed to have the same effect of a given dose of R-ALA is debatable. As with most enantiomers such as ibuprofen, the non-active form can often block the effects of the active form. So with ALA, your best-bet is to go with the R-form (naturally The Ultimate Glucose Disposal Agent contains R-ALA).

Vanadyl Sulfate
VS is an “Insulin mimetic” which means it can activate glucose uptake without insulin. As an insulin mimetic, VS is able to bypass the insulin receptor by directly activating IRS-1 and downstream PI3K activity (20, 21). VS has a great track record with type 2 diabetes, where it increases insulin sensitivity and glucose homeostasis (22, 23). Importantly, VS also amps up glycogen synthesis, helping to keep muscles full (24, 25). VS is also a potent GLUT4 activator (23, 26).

Cinnamon Extract (CE)
I could write a book on the positive effects of this stuff, but there are plenty already out there. First off, CE not only helps insulin do its job better, but it has insulin mimetic properties. CE has a big effect on glucose uptake, and can directly increase GLUT4 levels through insulin dependent- and independent mechanisms (27, 28). CE also enhances IRS-1 activation by insulin (29, 30), which increases insulin sensitivity. CE is also a potent anti-inflammatory agent; this is important because excess inflammation can have a big negative insulin sensitivity (27). There is an absolute ton of research on the positive effects of CE on insulin signaling in humans. In diabetics, CE has been shown to decrease fasting glucose, decrease LDL cholesterol (the bad kind), increase HDL cholesterol (the good kind) and to decrease triglycerides (31). In a study on people with metabolic syndrome, CE decreased fasting glucose, systolic BP, and body fat %, while increasing lean mass at the same time(32). Importantly, CE has also been shown to work in normal, healthy people to improve glucose tolerance and insulin sensitivity(33).

Chromium Picolinate
No glucose disposal agent would be complete without the addition of chromium; it’s an essential trace nutrient needed for carbohydrate metabolism. Chromium is another one of the agents that can directly affect insulin sensitivity by activating GLUT4 (34, 35). It has also been shown to be a potent potentiator of insulin signaling in general. Unconfirmed effects of chromium include enhanced interaction of insulin with the insulin receptor, increased pancreatic beta-cell sensitivity, and an increase in the number of insulin receptors. There has been lots of back and forth in the research literature as to whether chromium works or not. In many of the studies where chromium didn’t work, the dose was relatively low. Another factor is that to date, scientists still aren’t sure exactly how the stuff works. Especially with experiments looking at cell signaling, it’s hard to measure an effect if you don’t know exactly what to look for. What we do know is that chromium supports insulin signaling by several known and unknown mechanisms(36), and a deficiency is real bad news for insulin sensitivity. Because of this, no GDA supplement would be complete without chromium.

Biotin
Last but not least, The Ultimate GDA includes biotin, which is a water-soluble B vitamin also known as vitamin H. Biotin is a cofactor that is required by a number of enzymes in the body, including those important for carbohydrate metabolism. Biotin was included in The Ultimate GDA as more of an insurance plan, based on some research that suggests that ALA may actually compete with biotin for absorption, possibly causing a biotin deficiency. There is also evidence that biotin may work synergistically with chromium to improve glucose metabolism (37).

How to use The Ultimate GDA

The great thing about The Ultimate GDA is that it is useful no matter what phase of training you are currently in. If you are in a muscle-gain phase, more calories are needed to grow. The Ultimate GDA is a great supplement to add here, because you want to ensure that those extra calories are being put to good use, not stored as body fat. If you are dieting, the more insulin sensitive you are, the better the diet will work, so The Ultimate GDA is also great for dieting phases. Post-workout is another great time to use The Ultimate GDA, because insulin is a potent inducer of protein synthesis and amino acid uptake. The Ultimate GDA can be used with any meal that includes carbs, where the recommended dosage is 1 serving (2 capsules) per 100g of carbs.
No matter what your specific goals are, it’s never a bad thing to be leaner, healthier, and stronger. The Ultimate GDA, with its synergistic effects on insulin sensitivity, inflammation, and oxidative stress is great addition to any supplement program. Harness the power of insulin with the Ultimate GDA and take your training to the next level!

To purchase this product for 29.99 for a 1 month supply, go to the link listed below. You can also input “meadows” in the discount box, and get an additional discount.

http://www.trueprotein.com/Product_Details.aspx?cid=25&pid=6967

Reference List
Porchezhian E, Dobriyal RM. An overview on the advances of Gymnema sylvestre: chemistry, pharmacology and patents. Pharmazie 2003;58:5-12.

Okabayashi Y, Tani S, Fujisawa T, Koide M, Hasegawa H, Nakamura T, et al. Effect of Gymnema sylvestre, R.Br. on glucose homeostasis in rats. Diabetes Res Clin Pract 1990;9:143-8.

Shanmugasundaram KR, Panneerselvam C, Samudram P, Shanmugasundaram ER. Enzyme changes and glucose utilisation in diabetic rabbits: the effect of Gymnema sylvestre, R.Br. J Ethnopharmacol 1983;7:205-34.

Shanmugasundaram ER, Gopinath KL, Radha SK, Rajendran VM. Possible regeneration of the islets of Langerhans in streptozotocin-diabetic rats given Gymnema sylvestre leaf extracts. J Ethnopharmacol 1990;30:265-79.

Akiba S, Matsugo S, Packer L, Konishi T. Assay of protein-bound lipoic acid in tissues by a new enzymatic method. Anal Biochem 1998;258:299-304.

Packer L, Kraemer K, Rimbach G. Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition 2001;17:888-95.

Wollin SD, Jones PJ. Alpha-lipoic acid and cardiovascular disease. J Nutr 2003;133:3327-30.

Scott BC, Aruoma OI, Evans PJ, O'Neill C, Van d, V, Cross CE, et al. Lipoic and dihydrolipoic acids as antioxidants. A critical evaluation. Free Radic Res 1994;20:119-33.

Devasagayam TP, Subramanian M, Pradhan DS, Sies H. Prevention of singlet oxygen-induced DNA damage by lipoate. Chem Biol Interact 1993;86:79-92.

Biewenga GP, Haenen GR, Bast A. The pharmacology of the antioxidant lipoic acid. Gen Pharmacol 1997;29:315-31.

Han D, Handelman G, Marcocci L, Sen CK, Roy S, Kobuchi H, et al. Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. Biofactors 1997;6:321-38.

Suzuki YJ, Shi SS, Day RM, Blumberg JB. Differential regulation of MAP kinase signaling by pro- and antioxidant biothiols. Ann N Y Acad Sci 2000;899:159-67.

Shi SS, Day RM, Halpner AD, Blumberg JB, Suzuki YJ. Homocysteine and alpha-lipoic acid regulate p44/42 MAP kinase phosphorylation in NIH/3T3 cells. Antioxid Redox Signal 1999;1:123-8.

Treebak JT, Glund S, Deshmukh A, Klein DK, Long YC, Jensen TE, et al. AMPK-mediated AS160 phosphorylation in skeletal muscle is dependent on AMPK catalytic and regulatory subunits. Diabetes 2006;55:2051-8.

Konrad D, Somwar R, Sweeney G, Yaworsky K, Hayashi M, Ramlal T, et al. The antihyperglycemic drug alpha-lipoic acid stimulates glucose uptake via both GLUT4 translocation and GLUT4 activation: potential role of p38 mitogen-activated protein kinase in GLUT4 activation. Diabetes 2001;50:1464-71.

Lee WJ, Song KH, Koh EH, Won JC, Kim HS, Park HS, et al. Alpha-lipoic acid increases insulin sensitivity by activating AMPK in skeletal muscle. Biochem Biophys Res Commun 2005;332:885-91.

Zhang WJ, Wei H, Hagen T, Frei B. Alpha-lipoic acid attenuates LPS-induced inflammatory responses by activating the phosphoinositide 3-kinase/Akt signaling pathway. Proc Natl Acad Sci U S A 2007;104:4077-82.

Shay KP, Hagen TM. Age-associated impairment of Akt phosphorylation in primary rat hepatocytes is remediated by alpha-lipoic acid through PI3 kinase, PTEN, and PP2A. Biogerontology 2009;10:443-56.

Henriksen EJ, Jacob S, Streeper RS, Fogt DL, Hokama JY, Tritschler HJ. Stimulation by alpha-lipoic acid of glucose transport activity in skeletal muscle of lean and obese Zucker rats. Life Sci 1997;61:805-12.

Pandey SK, Anand-Srivastava MB, Srivastava AK. Vanadyl sulfate-stimulated glycogen synthesis is associated with activation of phosphatidylinositol 3-kinase and is independent of insulin receptor tyrosine phosphorylation. Biochemistry 1998;37:7006-14.

Molero JC, Martinez C, Andres A, Satrustegui J, Carrascosa JM. Vanadate fully stimulates insulin receptor substrate-1 associated phosphatidyl inositol 3-kinase activity in adipocytes from young and old rats. FEBS Lett 1998;425:298-304.

Cohen N, Halberstam M, Shlimovich P, Chang CJ, Shamoon H, Rossetti L. Oral vanadyl sulfate improves hepatic and peripheral insulin sensitivity in patients with non-insulin-dependent diabetes mellitus. J Clin Invest 1995;95:2501-9.

Boden G, Chen X, Ruiz J, van Rossum GD, Turco S. Effects of vanadyl sulfate on carbohydrate and lipid metabolism in patients with non-insulin-dependent diabetes mellitus. Metabolism 1996;45:1130-5.

Tamura S, Brown TA, Whipple JH, Fujita-Yamaguchi Y, Dubler RE, Cheng K, et al. A novel mechanism for the insulin-like effect of vanadate on glycogen synthase in rat adipocytes. J Biol Chem 1984;259:6650-8.

Clark AS, Fagan JM, Mitch WE. Selectivity of the insulin-like actions of vanadate on glucose and protein metabolism in skeletal muscle. Biochem J 1985;232:273-6.

Li SH, McNeill JH. In vivo effects of vanadium on GLUT4 translocation in cardiac tissue of STZ-diabetic rats. Mol Cell Biochem 2001;217:121-9.

Qin B, Polansky MM, Anderson RA. Cinnamon extract regulates plasma levels of adipose-derived factors and expression of multiple genes related to carbohydrate metabolism and lipogenesis in adipose tissue of fructose-fed rats. Horm Metab Res 2010;42:187-93.

Shen Y, Fukushima M, Ito Y, Muraki E, Hosono T, Seki T, et al. Verification of the antidiabetic effects of cinnamon (Cinnamomum zeylanicum) using insulin-uncontrolled type 1 diabetic rats and cultured adipocytes. Biosci Biotechnol Biochem 2010;74:2418-25.

Qin B, Polansky MM, Sato Y, Adeli K, Anderson RA. Cinnamon extract inhibits the postprandial overproduction of apolipoprotein B48-containing lipoproteins in fructose-fed animals. J Nutr Biochem 2009;20:901-8.

Qin B, Nagasaki M, Ren M, Bajotto G, Oshida Y, Sato Y. Cinnamon extract (traditional herb) potentiates in vivo insulin-regulated glucose utilization via enhancing insulin signaling in rats. Diabetes Res Clin Pract 2003;62:139-48.

Khan A, Safdar M, Ali Khan MM, Khattak KN, Anderson RA. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care 2003;26:3215-8.

Ziegenfuss TN, Hofheins JE, Mendel RW, Landis J, Anderson RA. Effects of a water-soluble cinnamon extract on body composition and features of the metabolic syndrome in pre-diabetic men and women. J Int Soc Sports Nutr 2006;3:45-53.

Solomon TP, Blannin AK. Changes in glucose tolerance and insulin sensitivity following 2 weeks of daily cinnamon ingestion in healthy humans. Eur J Appl Physiol 2009;105:969-76.

Pattar GR, Tackett L, Liu P, Elmendorf JS. Chromium picolinate positively influences the glucose transporter system via affecting cholesterol homeostasis in adipocytes cultured under hyperglycemic diabetic conditions. Mutat Res 2006;610:93-100.

Chen G, Liu P, Pattar GR, Tackett L, Bhonagiri P, Strawbridge AB, et al. Chromium activates glucose transporter 4 trafficking and enhances insulin-stimulated glucose transport in 3T3-L1 adipocytes via a cholesterol-dependent mechanism. Mol Endocrinol 2006;20:857-70.

Vincent JB. Elucidating a biological role for chromium at a molecular level. Acc Chem Res 2000;33:503-10.

Albarracin CA, Fuqua BC, Evans JL, Goldfine ID. Chromium picolinate and biotin combination improves glucose metabolism in treated, uncontrolled overweight to obese patients with type 2 diabetes. Diabetes Metab Res Rev 2008;24:41-51.