| Along with economic development,people eat more and do exercise less than before,the attack rate and case rate of type 2 diabetes are increasing, those bring heavy burden for our society.The role of insulin resistance (IR) in type 2 diabetes, the most frequently encountered metabolic disorder in the world, has attracted much attention in recent years.ObjectivesOn basis of clinical treatment of insulin resistance (IR) in type 2 Diabetes with Tradition Chinese Medicine(TCM)and Material medica, this study applies Neijing theory"Excessive fire consuming qi"into the clinical and laboratory researches and points out that there is fire consuming qi in the pathogenesis of IR of type 2 Diabetes , therefore purging fire together with invigorating qi can be used to treat it, according to"treating heat with cold". In this study, we observed the effect of huanglian (Rhizoma Coptidis)-renshen (Radix Ginseng)-pair on IR and secondaryβcell function damage in mice with laboratory type 2 diabetes to explore its pathogenesis and treatment and thus provide foundation for innovation in TCM theory on treating IR with Traditional Chinese Medicine and material medica.Methods1. Literature studies: All recent relevant literature concerning Type 2 diabetes, IR, PPARγand animal experiments are documented. So this study has taken a full account of the mechanism, experimental and clinical studies of IR in type 2 diabetes into consideration both in TCM and allopathic medicine and made a systematic review of PPARγadvancements and animal experiments.2. Theoretical Studies: Under the guidance of TCM theory, we maintain that the treatment of IR is decisive in TCM treatment of type 2 diabetes. After reviewing the status quo of the clinical application of purging fire together with invigorating qi in treating IR, we elucidate the TCM pathogenesis of IR in type 2 diabetes and put forward the hypothesis that there is excessive fire consuming qi in the pathogenesis of IR, and that we should combine purging fire with invigorating qi in IR treatment. We, however, consider it more significant to explore effective clinical treatment of IR rather than theoretical studies to enrich TCM theory of IR in type 2 diabetes.3. Laboratory studiesWe rendered mice insulin resistant and diabetic by feeding high glucose and fat diet together with peritoneal injection of STZ and then treated it with QingReYiQi drug, comparing to Pioglitazone. Then we observed the effects of the drugs on glycometabolism, lipid metabolism, insulin sensitivity and pancreas pathomorpholgoy, serum TNF-α, FFA and genetic expression of PPARγin IR mice.Results①Evaluation of animal model: We succeeded in rendering laboratory IR of type 2 diabetes, manifested as hyperglycemia, hyperinsulinemia, high level of free fatty acid and TNF-αwith a significant lower level of IAI. So the mice did get IR and damage ofβcell function as well, in accordance with the clinical features of type 2 diabetes. With drug interference, the laboratory results are improved correspondingly, proving the animal model valid, practicable, economic and successful with a low death rate, thus an ideal model for study of IR and type 2 diabetes.②Study of pharmacodynamics action and drug safety: We observed the effects of QingReYiQi drug on glycometabolism, lipid metabolism, pathopharmocology and liver function of IR mice of laboratory type 2 diabetes.Serum tests of glycometabolism showed that QingReYiQi drug can significantly lower fasting blood sugar and insulin and thus improve IR condition, similar to the effect of pioglitazone.Serum tests of lipid metabolism showed that QingReYiQi drug can significantly lower the level of serum cholesterol,triglyceride and low-density lipoprotein and increase high-density lipoprotein level. Their function in regulating lipid metabolism is comparable to that of hydrochloric acid pioglitazone.The staining of pancreas shows that QingReYiQi drug can improve pancreatic injury in IR mice induced by long-term high-glucose-high-fat diet with STZ abdominal injection, such as decreased pancreatic islets, deformed pancreatic cells, degranulation, collapse or absence ofβcells. Immunohistochemistry study ofβcell also proves it.Serum test of liver function proves the safety of QingReYiQi drug.③Mechanism probation : mechanism of drug action has been probed on the basis of pharmacodynamics research.Immunohistochemistry study of the effect of QingReYiQi drug on serum TNF-αin IR mice with labarotary type 2 diabetes shows that QingReYiQi drug can significantly reduce serum TNF-αlevel, comparable to hydrochloric acid pioglitazone, indicating that the pair may enhance sensitivity of insulin by lowering TNF-α, preventing TNF-αfrom inhibiting the expression of GLUT4 in fat and muscle cells autophosphorylating of insulin receptor or inhibiting of second messenger's activation and promoting the breakdown of fat.Chromometry studies of the effect of the pair on serum FFA in IR mice with labarotory type 2 diabetes indicates that the pair can significantly lower serum FFA, comparable to hydrochloric acid pioglitazone. The findings suggest that the pair may improve IR, glucometabolism and lipid metabolism by reducing the harm of lipid to the body.Western-blotting product semiquantitative study of the effects of the pair on the expression of PPARγin IR mice with laboratory type 2 diabetes indicates that the pair can promote the expression of PPARγin labarotory mice, the function of which is comparable to hydrochloric acid pioglitazone. The findings indicate that QingReYiQi drug may act in a similar way to hydrochloric acid pioglitazone by activating PPARγ, slowing the release of FFA, enhancing the sensitivity of skeletal muscle and liver to insulin, reducing the exportation of glycogen and promoting the utilization of glucose in skeletal muscle so as to lower blood sugar level.ConclusionsThis study explores the mechanism of QingReYiQi drug in treating IR in type 2 diabetes on a multitarget and multi-element basis. Besides, it makes effective probation into the TCM study of IR in type 2 diabetes and its mechanism. Meanwhile, this study primarily proves the pathogenesis of"excessive fire consuming qi"and treatment of"purging fire with invigorating qi", thus it provides an innovative way to study the role of TCM in treating IR and protectingβcells in type 2 diabetes. |
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