Mechanism Of β-PGG In Galla Chinensis Inhibiting Apoptosis Of Islet β Cells In Hyperglycemia Induced By Environmental Factors

The incidence and prevalence of diabetes in the world has raised sharply.China has become the country with the largest number of diabetes in the world.Glucose toxicity caused by poor glycemic control is one of the important reasons of acute and chronic complications of diabetes.Apoptosis of pancreatic islet β cells is an important pathogenesis of type 1 and type 2 diabetes.INS-1 cells and islet β cells are prone to apoptosis in high glucose state,and islet β cell failure and various symptoms are induced.At present,the treatment of diabetes is Dipeptidylpeptidase-4(DPP-4),glucagon-likepeptide1(GLP-1),sodium-dependent glucose transporters 2(SGLT-2)and so on.It is of great value and significance to discover natural compounds that can protect islet β cells from glucose toxicity.Diabetes is a major public health problem that threatens human health and it is related to genetic factors and environmental factors.Environmental factors play an important role in the progression of individuals to diabetes.Recent data indicate that the prevalence of diabetes is related to air pollution.It is also related to environmental endocrine disruptors such as polyhalogenated aromatic hydrocarbons,organophosphorus pesticides,organochlorine pesticides,alkylphenols,heavy metals,dioxins,phthalates.In addition,the reduction in movement,obesity,and changes in dietary structure are the main environmental factors associated with diabetes.The changes in dietary structure are important parts of environmental factors such as high sugar,high fat,high calorie,and high precision,high purity diet.This research is mainly based on environmental factors,makes diabetes model through inducing the islet β-cell apoptosis caused by environmental factors and study the roles of β-PGG in Galla Chinensis inhibiting pancreatic islet β cell apoptosis,and slowing the occurrence and development of diabetes.Galla Chinensis is one of the traditional drugs for the treatment of diabetes,in which the component of polyphenolic compound β-PGG(1,2,3,4,6-penta-O-galloyl-β-D-glucose)is high.It is a representative of traditional Chinese medicine for the treatment of thirsty in diabetes.β-PGG is a polyphenol compound containing five galloyl groups and one molecule of glucose,which has anti-inflammatory,anti-allergic,anti-viral,anti-tumor and the other effects.Studies suggest that β-PGG can produce a certain hypoglycemic effect by inhibiting intestinal brush-likeα-glucosidase activity,reducing hepatic glucose output through mimicking insulin-like effects.The mechanism on β-PGG inhibiting the apoptosis of INS-1 cells and islet β cells in high glucose state is still unknown.The aim of this study is to explore the mechanism on β-PGG inhibiting the apoptosis induced by high glucose in INS-1 cells and islet β cells.The apoptotic rate of INS-1 cells under high glucose condition was determined by MTT assay and FCM method,and the change of rate of apoptosis after β-PGG treatment was detected.The model of Streptozocin(STZ)diabetes in Wistar diabetic rats was made and then β-PGG was administrated,the changes of islet and islet β cells in rats were detected by HE staining and orange-yellow G staining,and β cell apoptosis inhibited by β-PGG was determined.The expressions of mitochondrial stress,endoplasmic reticulum stress,NF-κB related factors in INS-1 cells and pancreatic tissues in Wistar STZ diabetic rats were detected by western blot and Real time-PCR.The main results of this study as following:(1)The rate of INS-1 cells apoptosis was increased under high glucose condition,and the apoptosis rate was decreased after adding β-PGG.The islet was atrophy and the number of islet was decreased induced by STZ,whereas the islet atrophy was attenuated and the number of islet beta cells was increased after β-PGG administration.(2)The expression of thioredoxin-interacting protein(TXNIP)was increased and thioredoxin-1(Trx-1)was decreased in INS-1 cells and islet β cells under high glucose state and in STZ model Wistar rats,whereas the expression of Trx-1 was reversed after β-PGG treatment.(3)The expressions of Caspase-9 and Cytc were increased in INS-1 cells and islet β cells under high glucose state and in STZ model Wistar rats,whereas the expressions of Caspase-9and Cytc were inhibited after β-PGG treatment.(4)The expressions of JNK and Caspase-12 were increased in INS-1 cells and islet β cells under high glucose state and in STZ model Wistar rats,whereas the expressions of JNK and Caspase-12 were inhibited after β-PGG treatment.(5)The expressions of NF-κB and IL-6 were increased in INS-1 cells and islet β cells under high glucose state and in STZ model Wistar rats,whereas the expressions of NF-κB and IL-6 were inhibited after β-PGG treatment.In conclusion: The oxidative stress,mitochondrial stress,endoplasmic reticulum stress,and NF-κB inflammtory response under high glucose state induced the apoptosis in INS-1 cells andislet β cells,whereas β-PGG in Galla Chinensis inhibited the above damages and the apoptosis in INS-1 cells and islet β cells.Thus,β-PGG may be used as one of the natural candidate compounds for the treatment of diabetes.