Abstract
In the clinical setting, given the potential adverse effects of thiazolidinediones and biguanides, we often have difficulty in treatment that no other insulin sensitizers are available for use in type 2 diabetic mellitus (T2DM) patients. Tianmai Xiaoke Pian (TMXKP) is a traditional Chinese medicine tablet, which is comprised of chromium picolinate, Tianhuafen, Maidong, and Wuweizi. To understand its mechanism of action on insulin resistance, TMXKP (50 mg/kg orally) was tested in T2DM rats (induced by a high-fat diet and streptozotocin). Eight weeks later, fasting blood glucose (FBG) and oral glucose tolerance tests (OGTT) were performed. Area under the curve (AUC) and homeostatic model assessment of insulin resistance (HOMA-IR) were calculated, and PI3-K/AKT signal pathway-related genes and proteins were tested by reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis in muscle, adipose, and liver tissues, respectively. TMXKP significantly reduced FBG, OGTT, AUC, and HOMA-IR in diabetic rats (P < 0.05). Furthermore, we also observed that TMXKP could significantly decrease IRS-1, IRS-2, PI3-K p85α, and AKT2 gene expression and also IRS-1, IRS-2, PI3-K, AKT2, and p-AKT2 protein expression levels (P < 0.05) in diabetic rats. These findings confirm that TMXKP can alleviate insulin resistance in T2DM rats through the PI3K/AKT pathway. Thus TMXKP appears to be a promising insulin sensitizer.
Highlights
Type 2 diabetes mellitus (T2DM) is a chronic metabolic syndrome with an increasing prevalence throughout the world
Fasting blood glucose and oral glucose tolerance tests (OGTT) were performed every 2 weeks after diagnosis of diabetes using blood samples taken from the tail vein
We observed a significant increase in protein concentrations in all tissues (P < 0.05, Figure 3). These findings indicate that insulin resistance (IR) was reduced by Tianmai Xiaoke Pian (TMXKP) through the PI3-K/AKT signal pathway
Summary
Type 2 diabetes mellitus (T2DM) is a chronic metabolic syndrome with an increasing prevalence throughout the world. To reduce IR, there are several insulin sensitizers that are commonly used, including thiazolidinediones (e.g., rosiglitazone and pioglitazone) and biguanides (e.g., metformin). These agents can improve IR and increase peripheral utilization of insulin, resulting in a decrease in blood glucose. In the clinical setting, we often face the difficulty of having no effective insulin sensitizers to use in certain T2DM patients, especially those who cannot tolerate biguanides. Journal of Diabetes Research the underlying mechanism of its antidiabetic effects remains unclear In this present study, we examined the effects of TMXKP on insulin downstream signaling PI3-K/AKT pathway, an important insulin pathway, in rats with T2DM
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