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Journal of Integrative Medicine ›› 2014, Vol. 12 ›› Issue (3): 162-170.

• Research Article • Previous Articles     Next Articles

Chromium-containing traditional Chinese medicine, Tianmai Xiaoke Tablet improves blood glucose through activating insulin-signaling pathway and inhibiting PTP1B and PCK2 in diabetic rats

Qian Zhang, Xin-hua Xiao, Ming Li, Wen-hui Li, Miao Yu, Hua-bing Zhang, Fan Ping, Zhi-xin Wang, Jia Zheng    

  1. Key Laboratory of Endocrinology of Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
  • Received:2013-11-18 Revised:2014-02-21 Online:2014-05-10 Published:2014-05-15

OBJECTIVE: Chromium is an essential mineral that is thought to be necessary for normal glucose homeostasis. Numerous studies give evidence that chromium picolinate can modulate blood glucose and insulin resistance. The main ingredient of Tianmai Xiaoke (TMXK) Tablet is chromium picolinate. In China, TMXK Tablet is used to treat type 2 diabetes. This study investigated the effect of TMXK on glucose metabolism in diabetic rats to explore possible underlying molecular mechanisms for its action. METHODS: Diabetes was induced in rats by feeding a high-fat diet and subcutaneously injection with a single dose of streptozotocin (50 mg/kg, tail vein). One week after streptozotocin-injection, model rats were divided into diabetic group, low dose of TMXK group and high dose of TMXK group. Eight normal rats were used as normal control. After 8 weeks of treatment, skeletal muscle was obtained and was analyzed using Roche NimbleGen mRNA array and quantitative polymerase chain reaction (qPCR). Fasting blood glucose, oral glucose tolerance test and homeostasis model assessment of insulin resistance (HOMA-IR) index were also measured. RESULTS: The authors found that the administration of TMXK Tablet can reduce the fasting blood glucose and fasting insulin level and HOMA-IR index. The authors also found that 2 223 genes from skeletal muscle of the high-dose TMXK group had significant changes in expression (1 752 increased, 471 decreased). Based on Kyoto encyclopedia of genes and genomes pathway analysis, the most three significant pathways were “insulin signaling pathway”, “glycolysis/gluconeogenesis” and “citrate cycle (TCA)”. qPCR showed that relative levels of forkhead box O3 (FoxO3), phosphoenolpyruvate carboxykinase 2 (Pck2), and protein tyrosine phosphatase 1B (Ptp1b) were significantly decreased in the high-dose TMXK group, while v-akt murine thymoma viral oncogene homolog 1 (Akt1) and insulin receptor substrate 2 (Irs2) were increased. CONCLUSION: Our data show that TMXK Tablet reduces fasting glucose level and improves insulin resistance in diabetic rats. The mechanism may be linked to the inactivation of PTP1B and PCK enzymes, or through intracellular pathways, such as the insulin signaling pathway.

Key words: Chromium, Diabetes mellitus, Insulin signaling pathway, Glycolysis, Gluconeogenesis, TCA cycle, Rats


Figure 1

Body weight (A) and fasting blood glucose (B) before and after Tianmai Xiaoke Tablet treatment in rats (n=8, in each group) Data are represented as mean ± standard deviation. *P<0.05, **P<0.01, vs control group; △P<0.05, vs DM group.DM: diabetic model; TML: low dose of Tianmai Xiaoke Tablet; TMH: high dose of Tianmai Xiaoke Tablet."

Figure 2

The effect of Tianmai Xiaoke Tablet on oral glucose tolerance test blood glucose (A) and the area under curve (B) of rats (n=8, in each group) Data are represented as mean ± standard deviation. **P<0.01, vs control group; △P<0.05, vs DM group.DM: diabetic model; TML: low dose of Tianmai Xiaoke Tablet; TMH: high dose of Tianmai Xiaoke Tablet."

Figure 3

The effect of TMXK Tablet on FINS (A) and HOMA-IR (B) in rats (n=8, in each group) Data are represented as mean ± standard deviation. *P<0.05, **P<0.01, vs control group; △P<0.05, △△P<0.01, vs DM group.DM: diabetic model; TML: low dose of TMXK; TMH: high dose of TMXK. TMXK: Tianmai Xiaoke; FINS: fasting insulin; HOMA-IR: homeostasis model assessment of insulin resistance."




[1] O’Brien RM, Granner DK . Regulation of gene expression by insulin[J]. Physiol Rev, 1996,76(4):1109-1161
doi: 10.1152/physrev.1996.76.4.1109
[2] Yang W, Lu J, Weng J, Jia W, Ji L, Xiao J, Shan Z, Liu J, Tian H, Ji Q, Zhu D, Ge J, Lin L, Chen L, Guo X, Zhao Z, Li Q, Zhou Z, Shan G, He J; China National Diabetes and Metabolic Disorders Study Group.Prevalence of diabetes among men and women in China[J]. N Engl J Med, 2010,362(12):1090-1101
doi: 10.1056/NEJMoa0908292
[3] Nathan DM, Cleary PA, Backlund JY, Genuth SM, Lachin JM, Orchard TJ, Raskin P, Zinman B; DCCT/EDIC Study Research Group.Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes[J]. N Engl J Med, 2005,353(25):2643-2653
doi: 10.1056/NEJMoa052187
[4] Cefalu W, Hu F . Role of chromium in human health and in diabetes[J]. Diabetes Care, 2004,27(11):2741-2751
doi: 10.2337/diacare.27.11.2741
[5] Shao C, Lü XF, Xiao XH, Xu ZR, Yang ZJ, Wang P, Liu XL, Yang WY . Efficacy of Tianmaixiaoke tablets in the treatment of newly diagnosed type 2 diabetes mellitus in China[J]. Zhonghua Yi Xue Za Zhi, 2012,92(22):1522-1526
[6] Anderson RA, Cheng N, Bryden NA, Polansky MM, Cheng N, Chi J, Feng J . Elevated intakes of supplemental chromium improves glucose and insulin variables in individuals with type 2 diabetes[J]. Diabetes, 1997,46(11):1786-1791
doi: 10.2337/diab.46.11.1786
[7] Reed MJ, Meszaros K, Entes LJ, Claypool MD, Pinkett JG, Gadbois TM, Reaven GM . A new rat model of type 2 diabetes: the fat-fed, streptozotocin-treated rat[J]. Metabolism, 2000,49(11):1390-1394
doi: 10.1053/meta.2000.17721
[8] Huang JH, Huang XH, Chen ZY, Zheng QS, Sun RY . Dose conversion among different animals and healthy volunteers in pharmacological study[J]. Zhongguo Lin Chuang Yao Li Xue Yu Zhi Liao Xue, 2004,9(9):1069-1072
[9] Gao LH, Liu Q, Liu SN, Chen ZY, Li CN, Lei L, Sun SJ, Li LY, Liu JL, Shen ZF . A refined-Jinqi-Jiangtang tablet ameliorates prediabetes by reducing insulin resistance and improving β cell function in mice[J]. J Ethnopharmacol, 2014,151(1):675-685
doi: 10.1016/j.jep.2013.11.024
[10] Eisen MB, Spellman PT, Brown PO, Botstein D . Cluster analysis and display of genome-wide expression patterns[J]. Proc Natl Acad Sci U S A, 1998,95(25):14863-14868
[11] Dennis G Jr, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, Lempicki RA . DAVID: database for annotation, visualization, and integrated discovery[J]. Genome Biol, 2003,4(5):P3
doi: 10.1186/gb-2003-4-5-p3
[12] Hosack DA, Dennis G Jr, Sherman BT, Lane HC, Lempicki RA . Identifying biological themes within lists of genes with EASE[J]. Genome Biol, 2003,4(10):R70
doi: 10.1186/gb-2003-4-10-r70
[13] Livak KJ, Schmittgen TD . Analysis of relative gene expression data using real-time quantitative PCR and the 2-Δ ΔC(T) method[J]. Methods, 2001,25(4):402-408
doi: 10.1006/meth.2001.1262
[14] Anderson RA, Roussel AM, Zouari N, Mahjoub S, Matheau JM, Kerkeni A . Potential antioxidant effects or zinc and chromium supplementation in people with type 2 diabetes mellitus[J]. J Am Coll Nutr, 2001,20(3):212-218
doi: 10.1080/07315724.2001.10719034
[15] Kleefstra N, Houweling ST, Bakker SJ, Verhoeven S, Gans QO , Meyboorn-de Jong B, Bilo HJ.Chroumium treatment has no effect in patients with type 2 diabetes in a Western population: a randomized, double-blind, placebo-controlled trial[J]. Diabetes Care, 2007,30(5):1092-1096
doi: 10.2337/dc06-2192
[16] Komorowski J, Juturu V . Chromium supplementation does not improve glucose tolerance, insulin sensitivity, or lipid profile: a randomized, placebo-controlled, double-blind trial of supplementation in subjects with impaired glucose tolerance: response to Gunton et al[J]. Diabetes Care, 2005,28(7):1842-1843
doi: 10.2337/diacare.28.7.1842
[17] Albarrancin CA, Fugua BC, Evans JL, Goldfine ID . Chromium picolinate and biotin combination improves glucose metabolism in treated, uncontrolled overweight to obese patients with type 2 diabetes[J]. Diabetes Metab Res Rev, 2008,24(1):41-51
doi: 10.1002/(ISSN)1520-7560
[18] Martin J, Wang ZQ, Zhang XH, Wachtel D, Volaufova J, Matthews DE, Cefalu WT . Chromium picolinate supplementation attenuates body weight gain and increase insulin sensitivity in subjects with type 2 diabetes[J]. Diabetes Care, 2006,29(8):1826-1832
doi: 10.2337/dc06-0254
[19] Wang ZQ, Zhang XH, Russell JC, Hulver M, Cefalu WT . Chromium picolinate enhance skeletal muscle cellular insulin signaling in vivo in obese, insulin-resistant JCR: LA-cp rats[J]. J Nutr, 2006,136(2):415-420
doi: 10.1093/jn/136.2.415
[20] Yang X, Li SY, Dong F, Ren J, Sreejayan N . Insulin-sensitizing and cholesterol-lowering effects of chromium(D-Phenylalanine)3[J]. J Inorg Biochem, 2006,100(7):1187-1193
doi: 10.1016/j.jinorgbio.2006.01.039
[21] Elchebly M, Payette P, Michaliszyn E, Cromlish W, Collins S, Loy AL, Normandin D, Cheng A, Himms-Hagen J, Chan CC, Ramachandran C, Gresser MJ, Tremblay ML, Kenedy BP . Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene[J]. Science, 1999,283(5407):1544-1548
doi: 10.1126/science.283.5407.1544
[22] Klaman LD, Boss O, Peroni OD, Kim JK, Martino JL, Zabolotny JM, Moghal N, Lubkin M, Kin YB, Sharpe AH, Stricker-Krongrad A, Shulman GI, Neel BG, Kahn BB . Increased energy expenditure, decreased adiposity, and tissue-specific insulin sensitivity in protein-tyrosine phosphatase 1B-deficient mice[J]. Mol Cell Biol, 2000,20(15):5479-5489
doi: 10.1128/MCB.20.15.5479-5489.2000
[23] Zinker BA, Rondinone CM, Trevillyan JM, Gum RJ, Clampit JE, Waring JF, Xie N, Wilcos D, Jacobson P, Frost L, Kroeger PE, Reilly RM, Koterski S, Opgenorth TJ, Ulrich RG, Crosby S, Butler M, Murray SF , McKay RA, Bhanor S, Monia BP, Jirousek MR.PTP1B antisense oligonucleotide lowers PTP1B protein, normalizes blood glucose, and improves insulin sensitivity in diabetic mice[J]. Proc Natl Acad Sci U S A, 2002,99(17):11357-11362
doi: 10.1073/pnas.142298199
[24] Gum RJ, Gaede LL, Koterski SL, Heindel M, Clampit JE, Zinker BA, Trevillyan JM, Ulrich RG, Jirousek MR, Rondinone CM . Reduction of protein tyrosine phosphatase 1B increases insulin-dependent signaling in ob/ob mice[J]. Diabetes, 2003,52(1):21-28
doi: 10.2337/diabetes.52.1.21
[25] Consdi A, Nurjhan N . Contribution of gluconeogenesis to overall glucose output in diabetic and nondiabetic men[J]. Ann Med, 1990,22(3):191-195
doi: 10.3109/07853899009147268
[26] Valera A, Pujol A, Pelegrin M, Bosch F . Transgenic mice overexpressing phosphoenolpyruvate carboxykinase develop non-insulin-dependent diabetes[J]. Proc Natl Acad Sci U S A, 1994,91(19):9151-9154
doi: 10.1073/pnas.91.19.9151
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