[Progress of researches on mechanisms of acupuncture therapy for insulin resistance].

Insulin resistance (IR) is a common pathophysiological basis of many chronic diseases, such as obesity, type 2 diabetes mellitus (T2DM), nonalcoholic fatty liver disease, cerebral vascular disease, cardiovascular and neurodegenerative diseases, etc. Acupuncture therapy has been demonstrated to have a positive role in reducing IR level in clinical practice. In the present paper, we summarized development of researches on the mechanism of acupuncture therapy underlying improvement of IR in recent 10 years from 1) regulating expression of hypothalamic phosphatidylinositol-3-kinase (PI3K)-p85 and PI3K-P110 proteins in obesity rats; 2) regulating the levels of some related proteins of insulin target tissues (liver and skeletal muscle), such as insulin receptor substrate-1 (IRS)-1 and -2, glucose transporter mRNAs and proteins, sterol regulatory element-binding protein 1 (SREBP-1) and fatty acid synthetase proteins; 3) suppressing inflammatory reaction of liver tissue and down-regulating serum adiponectin in T2DM rats; 4) raising the activity of superoxide dismutase (SOD) and reducing the levels of reactive oxygen species, and malondialdehyde (MDA) contents of quadriceps femoris in spontaneous IR rats; and 5) attenuating structural injury of pancreas islet and apoptosis of pancreatic ß cells in diabetes rats. Multi-levels and various systems of the neuro-endocrine-immune networks are involved in the actions of acupuncture in the improvement of IR. In the future, more attention should be paid to the study on the acupoint specificity, suitable acupoint combinations and stimulus parameters in clinical treatment of IR related various metabolic diseases, further optimizing clinical treatment protocols.

[Eletroacupuncture improves lipid metabolic disorder by regulating hepatic AMPK/p38 MAPK/RRARγ signaling in rats with high-fat diet-induced insulin resistance].

OBJECTIVE: To observe the effect of eletroacupuncture (EA) intervention on lipid metabolism and expression of AMP-activated kinase (AMPK), p38 mitogen-activated protein kinase (p38 MAPK) and peroxisome proliferator-activated receptor γ (PPARγ) protein in the liver in rats with insulin resistance (IR), so as to reveal its mechanisms underlying improvement of IR. METHODS: Forty male SD rats were randomly divided into blank control, model, medication, and EA groups (n＝8 in each). The IR model was established by feeding the rats with high-fat diet for 12 weeks. After successful establishment of model, the rats in the blank control group and model group were fixed in the self-made rat bag without receiving any treatment. The rats in the medication group were treated by gavage of pioglitazone (10 mL/kg). EA (2 Hz /100 Hz, 1 mA) was applied to bilateral "Fenglong"(ST40) and "Sanyinjiao"(SP6) for 20 min, once a day, for continuous 14 days for rats in the EA group. The ultrastructure of the liver tissue was observed by transmission electron microscope (TEM). Blood samples were taken from the abdominal aorta for detecting serum C-peptide (C-P), adiponectin (ADP), leptin (LEP) and resistin (RES) contents using enzyme linked immunosorbent assay (ELISA). The expression levels of AMPK, p38 MAPK and PPARγ proteins in the liver tissue were detected by Western blot. RESULTS: After modeling, the contents of serum C-P, LEP and RES, and the expression of liver p38 MAPK protein were significantly up-regulated (P<0.01, P<0.05), and the content of ADP and expression of AMPK and PPARγ significantly down-regulated in the model group compared with the blank control group (P<0.01). The increased contents of C-P, LEP and RES, and p38 MAPK protein expression and the decreased serum ADP and hepatic AMPK and PPARγ expression levels were completely reversed in both the EA and medication groups relevant to the model group (P<0.01, P<0.05). No significant differences were found between the EA and medication groups in up-regulating the levels of ADP, AMPK and PPARγ and in down-regulating the levels of C-P, LEP, RES and p38 MAPK(P>0.05). Outcomes of TEM showed that morphological structure of liver mitochondria was damaged, including a large number of lipid droplets, being blur in appearance, rupture of partial membrane, dissapearance of partial mitochondrial crests with vacuolus-like appearance and decrease of rough endoplasmic reticulum in the model group, which was relatively milder in both EA and medication groups. CONCLUSION: EA intervention is able to improve the disorder of lipid metabolism of IR rats, which may be associated with its effects in lowering the activity of fatty acid synthesis-related enzymes and regulating AMPK/p38 MAPK/PPARγ signaling to improve IR in the liver tissue.

[Effect of Eletroacupuncture Intervention on Insulin Resistance, Lipid Metabolic Disorder and Expression of Hepatic SREBP-1 c and Fatty Acid Synthase Proteins in Rats with Hyperlipidemia].

OBJECTIVE: To observe the effect of electroacupuncture(EA) of "Fenglong" (ST 40) and "Sanyinjiao" (SP 6) on lipid metabolic disorder, insulin resistance (IR) and expression of sterol regulatory element blinding protein-1 (SREBP-1) c and fatty acid synthase (FAS) proteins in the liver tissue in hyperlipidemia rats with IR, so as to reveal its mechanisms underlying improvement of IR. METHODS: Forty male SD rats were randomly divided into blank control, model, medication and EA groups (n＝8 in each group). The IR model was established by feeding the rat with high-fat diet. Rats of the medication group were treated by intragastric administration of pioglitazone (10 mL/kg). For rats of the EA group, EA (2 Hz/100 Hz，1 mA) was applied to bilateral ST 40 and SP 6, once daily for 14 days. The insulin sensitivity index (ISI) was assessed by calculating 60－120 min glucose infusion rate (GIR 60－120) with euglycemic hyperinsulinemic clamp in reference to Kraegen's and colleagues' methods. Fasting blood samples (10 mL) were collected and analyzed for fasting blood glucose (FBG) using enzyme method, serum fasting insulin(FINS) using ELISA, free fatty acid(FFA) using spectrophotometry, and total triglyceride(TG) and total cholesterol(TC) employing glycerine phosphate oxidase peroxidase (GPO-PAP) assay, low density lipoprotein(LDL), high density lipoprotein(HDL) levels using combined filiter paper activity and lipase activity methods, respectively. The IR level was assessed by calculating homeostatic model assessment of insulin resistance (HOMA-IR) using the formula (FBG×FINS)/22.5. The expression levels of SREBP-1 c and FAS proteins in the liver tissue were detected by Western blot. RESULTS: Following modeling, the GIR 60－120 and serum HDL were significantly decreased(P<0.01), and the HOMA-IR, serum FBG, FINS, FFA, TG, TC and LDL, and the expression levels of hepatic SREBP-1 c and FAS proteins were significantly increased in comparison with the blank control group(P<0.01). After the intervention, the decreased GIR 60－120 and serum HDL levels were considerably up-regulated (P<0.01), and the increased FBG, FINS, FFA, TG, TC and LDL, and hepatic SREBP-1 c and FAS protein levels were notably down-regulated in both EA and medication groups relevant to the model group (P<0.05, P<0.01). No significant differences were found between the EA and medication groups in all the indexes mentioned above (P>0.05). CONCLUSION: EA intervention is able to improve the disorder of lipid metabolism of IR rats, which may be associated with its effects in reducing the expression of SREBP-1 c and FAS proteins and in lowering the synthesis of fatty acid.

[Acupoints Selection Exploring for Acupuncture Treatment of Insulin Resistance Based on Data Mining].

OBJECTIVE: To analyze the characteristics and rules of acupoint selection for acupuncture treatment of insulin resistance. METHODS: Data collections were conducted by searching references on acupuncture treatment of insulin resistance in PubMed, CNKI, VIP data base from 1991 to 2016, and acupuncture prescription data base for acupuncture treatment of insulin resistance was established. Data mining was applied to analyze the characteristics and rules of acupoint selection. RESULTS: A total of 64 papers were recruited, and 73 acupoints were selected in these papers. It was found that the acupoints as Zusanli (ST 36), Sanyinjiao (SP 6), Fenglong (ST 40) and Taichong (LR 3) were used with highest frequencies. All acupoints selected distributed in 13 meridians, especially Foot Yangming Stomach Meridian, Foot Taiyin Bladder Meridian, and Conception Vessel with a total frequency of 58.07%. The special acupoints including five-shu points, eight confluent points and back-shu points, accounted for 56.71%. CONCLUSIONS: This study excavated the regular acupoint selection and acupoints compatibility for acupuncture treatment in patients with insulin resistance, giving evidence based confirming and direction for acupuncture clinical treatment.