Improvement of Insulin Resistance by Panax Ginseng in Fructose-rich Chow-fed Rats

Abstract

In an attempt to probe a new target for handling insulin resistance, we used Panax ginseng root to screen the effect on insulin resistance induced by fructose-rich chow in rats. Insulin action on glucose disposal rate was measured using the glucose-insulin index, which is the product of the areas under the curve of glucose and insulin during the intraperitoneal glucose tolerance test. Oral administration of Panax ginseng root (125.0 mg/kg) into rats three times daily for three days after receiving fructose-rich chow for four weeks reversed the increased glucose-insulin index, indicating that Panax ginseng root has the ability to improve insulin sensitivity. In addition, the plasma glucose concentrations in rats repeatedly treated with Panax ginseng root were not elevated as markedly as those of the vehicle-treated group during the fructose-rich chow-feeding period. Also, the time in which the plasma glucose-lowering response to tolbutamide (10.0 mg/kg, i. p.) receded in fructose-rich chow fed rats was markedly delayed by repeated Panax ginseng root treatment compared to the vehicle-treated group. The plasma glucose-lowering activity of tolbutamide is believed to depend on the secretion of endogenous insulin, which is widely used as an indicator of insulin resistance development. Thus, it provided supportive data that oral administration of Panax ginseng root could delay the development of insulin resistance in rats. In conclusion, our results suggest that oral administration of Panax ginseng root improves insulin sensitivity and may be used as an adjuvant therapy for treating diabetic patients with insulin resistance.

Fructose-rich chow - Insulin resistance - Intraperitoneal glucose tolerance test - Panax ginseng - Tolbutamide

References

• 1 Kiefer D, Pantuso T. Panax ginseng.  Am Fam Physician. 2003;  68 1539-1542
• 2 Chen X C, Zhu Y G, Zhu L A, Huang C, Chen Y, Chen L M, Fang F, Zhou Y C, Zhao C H. Ginsenoside Rg1 attenuates dopamine-induced apoptosis in PC12 cells by suppressing oxidative stress.  Eur J Pharmacol. 2003;  473 1-7
• 3 Kennedy D O, Scholey A B. Ginseng: potential for the enhancement of cognitive performance and mood.  Pharmacol Biochem Behav. 2003;  75 687-700
• 4 Block K I, Mead M N. Immune system effects of echinacea, ginseng, and astragalus: a review.  Integrative Cancer Therapies. 2003;  2 247-267
• 5 van Kampen J, Robertson H, Hagg T, Drobitch R. Neuroprotective actions of the ginseng extract G115 in two rodent models of Parkinson’s disease.  Exp Neurol. 2003;  184 521-529
• 6 Lopez-Candales A. Metabolic syndrome X: a comprehensive review of the pathophysiology and recommended therapy.  J Med. 2001;  32 283-300
• 7 Bensky D, Gamble A. Chinese Herbal Medicine Materia Medica. Seattle, WA; Eastland Press 1993
• 8 Huang K C. The Pharmacology of Chinese Herbs. Boca Raton, FL; CRC Press 1999
• 9 Lee F C. Facts About Ginseng, The Elixir of Life. Elizabeth, NJ; Hollyn International Corp 1992
• 10 Attele A S, Wu J A, Yuan C S. Multiple pharmacological effects of ginseng.  Biochem Pharmacol. 1999;  58 1685-1693
• 11 Kimura M, Waki I, Tanaka O, Nagai Y, Shibata S. Pharmacological sequential trials for the fractionation of components with hypoglycemic activity in alloxan diabetic mice from ginseng radix.  J Pharmacobiodyn. 1981;  4 402-409
• 12 Kimura M, Suzuki J. The pattern of action of blended Chinese traditional medicines to glucose tolerance curves in genetically diabetic KK-CA^y mice.  J Pharmacobiodyn. 1981;  4 907-915
• 13 Yokozawa T, Kobayashi T, Oura H, Kawashima Y. Studies on the mechanism of the hypoglycemic activity of ginsenoside-Rb₂ in streptozotocindiabetic rats.  Chem Pharm Bull. 1985;  33 869-872
• 14 Kruszynska Y T, Olefsky J M. Cellular and molecular mechanisms of non-insulin dependent diabetes mellitus.  J Invest Med. 1996;  44 413-428
• 15 Wang L, Higashiura K, Ura N, Miura T, Shimamoto K. Chinese medicine, Jiang-Tang-Ke-Li, improves insulin resistance by modulating muscle fiber composition and muscle tumor necrosis factor-alpha in fructose-fed rats.  Hypertens Res. 2003;  26 527-532
• 16 Su C F, Chang Y Y, Pai H H, Liu I M, Lo C Y, Cheng J T. Infusion of β-endorphin improves insulin resistance in fructose-fed rats.  Horm Metab Res (in press). 2004;  36 571-577
• 17 Peyron-Caso E, Fluteau-Nadler S, Kabir M, Guerre-Millo M, Quignard-Boulange A, Slama G, Rizkalla S W. Regulation of glucose transport and transporter 4 (GLUT-4) in muscle and adipocytes of sucrose-fed rats: effects of N-3 poly- and monounsaturated fatty acids.  Horm Metab Res. 2002;  34 360-366
• 18 Peth J A, Kinnick T R, Youngblood E B, Tritschler H J, Henriksen E J. Effects of a unique conjugate of alpha-lipoic acid and gamma-linolenic acid on insulin action in obese Zucker rats.  Am J Physiol. 2000;  278 R453-R459
• 19 Chang S L, Lin J G, Chi T C, Liu I M, Cheng J T. An insulin-dependent hypoglycaemia induced by electroacupuncture at the Zhongwan (CV12) acupoint in diabetic rats.  Diabetologia. 1999;  42 250-255
• 20 Shulman G I. Cellular mechanisms of insulin resistance.  J Clin Invest. 2000;  106 171-176
• 21 Bessesen D H. The role of carbohydrates in insulin resistance.  J Nutr. 2001;  131 S2782-S2786
• 22 Higashiura K, Ura N, Takada T, Li Y, Torii T, Togashi N, Takada M, Takizawa H, Shimamoto K. The effects of an angiotensin-converting enzyme inhibitor and an angiotensin II receptor antagonist on insulin resistance in fructose-fed rats.  Am J Hypertens. 2000;  13 290-297
• 23 Carvalho E, Rondinone C, Smith U. Insulin resistance in fat cells from obese Zucker rats-evidence for an impaired activation and translocation of protein kinase B and glucose transporter 4.  Mol Cell Biol. 2000;  206 7-16
• 24 Bodkin N L, Pill J, Meyer K, Hansen B C. The effects of K-111, a new insulin-sensitizer, on metabolic syndrome in obese prediabetic rhesus monkeys.  Horm Metab Res. 2003;  35 617-624
• 25 de Vos P, Lefebvre A M, Miller S G, Guerre-Millo M, Wong K, Saladin R, Hamann L G, Staels B, Briggs M R, Auwerx J. Thiazolidinediones repress ob gene expression in rodents via activation of peroxisome proliferator-activated receptor gamma.  J Clin Invest. 1996;  98 1004-1009
• 26 Cheng J T, Liu I M, Hsu C F. Rapid induction of insulin resistance in opioid mu-receptor knock-out mice.  Neurosci Lett. 2003;  339 139-142
• 27 Radad K, Gille G, Moldzio R, Saito H, Ishige K, Rausch W D. Ginsenosides Rb1 and Rg1 effects on survival and neurite growth of MPP+-affected mesencephalic dopaminergic cells.  J Neural Transm. 2004;  111 37-45
• 28 Dey L, Xie J T, Wang A, Wu J, Maleckar S A, Yuan C S. Anti-hyperglycemic effects of ginseng: comparison between root and berry.  Phytomedicine. 2003;  10 600-605
• 29 Wasserman D H, Zinman B. Exercise in individuals with IDDM.  Diabetes Care. 1994;  17 924-937