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- 15 aug 2006
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Waarschijnlijk oud nieuws voor een aantal van jullie; maar ik vond het toch nodig om ook eens de nadelen en risico's van bepaalde middelen hier op DBB inzichtelijk te krijgen. Zo kan de evt. toekomstige gebruiker wellicht een betere/verstandigere keuze maken!
--
By Cy Willson.....
IGF-1: Worst Bodybuilding Drug Ever?
Q: What ever happened to IGF-1? It was talked about in 'roid books in the early '90s but you don't hear much about it now, except for a few sleazy supplement companies who are using the name.
A: IGF-1 can allow for hypertrophy of muscle. Will it do such a thing when administered to humans? Yes. However, the gains seen really aren’t spectacular. More often than not, they don’t even come close to gains seen using androgens.
For the most part, people should realize that IGF-1 is primarily responsible for GH’s anabolic effects in skeletal muscle as well as cell proliferation, leading to enlarged internal organs and increasing the risk for cancer dramatically. Oh, and this most certainly includes Long R3 IGF-I as I know some people will try to argue that it's much safer.
Well, in order to give you the total picture, I’m going to go over some basic molecular biology as well as list the direct evidence we have concerning the side effects of IGF-1 and yes, that includes Long R3 IGF-I.
First, people should understand that in the human cell cycle, growth requires growth factors in general. Seems simple enough. The next thing people need to understand is that for a normal cell, death is something that'll inevitably occur via loss of telomerase or apoptosis (programmed cell death). Again, I can’t overemphasize enough that the default pathway in humans is death, not growth. (Reassuring, isn't it?)
Now, when you hear of cancer, malignant cancer, people tend to think of uncontrolled cell division. Essentially though, these transformed cancerous cells are immortalized. Now, many changes are required for this to occur (i.e. increased telomerase, increased bcl-2, increased myc and decreased p53). In the development of cancer, we tend to think of carcingogens consisting of both initiators and promoters. For instance, some initiators are UV radiation and tobacco smoke, usually causing DNA damage or mutation, whereas promoters tend to stimulate cell division. A few examples are phorbol esters, hormones (e.g. estrogens) and yes, growth factors.
Now, keep in mind both events, initiation and promotion, are required for the development of malignant cells. As a side note, viral infection can also lead to the two events, but I digress. Anyhow, normally a cell serves its purpose and then dies via apoptosis. However, malignant cells don’t undergo apoptosis. They are, as I said before, immortal. The normal triggers to apoptosis are DNA damage, loss of cell-matrix contact, loss of cell to cell contact, and last but most certainly not least, lack of growth factors.
When you introduce growth factors, you’re providing the catalyst for cancer formation, so to speak. Let’s say, for instance, you get many sunburns during your lifetime. Now, let’s say that one cell has its DNA damaged or altered. This, in and of itself, isn’t too much of a concern as this is only one part of the equation, the iniation. The second part is the promoter (including growth factors).
Well, let’s imagine we introduce growth factors to the cell which has damaged or mutated DNA and it then begins to divide at a more and more rapid rate until it won’t stop. Voila, you have a tumor, which is now capable of even faster growth as well as being invasive (able to invade surrounding tissues) and metastatic (able to cause growth in completely unrelated and distant tissues) in regard to other tissues.
In other words, you now have a malignant tumor, which we commonly refer to as cancer. The fact is, cancer stems from just one cell, just one cell, which begins to divide uncontrollably. People often talk about GH and the side effects thereof, but what most don’t realize is that many of those side effects aren't necessarily mediated by growth hormone but by IGF-1.
Many people may go their whole lives with some DNA damage (or mutation rather) and never have cancer, but with the addition of growth factors, you’re asking for trouble. Even more specifically, you can increase the risk of developing rare forms of cancer, like sarcomas, which are tumors commonly found in connective tissues (i.e. muscle, bone, cartilage, etc.)
Okay, now on to the more cosmetic side effects. With Long R3 IGF-I, it was shown to stimulate growth of the gastrointestinal tract. IGF-1 actually had no effect on body weight and wet tissue weight of the small and large intestine, whereas Long R3 IGF-I resulted in a 20% increase in the weight of the small and large intestine. This is what's causing a "GH gut" although using Long R3 IGF-I is much, much worse than using GH.
Something else to keep in mind is that Long R3 IGF-I was shown to be even more potent than IGF-1 in inhibiting apoptosis and thus its potential for causing cancer is many times greater.
Another idea is that IGF-1 may also keep telomerase activity high, which as we noted previously is a contributing factor for the loss of regulation in terms of cell division. In other words, it again can substantially increase the risk for developing cancer. Long R3 IGF-I was shown to increase telomerase activity in human prostate cancer cells, whereas IGF-1 had no effect.
So, when I tell you to stay away from IGF-1, I’m actually referring to Long R3 IGF-I as it’s what's most commonly circulated and used. Although both aren't something a person should use, Long R3 IGF-1 is probably the worst choice you can make.
So, unless you’re an IFBB pro who consistently places in the top ten at popular contests, you should forget about using IGF-1, or specifically the analogue of IGF-1 called Long R3 IGF-I. It’s really not worth the risk. This, out of all the compounds that bodybuilders may use, is probably the worst in terms of potential side effects.
If you want a true distended belly and increased risk of cancer, be my guest. (47-52)
References Cited
1. Tuzcu A, et al. "Insulin sensitivity and hyperprolactinemia." J Endocrinol Invest. 2003 Apr;26(4):341-6
2. Freemark M, et al. "Body weight and fat deposition in prolactin receptor-deficient mice." Endocrinology. 2001 Feb;142(2):532-7
3. Wasada T, Kawahara R, Iwamoto Y. "Lack of evidence for bromocriptine effect on glucose tolerance, insulin resistance, and body fat stores in obese type 2 diabetic patients." Diabetes Care. 2000 Jul;23(7):1039-40
4. Pijl H, et al. "Bromocriptine: a novel approach to the treatment of type 2 diabetes." Diabetes Care. 2000 Aug;23(8):1154-61
5. Ohem N, Holzl J. Some new investigations on Ilex paraguariensis - Flavonoids and triterpenes. Planta Med 1988; 54: 576
6. Bisset NG, ed. Herbal Drugs and Phytopharmaceuticals (Wichtl M, ed., German edition). Stuttgart: Medpharm, 1994
7. Duke JA. Handbook of Medicinal Herbs. Boca Raton: CRC, 1985
8. Martindale: The Extra Pharmacopoeia, 29th edn. (Reynolds JEF, ed.). London: The Pharmaceutical Press, 1989
9. The Merck Index. An Encyclopedia of Chemicals, Drugs and Biologicals, 11th edn. Rahway, NJ: Merck, 1989
10. Carani C, et al. "Role of oestrogen in male coïtusual behaviour: insights from the natural model of aromatase deficiency." Clin Endocrinol (Oxf). 1999 Oct;51(4):517-24
11. Scordalakes EM, Imwalle DB, Rissman EF. "Oestrogen's masculine side: mediation of mating in male mice." Reproduction. 2002 Sep;124(3):331-8
12. Brady BM, et al. "Demonstration of progesterone receptor-mediated gonadotrophin suppression in the human male." Clin Endocrinol (Oxf) 2003 Apr;58(4):506-12
13. Bauer ER, et al. "Characterisation of the affinity of different anabolics and synthetic hormones to the human androgen receptor, human coïtus hormone binding globulin and to the bovine progestin receptor." APMIS. 2000 Dec;108(12):838-46
14. Markiewicz L, Gurpide E. "Estrogenic and progestagenic activities of physiologic and synthetic androgens, as measured by in vitro bioassays. Methods Find Exp Clin Pharmacol. 1997 May;19(4):215-22
15. Breithaupt-Grogler K, Niebch G, Schneider E et al: Dose-proportionality of oral thioctic acid - coincidence of assessments via pooled plasma and individual data. Eur J Pharm Sci 1999; 8(1):57-65
16. Hermann R, Niebch G, Borbe HO et al: Enantioselective pharmacokinetics and bioavailability of different racemic alpha-lipoic acid formulations in healthy volunteers. Eur J Pharm Sci 1996; 4:167-174
17. Gleiter CH, Schug BS, Hermann R et al: Influence of food intake on the bioavailability of thioctic acid enantiomers. Eur J Clin Pharmacol 1996; 50(6):513-514
18. Fachinformation: Pleomix-Alpha(R), alpha-Liponsaeure. Illa Health Care GmbH, Geretsried, 1996
19. Streeper RS, Henriksen EJ, Jacob S et al: Differential effects of lipoic acid steroisomers on glucose metabolism in insulin-resistant skeletal muscle. Am J Physiol 1997; 273(1 pt 1):E185-E191
20. Khamaisi M, Potashnik R, Tirosh A et al: Lipoic acid reduces glycemia and increases muscle GLUT4 content in streptozotocin-diabetic rats. Metabolism 1997; 46(7):763-768
21. Henriksen EJ, Jacob S, Streeper RS et al: Stimulated by alpha-lipoic acid of glucose transport activity in skeletal muscle of lean and obese Zucker rats. Life Sci 1997; 61(8):805-812
22. Wickramasinghe SN & Hasan R: In vitro effects of vitamin C, thioctic acid and dihydrolipoic acid on the cytotoxicity of post-ethanol serum. Biochem Pharmacol 1992; 43(3):407-411
23. Dimpfel W, Spueler M, Pierau F-K et al: Thioctic acid induces dose-dependent sprouting of neurites in cultured rat neuroblastoma cells. Dev Pharmacol Ther 1990; 14(3):193-199
24. Prehn JHM, Karkoutly C, Nuglisch J et al: Dihyrolipoate reduces neuronal injury after cerebral ischemia. J Cereb Blood Flow Metab 1992; 12(1):78-87
25. Burkart V, Koike T, Brenner HH et al: Dihydrolipoic acid protects pancreatic islet cells from inflammatory attack. Agents Actions 1993; 38(1-2):60-65
26. Bauer A, Harrer T, Peukert M et al: Alpha-lipoic acid is an effective inhibitor of human immuno-deficiency Virus (HIV-1) replication. Klin Wochenschr 1991; 69(15):722-724
27. Suzuki YJ, Aggarwal BB & Packer L: alpha-Lipoic acid is a potent inhibitor of NF-kappaB activation in human T cells. Biochem Biophys Res Commun 1992; 189(3):1709-1715
28. Bierhaus A, Chevion S, Chevion M et al: Advanced glycation end product-induced activation of NF-kappaB is suppressed by alpha-lipoic acid in cultured endothelial cells. Diabetes 1997; 46(9):1481-1490
29. Constantinescu A, Tritschler H & Packer L: alpha-Lipoic acid protects against hemolysis of human erythrocytes induced by peroxyl radicals. Biochem Mol Biol Int 1994; 33(4):669-679
30. Greene EL, Nelson BA, Robinson KA, Buse MG. "alpha-Lipoic acid prevents the development of glucose-induced insulin resistance in 3T3-L1 adipocytes and accelerates the decline in immunoreactive insulin during cell incubation." Metabolism 2001 Sep;50(9):1063-9
31. Maddux BA, et al. "Protection against oxidative stress-induced insulin resistance in rat L6 muscle cells by mircomolar concentrations of alpha-lipoic acid." Diabetes 2001 Feb;50(2):404-10
32. Weinstein RB, Tritschler HJ, Henriksen EJ. "Antioxidant alpha-lipoic acid and protein turnover in insulin-resistant rat muscle." Free Radic Biol Med 2001 Feb 15;30(4):383-8
33. Yaworsky K, Somwar R, Ramlal T, Tritschler HJ, Klip A. "Engagement of the insulin-sensitive pathway in the stimulation of glucose transport by alpha-lipoic acid in 3T3-L1 adipocytes." Diabetologia 2000 Mar;43(3):294-303
34. Jacob S, et al. "Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled pilot trial." Free Radic Biol Med 1999 Aug;27(3-4):309-14
35. Estrada DE, et al. "Stimulation of glucose uptake by the natural coenzyme alpha-lipoic acid/thioctic acid: participation of elements of the insulin signaling pathway." Diabetes 1996 Dec;45(12):1798-804
36. Hundal RS, et al. "Mechanism by which metformin reduces glucose production in type 2 diabetes." Diabetes 2000 Dec;49(12):2063-9
37. Anderwald C, et al. "Inhibition of glucose production and stimulation of bile flow by R (+)-alpha-lipoic acid enantiomer in rat liver." Liver 2002 Aug;22(4):355-62
38. Saengsirisuwan V, Perez FR, Kinnick TR, Henriksen EJ. "Effects of exercise training and antioxidant R-ALA on glucose transport in insulin-sensitive rat skeletal muscle." J Appl Physiol 2002 Jan;92(1):50-8
39. Evans JL, Goldfine ID. "Alpha-lipoic acid: a multifunctional antioxidant that improves insulin sensitivity in patients with type 2 diabetes." Diabetes Technol Ther 2000 Autumn;2(3):401-13
40. Saengsirisuwan V, Kinnick TR, Schmit MB, Henriksen EJ. "Interactions of exercise training and lipoic acid on skeletal muscle glucose transport in obese Zucker rats." J Appl Physiol 2001 Jul;91(1):145-53
41. Konrad T. "alpha-Lipoic acid treatment decreases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with type 2 diabetes." Diabetes Care 1999 Feb;22(2):280-7
42. Jacob S, et al. "Enhancement of glucose disposal in patients with type 2 diabetes by alpha-lipoic acid." Arzneimittelforschung 1995 Aug;45(8):872-4
43. Jacob S, Rett K, Henriksen EJ, Haring HU. "Thioctic acid—effects on insulin sensitivity and glucose-metabolism." Biofactors 1999;10(2-3):169-74
44. Jacob S, Henriksen EJ, Tritschler HJ, Augustin HJ, Dietze GJ. "Improvement of insulin-stimulated glucose-disposal in type 2 diabetes after repeated parenteral administration of thioctic acid." Exp Clin Endocrinol Diabetes 1996;104(3):284-8
45. Bigsby RM, Caperell-Grant A, Madhukar BV. "Xenobiotics released from fat during fasting produce estrogenic effects in ovariectomized mice." Cancer Res. 1997 Mar 1;57(5):865-9
46. McCurdy CE, Davidson RT, Cartee GD. "Brief calorie restriction increases Akt2 phosphorylation in insulin-stimulated rat skeletal muscle." Am J Physiol Endocrinol Metab. 2003 Oct;285(4):E693-E700.
47. Steeb CB, Trahair JF, Read LC. "Administration of insulin-like growth factor-I (IGF-I) peptides for three days stimulates proliferation of the small intestinal epithelium in rats." Gut. 1995 Nov;37(5):630-8
48. Wetterau LA, Francis MJ, Ma L, Cohen P. "Insulin-like growth factor I stimulates telomerase activity in prostate cancer cells." J Clin Endocrinol Metab. 2003 Jul;88(7):3354-9
49. Devi GR, Graham DL, Oh Y, Rosenfeld RG. "Effect of IGFBP-3 on IGF- and IGF-analogue-induced insulin-like growth factor-I receptor (IGFIR) signalling." Growth Horm IGF Res. 2001 Aug;11(4):231-9
50. Nickerson T, Huynh H, Pollak M. "Insulin-like growth factor binding protein-3 induces apoptosis in MCF7 breast cancer cells." Biochem Biophys Res Commun. 1997 Aug 28;237(3):690-3
51. Vink-van Wijngaarden T, Pols HA, Buurman CJ, Birkenhager JC, van Leeuwen JP. "Inhibition of insulin- and insulin-like growth factor-I-stimulated growth of human breast cancer cells by 1,25-dihydroxyvitamin D3 and the vitamin D3 analogue EB1089." Eur J Cancer. 1996 May;32A(5):842-8
52. Wetterau LA, Francis MJ, Ma L, Cohen P. "Insulin-like growth factor I stimulates telomerase activity in prostate cancer cells." J Clin Endocrinol Metab. 2003 Jul;88(7):3354-9
--
By Cy Willson.....
IGF-1: Worst Bodybuilding Drug Ever?
Q: What ever happened to IGF-1? It was talked about in 'roid books in the early '90s but you don't hear much about it now, except for a few sleazy supplement companies who are using the name.
A: IGF-1 can allow for hypertrophy of muscle. Will it do such a thing when administered to humans? Yes. However, the gains seen really aren’t spectacular. More often than not, they don’t even come close to gains seen using androgens.
For the most part, people should realize that IGF-1 is primarily responsible for GH’s anabolic effects in skeletal muscle as well as cell proliferation, leading to enlarged internal organs and increasing the risk for cancer dramatically. Oh, and this most certainly includes Long R3 IGF-I as I know some people will try to argue that it's much safer.
Well, in order to give you the total picture, I’m going to go over some basic molecular biology as well as list the direct evidence we have concerning the side effects of IGF-1 and yes, that includes Long R3 IGF-I.
First, people should understand that in the human cell cycle, growth requires growth factors in general. Seems simple enough. The next thing people need to understand is that for a normal cell, death is something that'll inevitably occur via loss of telomerase or apoptosis (programmed cell death). Again, I can’t overemphasize enough that the default pathway in humans is death, not growth. (Reassuring, isn't it?)
Now, when you hear of cancer, malignant cancer, people tend to think of uncontrolled cell division. Essentially though, these transformed cancerous cells are immortalized. Now, many changes are required for this to occur (i.e. increased telomerase, increased bcl-2, increased myc and decreased p53). In the development of cancer, we tend to think of carcingogens consisting of both initiators and promoters. For instance, some initiators are UV radiation and tobacco smoke, usually causing DNA damage or mutation, whereas promoters tend to stimulate cell division. A few examples are phorbol esters, hormones (e.g. estrogens) and yes, growth factors.
Now, keep in mind both events, initiation and promotion, are required for the development of malignant cells. As a side note, viral infection can also lead to the two events, but I digress. Anyhow, normally a cell serves its purpose and then dies via apoptosis. However, malignant cells don’t undergo apoptosis. They are, as I said before, immortal. The normal triggers to apoptosis are DNA damage, loss of cell-matrix contact, loss of cell to cell contact, and last but most certainly not least, lack of growth factors.
When you introduce growth factors, you’re providing the catalyst for cancer formation, so to speak. Let’s say, for instance, you get many sunburns during your lifetime. Now, let’s say that one cell has its DNA damaged or altered. This, in and of itself, isn’t too much of a concern as this is only one part of the equation, the iniation. The second part is the promoter (including growth factors).
Well, let’s imagine we introduce growth factors to the cell which has damaged or mutated DNA and it then begins to divide at a more and more rapid rate until it won’t stop. Voila, you have a tumor, which is now capable of even faster growth as well as being invasive (able to invade surrounding tissues) and metastatic (able to cause growth in completely unrelated and distant tissues) in regard to other tissues.
In other words, you now have a malignant tumor, which we commonly refer to as cancer. The fact is, cancer stems from just one cell, just one cell, which begins to divide uncontrollably. People often talk about GH and the side effects thereof, but what most don’t realize is that many of those side effects aren't necessarily mediated by growth hormone but by IGF-1.
Many people may go their whole lives with some DNA damage (or mutation rather) and never have cancer, but with the addition of growth factors, you’re asking for trouble. Even more specifically, you can increase the risk of developing rare forms of cancer, like sarcomas, which are tumors commonly found in connective tissues (i.e. muscle, bone, cartilage, etc.)
Okay, now on to the more cosmetic side effects. With Long R3 IGF-I, it was shown to stimulate growth of the gastrointestinal tract. IGF-1 actually had no effect on body weight and wet tissue weight of the small and large intestine, whereas Long R3 IGF-I resulted in a 20% increase in the weight of the small and large intestine. This is what's causing a "GH gut" although using Long R3 IGF-I is much, much worse than using GH.
Something else to keep in mind is that Long R3 IGF-I was shown to be even more potent than IGF-1 in inhibiting apoptosis and thus its potential for causing cancer is many times greater.
Another idea is that IGF-1 may also keep telomerase activity high, which as we noted previously is a contributing factor for the loss of regulation in terms of cell division. In other words, it again can substantially increase the risk for developing cancer. Long R3 IGF-I was shown to increase telomerase activity in human prostate cancer cells, whereas IGF-1 had no effect.
So, when I tell you to stay away from IGF-1, I’m actually referring to Long R3 IGF-I as it’s what's most commonly circulated and used. Although both aren't something a person should use, Long R3 IGF-1 is probably the worst choice you can make.
So, unless you’re an IFBB pro who consistently places in the top ten at popular contests, you should forget about using IGF-1, or specifically the analogue of IGF-1 called Long R3 IGF-I. It’s really not worth the risk. This, out of all the compounds that bodybuilders may use, is probably the worst in terms of potential side effects.
If you want a true distended belly and increased risk of cancer, be my guest. (47-52)
References Cited
1. Tuzcu A, et al. "Insulin sensitivity and hyperprolactinemia." J Endocrinol Invest. 2003 Apr;26(4):341-6
2. Freemark M, et al. "Body weight and fat deposition in prolactin receptor-deficient mice." Endocrinology. 2001 Feb;142(2):532-7
3. Wasada T, Kawahara R, Iwamoto Y. "Lack of evidence for bromocriptine effect on glucose tolerance, insulin resistance, and body fat stores in obese type 2 diabetic patients." Diabetes Care. 2000 Jul;23(7):1039-40
4. Pijl H, et al. "Bromocriptine: a novel approach to the treatment of type 2 diabetes." Diabetes Care. 2000 Aug;23(8):1154-61
5. Ohem N, Holzl J. Some new investigations on Ilex paraguariensis - Flavonoids and triterpenes. Planta Med 1988; 54: 576
6. Bisset NG, ed. Herbal Drugs and Phytopharmaceuticals (Wichtl M, ed., German edition). Stuttgart: Medpharm, 1994
7. Duke JA. Handbook of Medicinal Herbs. Boca Raton: CRC, 1985
8. Martindale: The Extra Pharmacopoeia, 29th edn. (Reynolds JEF, ed.). London: The Pharmaceutical Press, 1989
9. The Merck Index. An Encyclopedia of Chemicals, Drugs and Biologicals, 11th edn. Rahway, NJ: Merck, 1989
10. Carani C, et al. "Role of oestrogen in male coïtusual behaviour: insights from the natural model of aromatase deficiency." Clin Endocrinol (Oxf). 1999 Oct;51(4):517-24
11. Scordalakes EM, Imwalle DB, Rissman EF. "Oestrogen's masculine side: mediation of mating in male mice." Reproduction. 2002 Sep;124(3):331-8
12. Brady BM, et al. "Demonstration of progesterone receptor-mediated gonadotrophin suppression in the human male." Clin Endocrinol (Oxf) 2003 Apr;58(4):506-12
13. Bauer ER, et al. "Characterisation of the affinity of different anabolics and synthetic hormones to the human androgen receptor, human coïtus hormone binding globulin and to the bovine progestin receptor." APMIS. 2000 Dec;108(12):838-46
14. Markiewicz L, Gurpide E. "Estrogenic and progestagenic activities of physiologic and synthetic androgens, as measured by in vitro bioassays. Methods Find Exp Clin Pharmacol. 1997 May;19(4):215-22
15. Breithaupt-Grogler K, Niebch G, Schneider E et al: Dose-proportionality of oral thioctic acid - coincidence of assessments via pooled plasma and individual data. Eur J Pharm Sci 1999; 8(1):57-65
16. Hermann R, Niebch G, Borbe HO et al: Enantioselective pharmacokinetics and bioavailability of different racemic alpha-lipoic acid formulations in healthy volunteers. Eur J Pharm Sci 1996; 4:167-174
17. Gleiter CH, Schug BS, Hermann R et al: Influence of food intake on the bioavailability of thioctic acid enantiomers. Eur J Clin Pharmacol 1996; 50(6):513-514
18. Fachinformation: Pleomix-Alpha(R), alpha-Liponsaeure. Illa Health Care GmbH, Geretsried, 1996
19. Streeper RS, Henriksen EJ, Jacob S et al: Differential effects of lipoic acid steroisomers on glucose metabolism in insulin-resistant skeletal muscle. Am J Physiol 1997; 273(1 pt 1):E185-E191
20. Khamaisi M, Potashnik R, Tirosh A et al: Lipoic acid reduces glycemia and increases muscle GLUT4 content in streptozotocin-diabetic rats. Metabolism 1997; 46(7):763-768
21. Henriksen EJ, Jacob S, Streeper RS et al: Stimulated by alpha-lipoic acid of glucose transport activity in skeletal muscle of lean and obese Zucker rats. Life Sci 1997; 61(8):805-812
22. Wickramasinghe SN & Hasan R: In vitro effects of vitamin C, thioctic acid and dihydrolipoic acid on the cytotoxicity of post-ethanol serum. Biochem Pharmacol 1992; 43(3):407-411
23. Dimpfel W, Spueler M, Pierau F-K et al: Thioctic acid induces dose-dependent sprouting of neurites in cultured rat neuroblastoma cells. Dev Pharmacol Ther 1990; 14(3):193-199
24. Prehn JHM, Karkoutly C, Nuglisch J et al: Dihyrolipoate reduces neuronal injury after cerebral ischemia. J Cereb Blood Flow Metab 1992; 12(1):78-87
25. Burkart V, Koike T, Brenner HH et al: Dihydrolipoic acid protects pancreatic islet cells from inflammatory attack. Agents Actions 1993; 38(1-2):60-65
26. Bauer A, Harrer T, Peukert M et al: Alpha-lipoic acid is an effective inhibitor of human immuno-deficiency Virus (HIV-1) replication. Klin Wochenschr 1991; 69(15):722-724
27. Suzuki YJ, Aggarwal BB & Packer L: alpha-Lipoic acid is a potent inhibitor of NF-kappaB activation in human T cells. Biochem Biophys Res Commun 1992; 189(3):1709-1715
28. Bierhaus A, Chevion S, Chevion M et al: Advanced glycation end product-induced activation of NF-kappaB is suppressed by alpha-lipoic acid in cultured endothelial cells. Diabetes 1997; 46(9):1481-1490
29. Constantinescu A, Tritschler H & Packer L: alpha-Lipoic acid protects against hemolysis of human erythrocytes induced by peroxyl radicals. Biochem Mol Biol Int 1994; 33(4):669-679
30. Greene EL, Nelson BA, Robinson KA, Buse MG. "alpha-Lipoic acid prevents the development of glucose-induced insulin resistance in 3T3-L1 adipocytes and accelerates the decline in immunoreactive insulin during cell incubation." Metabolism 2001 Sep;50(9):1063-9
31. Maddux BA, et al. "Protection against oxidative stress-induced insulin resistance in rat L6 muscle cells by mircomolar concentrations of alpha-lipoic acid." Diabetes 2001 Feb;50(2):404-10
32. Weinstein RB, Tritschler HJ, Henriksen EJ. "Antioxidant alpha-lipoic acid and protein turnover in insulin-resistant rat muscle." Free Radic Biol Med 2001 Feb 15;30(4):383-8
33. Yaworsky K, Somwar R, Ramlal T, Tritschler HJ, Klip A. "Engagement of the insulin-sensitive pathway in the stimulation of glucose transport by alpha-lipoic acid in 3T3-L1 adipocytes." Diabetologia 2000 Mar;43(3):294-303
34. Jacob S, et al. "Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled pilot trial." Free Radic Biol Med 1999 Aug;27(3-4):309-14
35. Estrada DE, et al. "Stimulation of glucose uptake by the natural coenzyme alpha-lipoic acid/thioctic acid: participation of elements of the insulin signaling pathway." Diabetes 1996 Dec;45(12):1798-804
36. Hundal RS, et al. "Mechanism by which metformin reduces glucose production in type 2 diabetes." Diabetes 2000 Dec;49(12):2063-9
37. Anderwald C, et al. "Inhibition of glucose production and stimulation of bile flow by R (+)-alpha-lipoic acid enantiomer in rat liver." Liver 2002 Aug;22(4):355-62
38. Saengsirisuwan V, Perez FR, Kinnick TR, Henriksen EJ. "Effects of exercise training and antioxidant R-ALA on glucose transport in insulin-sensitive rat skeletal muscle." J Appl Physiol 2002 Jan;92(1):50-8
39. Evans JL, Goldfine ID. "Alpha-lipoic acid: a multifunctional antioxidant that improves insulin sensitivity in patients with type 2 diabetes." Diabetes Technol Ther 2000 Autumn;2(3):401-13
40. Saengsirisuwan V, Kinnick TR, Schmit MB, Henriksen EJ. "Interactions of exercise training and lipoic acid on skeletal muscle glucose transport in obese Zucker rats." J Appl Physiol 2001 Jul;91(1):145-53
41. Konrad T. "alpha-Lipoic acid treatment decreases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with type 2 diabetes." Diabetes Care 1999 Feb;22(2):280-7
42. Jacob S, et al. "Enhancement of glucose disposal in patients with type 2 diabetes by alpha-lipoic acid." Arzneimittelforschung 1995 Aug;45(8):872-4
43. Jacob S, Rett K, Henriksen EJ, Haring HU. "Thioctic acid—effects on insulin sensitivity and glucose-metabolism." Biofactors 1999;10(2-3):169-74
44. Jacob S, Henriksen EJ, Tritschler HJ, Augustin HJ, Dietze GJ. "Improvement of insulin-stimulated glucose-disposal in type 2 diabetes after repeated parenteral administration of thioctic acid." Exp Clin Endocrinol Diabetes 1996;104(3):284-8
45. Bigsby RM, Caperell-Grant A, Madhukar BV. "Xenobiotics released from fat during fasting produce estrogenic effects in ovariectomized mice." Cancer Res. 1997 Mar 1;57(5):865-9
46. McCurdy CE, Davidson RT, Cartee GD. "Brief calorie restriction increases Akt2 phosphorylation in insulin-stimulated rat skeletal muscle." Am J Physiol Endocrinol Metab. 2003 Oct;285(4):E693-E700.
47. Steeb CB, Trahair JF, Read LC. "Administration of insulin-like growth factor-I (IGF-I) peptides for three days stimulates proliferation of the small intestinal epithelium in rats." Gut. 1995 Nov;37(5):630-8
48. Wetterau LA, Francis MJ, Ma L, Cohen P. "Insulin-like growth factor I stimulates telomerase activity in prostate cancer cells." J Clin Endocrinol Metab. 2003 Jul;88(7):3354-9
49. Devi GR, Graham DL, Oh Y, Rosenfeld RG. "Effect of IGFBP-3 on IGF- and IGF-analogue-induced insulin-like growth factor-I receptor (IGFIR) signalling." Growth Horm IGF Res. 2001 Aug;11(4):231-9
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