title: Chromium-containing traditional Chinese medicine, Tianmai Xiaoke Tablet improves blood glucose through activating insulin-signaling pathway and inhibiting PTP1B and PCK2 in diabetic rats.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: 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; xiaoxinhua@medmail.com.cn.
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Xiao
authors.affiliation: 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.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Miao
authors.initials: M
authors.lastname: Yu
authors.affiliation: 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.
authors.forename: Hua-Bing
authors.initials: HB
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Fan
authors.initials: F
authors.lastname: Ping
authors.affiliation: 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.
authors.forename: Zhi-Xin
authors.initials: ZX
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Jia
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis*; D002857:Chromium / Q000008:administration & dosage*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance; D008297:Male; D008516:Medicine, Chinese Traditional; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000037:antagonists & inhibitors*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D013607:Tablets
chemical_list: D001786:Blood Glucose; D007328:Insulin; D013607:Tablets; D002857:Chromium; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516610:Ptpn1 protein, rat; D019764:Phosphoenolpyruvate Carboxykinase (ATP)