The Taming of Insulin - How to make it work for you
Found a great article I would like to share!
The Taming of Insulin
How to make it work for you
by Cy Willson
Insulin's effects are the center of discussion around every dinner table in the world. Every man, woman and child knows about the importance of insulin and it's various roles. Why, moms even make sure to pack lunches containing the precise amounts of macros to provide a steady and stable insulin release so their little kiddies can focus and learn in school. Why, just last night, presidential candidate Al Gore promised that three billion tax dollars will be allocated to prevent the resistance to insulin in America!
Okay, okay, maybe I'm exaggerating just a little! Maybe the general public doesn't view insulin sensitivity and the effects of insulin in the same light as we do. However, for bodybuilders, the above doesn't seem so far fetched. We know how important insulin is to us. We know it's one of the most important hormones in the body in terms of our bodybuilding efforts. Is it just as important as my own beloved hormone, Testosterone? Well, as much as I hate to say it, yes.
The reason why insulin is so important is because it's so versatile. It's a hormone that must be manipulated, regardless of the person. Whether you have a hard time gaining muscle or dropping fat, insulin can be a very powerful friend or foe. For those trying to gain muscle mass, spiking insulin levels, while insulin sensitivity is high, can provide a tremendous amount of anti-catabolism in the presence of amino acids. This can, of course, lead to a large increase in muscle mass. This is also one of the reasons many pro bodybuilders use exogenous insulin.
On the other hand, insulin resistance can cause a tremendous amount of fat storage. For someone trying to drop body fat, having muscle tissue that's very sensitive to insulin's effects can be very important. Otherwise, losing fat can be extremely difficult. Not only can insulin affect the "golden pair," i.e. muscle gain and fat loss, but it can also affect other hormones as well. It can affect just about every hormone there is, including Testosterone.
So, what brings about insulin resistance? Well, one of the main contributing factors is the GI or glycemic index of a food. Chronic consumption of foods that have a high GI, and consequently cause a large release of insulin, will cause the insulin receptors to become less receptive to insulin. This is where you begin to run into problems, such as: increased hunger, an increased chance of coronary heart disease, decreased fat usage, increased aldosterone (the hormone that causes water retention), increased cortisol, decreased growth hormone, a deficiency of chromium, increased homocysteine levels (a risk factor for coronary artery disease), decreased IGF-1, increased SHBG (sex hormone binding globulin), and decreased Testosterone.(1,2,3,4,5,6,7,8,9,10) AAAAY! No!
To prevent all of these horrible things caused by insulin resistance, a diet consisting of low GI foods can decrease insulin resistance.(11) This is one reason why low carb diets are all the rage here lately. For a more complete review of the GI and some food listings, check out this site.
In general, though, any type of carb that is highly processed has a terribly high GI. So, if it comes in a bag or a box, chances are, you should avoid it.
Because of all the affects that insulin has on both fat loss and muscular gains (as well as health and hormones) I'm going to reveal to you the best ways to become and/or stay sensitive to insulin. First, we'll start with dietary manipulations, then supplements, and finally, we'll look at drugs.
Diet: Put Down That Rice Cake, Fatty!
Before we get started, I'd like to list the benefits of controlling glucose levels by eating low GI foods. It would be easy enough to assume that whatever insulin resistance may cause, insulin sensitivity would produce the opposite. The most interesting benefits would be increased IGF-1, increased Testosterone, increased fat utilization, and for you health crazed guys, decreased LDL, increased HDL levels, and even more important, increased Glutathione levels.(8,12,13,14,15,16) Glutathione is our body's own natural antioxidant. Very potent stuff!
Okay now, let's get down to business! I know there are a lot of foods that can be classified as having a low GI. However, there are some sources of macronutrients that reign far superior to others in terms of how they affect insulin sensitivity.
Fat
We know that saturated fat and trans-fatty acids should be avoided as much as possible because of their detrimental effects on insulin sensitivity.(17,18) So now, the only question is which type of fat would be best to not only lower the GI of other foods, but to also increase insulin sensitivity.
The first type of fat that has beneficial effects beyond just slowing down the rate of digestion, is none other than monounsaturated fat. This particular fat has been shown to improve glucose metabolism and to lower LDL levels to a further extent when compared to polyunsaturated fat.(19,20) It was also shown to decrease insulin and blood pressure. Rich sources of monounsaturated fat include peanuts and pistachios.
Now, don't jump to conclusions and say that I told you to stop consuming polyunsaturated fats rich in omega-6 fatty acids. They are indeed very important and we need them; however, this is the type of fat that most people typically consume large quantities of already and consequently increase their chances of becoming insulin resistant. You see, consuming this type of fat (in large quantities, for extended periods of time) is what can cause problems. It's still far better than saturated fats and trans-fatty acids, though.
The last type of fat is also polyunsaturated, but instead, it's rich in omega-3 fatty acids. These are, by far, the most superior in terms of their direct effects on insulin sensitivity. Including this type of fat in your diet can prevent insulin resistance, improve insulin sensitivity, reduce insulin and glucose levels, and decrease protein degradation. (21,22,23,24,25) It's likely that omega-3's accomplish these feats by modifying the phospholipid components in the skeletal muscle membrane, possibly making it more permeable to glucose. Rich sources are fish oil, flax, and walnuts. When adding any of these fats to your diet, try to get in a minimum of 4-6 grams per meal.
Carbohydrates
When carbs are concerned, we must be very careful, as this is the macro that can have the most dramatic affect on our insulin levels and consequently, how "sensitive" to the effects of insulin our tissues remain.
You probably know that sugars are usually the first thing you should avoid when trying to lower insulin resistance, but one sugar can actually benefit you when consumed in sane amounts. That's right, my favorite, fructose. It was shown to increase insulin sensitivity by 34% in diabetic patients.(26) It also has a lot of other benefits that I've already discussed in my article called The Forbidden Fruit.
We all know that it's also important to consume insoluble fiber in order to slow digestion and thus lower the GI of our food. Common sources are oat bran, oatmeal, veggies, and certain fruits. However, soluble fibers can also provide some benefit to us as well. One such fiber would be guar gum. Taking 5-7 grams three times daily with meals can significantly reduce the rate at which glucose enters the bloodstream, thereby leading to a reduction of insulin levels and an increase in sensitivity.
protein
In terms of what type of protein to consume, there really isn't any conclusive evidence that one type will significantly differ from another in terms of an insulin release. However, when trying to create a meal with an extremely low GI, it would make more sense to use something like casein that has a slower release of amino acids than something like whey (when used alone). This way you'll create a meal that allows for the most stable release of amino acids and glucose.
Putting it all Together
When trying to combine foods in order to create the lowest GI possible and create a steady environment for muscle growth, energy levels, and fat usage, consider the following: Try using a slow digesting protein, such as casein. Then, use a combination of fats like omega-3, omega-6, and monounsaturated sources, ideally at each meal. Lastly, if you want to use a sweetener, use fructose, along with some type of fiber like guar gum in order to slow digestion even further.
As an interesting tidbit, what types of foods you consume can also have an affect on your endogenous Testosterone levels. In fact, it's been demonstrated that when glycemic control was improved in men, Testosterone and its metabolites increased to a significant degree.(12) It's also been shown that HDL levels have a positive effect on T-levels as well.(27) Therefore, increasing the type of fat that raises HDL the most (monounsaturated) would lead to an increase in Testosterone. Why is it so important to increase T-levels (aside from the usual reasons)? Well, it's been shown that low endogenous levels of Testosterone may play a role in the development of insulin resistance.(28)
Are You Insulin Resistant?
Since there have been a lot people asking me for tips on how they can tell if they're insulin resistant, I've come up with a few quick tests. Now, don't get me wrong here, these aren't by any means 100% accurate indicators of insulin sensitivity. They may, however, tell you if you're higher up the scale in terms of insulin resistance.
It's been shown that insulin acts as a vasodilator, causing the blood vessels and vascular tissue to expand and relax.(29) So, it can be assumed that if you're insulin resistant to a significant degree, then your veins may not come to the surface very well after ingesting some type of carbohydrate. This is because the receptors aren't allowing insulin to dock. (Of course, if you're fat, you won't see too many veins anyway.) It's also known that a large increase in blood glucose levels will cause an increase in insulin as well. If muscle tissue is resistant to insulin, then the normal hypoglycemic "bonk" or blood glucose drop that causes drowsiness won't occur.
Combining these two ideas together, I came up with this test: In the morning, before consuming anything else, take in some type of high GI food, like white bread or anything with a GI above 100. Then, for about the next 20 minutes to an hour, see how you respond. If you notice an increase in how pumped your muscles feel and your veins come to the surface, and you start to feel drowsy, then it's likely that your insulin sensitivity is high (and that's good.)
If, however, these things don't occur, it's likely that you may at least be insulin resistant to a moderate degree. If you are, try the foods and tips above. Don't waste time. It's been shown that consuming a low GI meal can improve insulin sensitivity and lower triglyceride levels in only one day!(30)
The Supplement Arsenal!
Not only can the following compounds exert those awesome effects in manipulating insulin and insulin sensitivity, thereby increasing muscle mass and decreasing body fat, but some of them possess some pretty potent antioxidant properties. So, they're actually healthy for you too!
Biotin
While biotin may not be new to either you or your body (as your body already makes some), it has some pretty cool effects on insulin sensitivity, and consequently, on blood glucose levels and control. In a couple of studies, results indicated that biotin may have the ability to act directly on the insulin secreting function of the pancreatic beta cells, the ones that secrete insulin.(31,32) In one study, glucose metabolism was significantly improved, as was insulin sensitivity. These types of results were seen with dosages of around 9-16 milligrams per day.
Vitamin E
Good ol' vitamin E. It's been shown to be great for a number of things, especially its role as an antioxidant. However, in one study, ten healthy, human subjects and fifteen non-insulin dependent diabetics were given 1,350 IU per day for four months. In both healthy and diabetic subjects, vitamin E supplementation was shown to improve glucose tolerance and insulin sensitivity.(33) This is yet another reason to start taking vitamin E if you aren't already doing so. A dosage of around 800-1400 IU should be sufficient.
Magnesium
Yep, there's no limit to what magnesium can do. I make mine go to the clubs and pick me up some hot ladies, which saves me a lot of time! The problem here is that people aren't consuming enough in their diet or are supplementing with terribly absorbed forms, rather than aspartate or another Krebs cycle intermediate. Magnesium has some profound effects on insulin and glucose metabolism. In fact, it was found that insulin-mediated glucose disposal was decreased in normal human subjects with relatively low plasma magnesium levels.(34)
It also improved glucose metabolism and when combined with vanadyl, it had a synergistic effect on improvement of both glycogen synthesis and insulin sensitivity.(35, 36) As far as dosages, take around 350-600 milligrams of the aspartate form per day, but make sure not to consume it with any calcium.
Zinc
Yep, not only does zinc play an integral part in sex hormone production, but it also plays many roles in insulin utilization, secretion, and synthesis. It was even shown to improve insulin levels in Type I and Type II diabetics.(39) Since it's just an overall important mineral, it should be supplemented into the diet at around 20-30 mg per day. Just make sure to get the aspartate form and never take it with a phytate-containing fiber, as it binds to the zinc and basically renders it useless. (By the way, if you're taking a quality ZMA supplement from a company like Twinlab, Biotest, or EAS, then you've got the zinc and magnesium thing covered. According to Victor Conte, the scientist who formulated the stuff, other companies such as Met-Rx, Designer protein and Optimum Nutrition are not selling "authentic" ZMA and therefore, it may not be as bioavailable as the real stuff.)
Potassium
Potassium supplementation has been shown to improve insulin sensitivity, responsiveness, and secretion.(37,38) While it's commonly found in foods, you could still benefit from some additional supplementation, just don't get crazy and get some prescription K+ salts. As far as dosages go, 1-2 grams is enough, since going overboard on K+ supplementation can be dangerous and can lead to some nasty and potentially deadly side effects.
Alpha Lipoic Acid
ALA has been shown to be both water and fat soluble, as well as having potent antioxidant effects. Furthermore, it's had some pretty astounding affects on both insulin sensitivity and glucose disposal.(40, 41) It's also unique in that it's been shown to increase glucose storage in muscle tissue, and not in adipose tissue. Therefore, it seems to increase sensitivity in muscle tissue only. Take around 600 mg per day in divided dosages.
Taurine
This amino acid is quite necessary for muscle tissue and has actually been shown to increase insulin sensitivity and lower the amounts of intra-abdominal adipose tissue.(42) That's the fat underneath your abs that some doctors call "heart attack fat." Not only this, but taurine possesses some anti-catabolic properties as well. I can't give exact dosages at this time, but around 2-6 grams should be sufficient.
Vanadyl Sulfate
While this mineral has been in some bodybuilders' cupboards for years because of it's "real world" effects on getting a pump, it's fallen by the wayside in the past few years. This is probably because of the "inconclusive" evidence as to whether it works or not. Although it was found recently that vanadyl doesn't modify the actions of insulin to stimulate glycogen synthesis, it does improve glucose utilization.(43) It was therefore concluded that vanadyl must act at other steps of insulin action, which would explain the lack of evidence for modifying glycogen storage. I'd say that if it works for you, keep using it. The dosage is around 30mg per day.
The Flavonoids — Epicatechin and Quercetin
While these plant derived flavonoids may be somewhat familiar to some of you for their super potent antioxidant properties, they possess some powerful effects on insulin as well. First, epicatechin was found to have insulin-like activity, and also was found to reduce glucose levels in a similar fashion to the drug metformin!(44, 45) It was also shown to possess antihyperlipidemic properties in another study, meaning it reduces blood fats.(46)
That's some potent stuff, but wait 'till you hear about quercetin! When islets of Langerhans (a type of tissue that partially composes the pancreas and secretes insulin and glucagon directly into the bloodstream) were exposed to either epicatechin or quercetin, insulin release was enhanced by approximately 44-70%!(47) Here's the best part, though. In one study, quercetin selectively inhibited the insulin stimulating effects on glucose transport, oxidation, and it's incorporation into lipids, decreasing lipogenesis by 50%!(48) In other words, it blocked lipogenesis (fat production) caused by insulin and insulin mimicking agents! Now that's impressive!
As far as sources for these flavonoids, grape seed extract or bilberry at 800-2,000 mg per day, is rich in quercetin — 300 mg of green tea extract per day contains enough epicatechin. On a side note, quercetin has been shown to bind at the estrogen receptor and may exert some estrogenic effects. So, you'll need to weigh the evidence yourself and decide whether it's for you.
Momordica Charantia
This fruit, otherwise known as bitter melon, contains a mixture of sterols that possess super potent hypoglycemic properties. In fact, it's more potent than the oral hypoglycemic drug, Tolbutamide.(49) In one study, after two hours of an oral glucose load of 75 grams, 86% of patients given the extract showed a hypoglycemic effect.(50) It was also shown to increase the rate of glycogen formation by 4-5 times. This was attributed to an increase in glucose utilization.(51, 52, 53) If you want to use it, take 1-3 150 mg capsules per day.
The Drugs!
Now for those of you who'd like to take advantage of insulin and the benefits of being sensitive through drug use, I've compiled the following list.
Acetohexamide
This is a derivative of sulfonylureas. Sulfonylureas are compounds that stimulate the islet tissue on the pancreas to synthesize and release endogenous insulin. In general, for those who are insulin resistant, these aren't very beneficial, as they only increase insulin levels to a higher degree. Acetohexamide, however, is unique in the sense that it can increase insulin sensitivity on insulin receptors and improve peripheral utilization of insulin.
Acarbose
This is an alpha-glucosidase inhibitor. This means that it's able to prevent sugars such as maltose and sucrose from being broken down. It works by prolonging the absorption of carbohydrates. It's been shown to decrease somatostatin levels, which theoretically, could lead to an increase in GH. It's also been shown to decrease triglycerides as well as improve the ratio of LDL to HDL.
Benfluorex
This is a derivative of the anoretic drug, Fenfluramine. It works similarly to metformin by increasing insulin sensitivity in peripheral tissues. It also has a slight appetite suppressant effect and can decrease cholesterol while increasing HDL levels.
Glyburide
This drug differs from others in that it may increase the number of insulin receptors resulting in increased insulin sensitivity.
Clofibrate
While the new compounds being used to treat insulin resistance (called glitazones) have proven to be quite effective, another class referred to as fibrates (currently used for their antilipidemic properties) may prove to be just as effective in terms of increasing sensitivity while not resulting in a gain of body fat, and possibly even reducing it. Clofibrate, also known as Atromid-S, could prove to be a rival to metformin. However, to my knowledge, this has only been found in animal models. So, stay tuned and be on the look out!
Metformin
This drug is my personal favorite. Why? Well, the problem with most other insulin sensitizing drugs is that they don't work selectively to sensitize only muscle tissue. Their increased insulin sensitivity occurs in peripheral tissue, meaning both adipocytes and myocytes. However, metformin works by increasing sensitivity in muscle tissue only.
Unlike sulfonylureas, it doesn't cause an increase in fat. In terms of dropping body fat and maintaining insulin sensitivity while using insulin, this is the superior drug. Dosages range between 500-2500 mg per day with meals. They typically come in 500 and 850 mg tabs.
Insulin
In terms of staying absolutely insulin sensitive, avoiding exogenous insulin is important. However, for those of you who choose to use insulin in order to increase muscle mass, it's important to use metformin along with it and even afterward. Be careful though. Every time you inject a fast acting insulin, you run the risk of going into a hypoglycemic shock and dying, which would really mess up your sex life. You can come up with your own ideas on how to avoid this, or you can do what my large friend (6'3", 285 lbs at 8% body fat) does: sit down with a container of dextrose or maltose and drink it until you no longer feel like passing out. Needless to say, this is scary stuff!
In terms of reducing insulin resistance, one type of insulin actually does the job. It's called insulin lispro. It's made with recombinant DNA technology by altering the pharmaceutical profile. This insulin is also known as Humalog, and it's the only form of insulin to which patients with severe insulin resistance responded.
It has a shorter and more consistent duration of action than most other types of insulin, which makes it safer and less likely to increase body fat. As a side note, if you're using any type of insulin, make sure to supplement with magnesium and potassium, as they're both depleted while using it.
Anabolic steroids
While anabolic steroids have many affects on the human body, one of interest to us may be their ability to increase glucose disposal, possibly leading to an increase in insulin sensitivity. In one study, healthy males were given 300 mg/week of either Testosterone enanthate or nandrolone decanoate for six weeks. At the end of the study, it was found that while TE had no detrimental effect on glucose disposal, ND had increased glucose disposal to a significant degree.(54) These findings were in conflict with what was found in the use of 17-alpha alkylated steroids. So, according to this, the best anabolic to use while trying to improve insulin sensitivity may be Deca! The benefits of this 'roid never seem to end.
Conclusion
Hopefully I've convinced you of the importance of what types of macronutrients you consume, as well as what supplements and drugs you use. They can all have dramatic affects on your ability to gain muscle and lose body fat through their affects on insulin. Again, a combination of omega-3, omega-6, and some monounsaturated fat would be the best bet — not only for insulin sensitivity, but for hormonal benefits as well.
For instance, if you just have to eat that rice cake, or cracker, or piece of Wonder Bread, slather some natural peanut butter on it (the kind where the oil is visible on top), or take a swig of Flax seed oil beforehand. That'll slow the absorption considerably, which will diminish the insulin response.
Give the supplements that I listed a try and see if you like them. I don't think it's necessary to use all of them concurrently, but you might want to experiment with a few — like maybe vanadyl sulfate and alpha lipoic acid — and see how they work before trying the others. Lastly, if you're going to use drugs, try to use Humalog, Deca, and definitely give metformin a try.
Remember, when it comes to insulin, you either have to tame the beast and make it work for you or risk getting controlled by it. I'll choose the former!
References:
1. Roberts SB. "High-glycemic index foods, hunger, and obesity: is there a connection?" Nutr Rev. 2000 Jan;58(6):163-9
2. Lin S, et al. "A prospective study of dietary glycemic load, carbohydrate intake, and risk of coronary heart disease in U.S. women." Am J Clin Nutr 2000 Jun; 71(6):1455-61
3. Ludwig DS, et al. "High glycemic index foods, overeating, and obesity." Pediatrics 1999 Mar;103(3):E26
4. Goodfriend TL, et al. "Plasma aldosterone, plasma lipoproteins, obesity and insulin resistance in humans." Prostaglandins Leukot Essent Fatty Acids 1999 May-Jun;60(5-6):401-5
5. Lee ZS, et al. "Plasma insulin, growth hormone, cortisol, and central obesity among young Chinese type 2 diabetic pateints." Diabetes Care 1999 Sep;22(9):1450-7
6. Striffler JS, et al. "Overproduction of insulin in the chromium deficient rat." Metabolism 1999 Aug;48(8):1063-8
7. Bar-On H, et al. "Plasma total homocysteine levels in subjects with hyperinsulinemia." J Intern Med. 2000 Feb;247(2):287-94
8. Slagado LR, et al. "Effect of glycemic control on growth hormone and IGF-1 secretion in patients with type I diabetes mellitus." J Endocrinol Invest 1996 Jul-Aug;19(7):433-
9. Fernandez-Real JM, et al. "Plasma total and glycosylated corticosteroid binding globulin levels are associated with insulin secretion." J Clin Endocrinol Metab 1999 Sep;84(9) 3192-6
10. Hjalmarsen A, Aasebo V, Aakvaag A, Jorde R. "Sex hormone responses in healthy men and male patients with chronic obstructive pulmonary disease during an oral glucose load." Scnd. J. Clin. Lab. Invest. 1996 Nov; 56(7): 635-40
11.Bjorck I, et al. Be J Nutr 2000 Mar; 83 Suppl. 1:S 149-55
12.Christensen L, Hagen C, Henriksen JE, Hang E. "Elevated levels of sex hormone binding globulin in male patients with insulin dependent daibetes mellitus. Effect of improved blood glucose regulation." Dan Med Bull 1997 Nov; 44 (5):547-50
13.Thomas DE, et al. "Carbohydrate feeding before exercise: effect of glycemic index." Int J Sports Med 1991 Apr;12(2):180-6
14.Jarvi AE, et al. "Improved glycemic control and lipid profile and normalized fibrimolytic activity on a low glycemic index diet in type 2 diabetes." Diabetes Care 1999 Jun; 22(1):10-8
15.Wolever TM. "Dietary carbohydrates and insulin action in humans." British J Nutr 2000 Mar;83 Suppl 1:S97-102
16.Anjali Sharma, et al. "Effect of glycemic control and vitamin E supplementation on total glutathione content in non-insulin dependent diabetes mellitus." Ann Nutr Metab 2000;44:11-13
17.Mann JI. "Can dietary intervention produce long-term reduction in insulin resistance?" British J Nutr 2000 Mar; 83 Suppl 1:S169-72
18.Budohoski L, et al. "Effects of saturated and polyunsaturated fat enriched diet on the skeletal muscle insulin sensitivity in young rats." J Physiol Pharmacol 1993 Dec;44(4):391-8
19.Sarkkinen E, et al. "The effects of monounsaturated-fat enriched diet and polyunsaturated fat enriched diet on lipid and glucose metabolism in subjects with impaired glucose tolerance." Eur J Clin Nutr 1996 Sep;50(9):592-8
20.Salas J, et al. "The diet rich in monounsaturated fat modifies in a beneficial way carbohydrate metabolism and arterial pressure." Med Clin (Barc) 1999 Dec 11; 113(20):765-9
21.Storlien LH. "Fish oil prevents insulin resistance induced by high-fat feeding in rats." Science 1987 Aug 21;237(4817):885-8
22.Liu S, et al. "Dietary Omega-3 and polyunsaturated fatty acids modify acyl composition and insulin binding in skeletal muscle sacrolemma." Biochem J 1994 May 1;299(Pt3):831-7
23.Mori Y, et al. "Effect of a highly purified eicosapentaenoic acid ethyl ester on insulin resistance and hypertension in Dahl salt sensitive rats." Metabolism 1999 Sep; 48(9):1089-95
24.Sohal PS, et al. "Dietary Omega 3 fatty acid alters prostaglandin synthesis, glucose transport, and protein turnover in skeletal muscle of healthy and diabetic rats." Biochem J 1992 Sep 1;286 (Pt2):405-11
25.Claudinin MT, et al. "Dietary lipids influence insulin action." Ann NY Acad Sci 1993 Jun 14;683:151-63 Review
26.Koivisto VA, Yki-Jarvinen H. "Fructose and insulin sensitivity in patients with type 2 diabetes." J Intern Med 1993 Feb;233(2):145-53
27.Zhao S, Li X, Wang Z. "Plasma levels of lipids, lipoproteins and apolipoproteins affected by endogenous testosterone." Hunan I Ko Ta Hseuh Pao 1998; 23(3):299-
28.Stellato RK, et al. "Testosterone, sex hormone-binding globulin and the development of type 2 diabetes in middle aged men: prospective results from the Massachusetts male aging study." Diabetes Care 2000 Apr;23(4):490-4
29.Kawasaki H, et al. "vascular effects of insulin." Nippon Yakurigaku Zasshi 2000 May; 115(5):287-94
30.Liljeberg H, Bjorck I. "Effect of a low glycemic index spaghetti meal on glucose tolerance and lipaemia at a subsequent meal in healthy subjects." Eur J. Clin Nutr 2000 Jan;54(1):24-8
31.Furukawa Y. "Enhancement of glucose-induced insulin secretion and modification of glucose metabolism by biotin." Nippon Rinsho 1999 Oct; 57(10):226-9
32.Borboni P, Magnaterra R, Rabini RA, Staffolani R, Porzio O, Sesti G, Fusco A, Mazzanti L, Lauro R, Marlier LN. "Effect of biotin on glucokinase activity, mRNA expression and insulin release in cultured beta-cells." Acta Diabetol 1996 Jul;33(2):154-8
33.G. Paolisso et al., "Chronic Intake of Pharmacological Doses of Vitamin E Might be Useful in the Therapy of Elderly Patients with Coronary Heart Disease." Am. J Clin Nutr 61(1995):848-52
34.Rosolova H, Mayer O Jr., Reaven GM. "Insulin-mediated glucose disposal is decreased in normal subjects with relatively low plasma magnesium concentrations." Metabolism 2000 Mar;49(3):418-20
35.Barbagallo M, Dominguez LJ, Tagliamonte MR, Resnick LM, Paolisso G. "Effects of vitamin E and glutathione on glucose metabolism: role of magnesium." Hypertension 1999 Oct;34(4pt2):1002-6
36.Matsuda M, Mandarino L, DeFronzo RA. "Synergistic interaction of magnesium on glucose metabolism in diabetic rats." Metabolism 1999 Jun;48(6):725-31
37.G. Norbiato, M. Bevilacqua, R. Merino, et al., "Effects of Potassium Supplementation on Insulin Binding and Insulin Action in Human Obesity: protein-Modified Fast and Refeeding." Europ J Clin Invest 44(1984): 414-19
38.K.T. Khaw and J.T. Barrett-Connor. "Dietary Potassium and Blood Pressure in a Population." Am J Clin Nutr 39(1984):963-68
39.S.M. Hegazi et al., "Effect of Zinc Supplementation on Serum Glucose, Insulin, Glucagon, Glucose-6-Phosphatase, and Mineral Levels in Diabetics." J Clin Biochem Nutr 12 (1992):209-15
40.Jacob S, Rnus P, Hermann R, Tritschler HJ, Maerker E, Renn W, Augustin HJ, Dietze GJ, Rett K. "Oral administration of RAE-ALA modulates insulin sensitivity in patients with type 2 diabetes mellitus: a placebo controlled pilot trial." Free Radic Biol Med 1999 Aug; 27(3-4):309-
41.Jacob S, Henriksen EJ, Schiemann AL, Simon I, Clancy DE, Tritschler HJ, Jung WI, Augustin HJ, Dietze GJ. "Enhancement of glucose disposal in patients with type 2 diabetes by ALA." Arzneimittel forschung 1995 Aug;45(8):872-4
42.NaKaya Y, Minami A, Harada N, Sakamoto S, Niwa Y, Ohnaka M. "Taurine improves insulin sensitivity in the Otsuka Long-Evans Tokushima fatty rat, a model of spontaneous type 2 diabetes. Am J Clin Nutr 2000 Jan; 71(1):54-8
43.Goldfine AB, Patti ME, Zuberi L, Goldstein BJ, LeBlanc R, Landaker EJ, Jiang ZY, Willsky GR, Kahn CR. "Metabolic effects of vanadyl sulfate in humans with non insulin dependent diabetes mellitus: in vivo and vitro studies." Metabolsim 2000 Mar; 49(3):400-10
44.Ahmad F, Khalid P, Khan MM, Rastogi AK, Kidwai JR. "Insulin like activity in epicatechin." Acta Diabetol Lat 1989 Oct; Dec;26(4):291-300
45.Manickam M, Ramanathan M, Jahromi Ma, Chansouria JP, Ray AB. "Antihyperglycemic activity of phenolics from Pterocarpus Marsupium." J Nat Prod 1997 Jun;60(6):609-10
46.Jahrom MA, Ray AB. "Antihyperglycemic effect of flavonoids from Pterocarpus Marsupium." J Nat Prod 1993 Jul;56(7):989-94
47.Hii CS, Howell SL. "Effect of flavonoids on insulin secretion and 45C2+ handling in rat islets of Langerhans." J Endocrinol. 1985 Oct;107(1):1-8
48.Shishena A, Shechter Y. "Quercetin selectively inhibits insulin receptor function in vitro and the bio responses of insulin and insulinomimetic agents in rat adipocytes." Biochemistry 1992 Sep;31(34):8059-63
49.J. Welihinda, G. Arvidson, E. Gylfe, et al., "The Insulin-releasing activity of the tropical plant Momordica Charantia." Acta Biol Med Germ 41(1982):1229-40
50.Ahmad N, Hassan MR, Halder H, Bennoor KS. "Effect of Momordica Charantia(Karolla) extracts on fasting and postprandial serum glucose levels in NIDDM patients." Bangladesh Med Res Counc Bull 1999 Apr;25(1):11-3
51.Sarkar S, Pranava M, Marita R. "Demonstration of the hypoglycemic action of Momordica Charantia in a validated animal model of diabetes." Pharmacol Res 1996 Jan;33(1):1-4
52.Ali L, Khan AK, Mamum MI, Mosihuzzaman M, Nahar N, Nur-e-Alam M, Rokeya B. "Studies on hypoglycemic effects of fruit pulp, seed, and whole plant of Momordica Charantia on normal and diabetic model rats." Planta Med 1993 Oct;59(5):408-12
53.Day C, Cartwright T, Provost J, Bailey CJ. "Hypoglycemic effect of Momordica Charantia extracts." Planta Med 1990 Oct; 56(5):426-9
54.Hobbs CJ, et al. "Nandrolone, a 19-nortestosterone, enhances insulin-independent glucose uptake in normal men." J Clin Endocrinol Metab 1996 Apr;81(4):1582-5
