Circular RNA PIP5K1A Promotes Glucose and Lipid Metabolism Disorders and Inflammation in Type 2 Diabetes Mellitus.

Disorders of glucose and lipid metabolism are an important cause of type 2 diabetes mellitus (T2DM). Identifying the molecular mechanism of metabolic disorders is key to the treatment of T2DM. The study was to investigate the effect of circRNA PIP5K1A (circPIP5K1A) on glucose and lipid metabolism and inflammation in T2DM rats. A T2DM rat model was established, and then the T2DM rats were injected with lentiviral vectors that interfere with circPIP5K1A, miR-552-3p, or ENO1 expression. Fasting blood glucose (FBG) and fasting insulin (FINS) levels of rats were detected by an automatic analyzer and insulin detection kit, and HOMA-IR was calculated. Lipid metabolism was assessed by measuring serum levels of TG, TC, LDL-C, leptin, and resistin. Serum levels of inflammatory factors (TNF-α and IL-6) were detected by ELISA. The pathological conditions of pancreatic tissue were observed by HE staining. circPIP5K1A, miR-552-3p and ENO1 levels were recorded. The experimental results showed that circPIP5K1A and ENO1 were up-regulated, and miR-552-3p was down-regulated in T2DM rats. Down-regulating circPIP5K1A or up-regulating miR-552-3p reduced blood glucose and lipid levels, inhibited inflammation, and improved pancreatic histopathological changes in T2DM rats. In addition, up-regulating ENO1 rescued the ameliorating effects of down-regulated circPIP5K1A on T2DM rats. In general, downregulating circPIP5K1A improves insulin resistance and lipid metabolism disorders and inhibits inflammation by targeting miR-552-3p to mediate ENO1 expression.

The hypoglycemic effect of eugenol on type 2 diabetic mice and regulation of signaling transduction pathway of glucose and lipid metabolism in liver / 中国药理学通报

Aim To study the effects of eugenol on hypoglycemic effect and hepatic glucose and lipid metabolism in type 2 diabetic mice, and to explore the possible mechanism. Methods The model of type 2 diabetes induced by long term high-fat diet was divided into four groups. The blood glucose and body weight of each group were measured once a week. After six weeks, the liver tissues of mice in each group were dissected and the liver mass and body mass of mice were weighed. Liver index, lipid metabolism and liver function were measured. Oral glucose tolerance test was performed. The levels of blood glucose, insulin, triglyceride, cholesterol, resistin, leptin, auxin, glucagon and plasminogen activator inhibitor-1 in serum were measured. He staining was used to observe the pathological changes of liver tissues. The expressions of SHP, pfoxo1, pCREB, PEPCK and G6Pase proteins in liver were detected by Western blot. Results Compared with HFD group, E40 group had lower body weight, smaller liver volume and healthy dark red. Compared with HFD group, E40 group decreased liver index, lipid metabolism and liver function. OGTT test showed that glucose tolerance was enhanced and the area under the curve was decreased in E40 group compared with HFD group. The levels of blood glucose, insulin, triglyceride, resistin, leptin, glucagon and plasminogen activator inhibitor-1 in E40 group were lower than those in HFD group. He staining showed that hepatocytes in HFD group were larger and accompanied with bullous steatosis than those in RD group. Hepatocyte steatosis and liver pathological state were significantly improved in E40 group. The results of Western blot showed that compared with HFD group, the expression of SHP, pfoxo1 and pCREB protein in E40 group was up-regulated, and the expression of PEPCK and G6Pase protein was down-regulated. Conclusions Eugenol can regulate the SHP/pFOXO1/PCREB/PEPCK/G6Pase signaling pathway, regulate glucose and lipid metabolism, inhibit insulin resistance, improve blood glucose level and glucose and lipid metabolism disorders in type 2 diabetes mellitus.

[Electroacupuncture improves glucose and lipid metabolism by regulating APN/AMPK/PPARα signaling of skeletal muscle in Zucker diabetic obese rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on skeletal muscle adiponectin receptor (Adipor1) / adenylate activated protein kinase (AMPK) / peroxisome proliferator-activated receptor α (PPARα) signaling pathway and skeletal muscle morphology by the secretion of serum adiponectin in Zucker diabetic obese (ZDF) rats, so as to explore its mechanism underlying regulating glucose and lipid metabolism of type 2 diabetes mellitus (T2DM) and improving skeletal muscle insulin resistance (IR). METHODS: Twelve male ZDF rats and six Zucker thin (ZL) rats were selected. The rats were fed with Purina#5008 high-fat diet for four weeks to induce T2DM model after adaptive feeding with normal diet for one week. The ZDF rats were randomly divided into model group and EA group according to blood glucose level after modeling and 6 ZL rats were used as the blank control group. Rats in the EA group were treated with "Pishu" (BL20), EA stimulation of "Yishu" (EX-B3), "Zusanli" (ST36) and "Sanyinjiao" (SP6), once a day and 6 times a week for 4 weeks. Rats of the model and blank control groups were grabbed and fixed in the same way as EA group. Fasting blood glucose (FBG) was measured before and after EA intervention. Serum levels of insulin (INS), C-peptide (C-P), adiponectin (APN) were measured by radioimmunoassay, and those of free fatty acid (FFA), low-density lipoprotein (LDL), cholesterol (TC), triglyceride (TG) content determined by enzyme colorimetry and insulin resistance index (HOMA-IR) was calculated. The protein expression levels of AdipoR1, AMPK and PPARα proteins in the quadriceps femoris tissues were detected by Western blot and histopathological changes of quadriceps femoris muscle were observed by H.E. staining. RESULTS: Compared with the blank control group, the levels of FBG, serum INS, C-P, FFA, LDL, TC, TG and HOMA-IR in the model group were significantly increased (P<0.01, P<0.05), while the levels of serum APN and the expressions of AdipoR1, AMPK and PPARα proteins in the skeletal muscle were significantly decreased (P<0.01, P<0.05). Compared with the model group, the levels of FBG, serum INS, C-P, FFA, LDL, TC and HOMA-IR in the EA group were significantly decreased (P<0.01), and those of serum APN and expression levels of AdipoR1, AMPK and PPARα proteins in the skeletal muscle significantly increased (P<0.01), but the serum TG level had no remarkable change in the EA group (P>0.05). In addition, H.E. staining showed disordered arrangement of skeletal muscle cells, rupture and fuzziness of muscle fibers, enlargement of the space between muscular fibers and infiltration of small number of adipose cells which were relatively milder in the EA group. CONCLUSION: EA can reduce blood glucose and lipid levels, and improve IR in ZDF rats, which may be related to its functions in up-regulating AdipoR1/AMPK/PPARα signaling and in promoting APN secretion.

Prediction of Gut Microbial Community Structure and Function in Polycystic Ovary Syndrome With High Low-Density Lipoprotein Cholesterol.

Gut microbiota has been proved to be involved in the occurrence and development of many diseases, such as type 2 diabetes, obesity, coronary heart disease, etcetera. It provides a new idea for the pathogenesis of polycystic ovary syndrome (PCOS). Our study showed that the gut microbial community of PCOS with high low-density lipoprotein cholesterol (LDLC) has a noticeable imbalance. Gut microbiota of PCOS patients was significantly changed compared with CON, and these changes were closely related to LDLC. Gut microbiota may affect the metabolic level of PCOS patients through multiple metabolic pathways, and lipid metabolism disorder may further aggravate the imbalance of gut microbiota. Actinomycetaceae, Enterobacteriaceae and Streptococcaceae had high accuracy in the diagnosis of PCOS and the differentiation of subgroups, suggesting that they may play an important role in the diagnosis and treatment of PCOS in the future. Also, the model we built showed good specificity and sensitivity for distinguishing PCOS from CON (including L_CON and L_PCOS, H_CON and H_PCOS). In conclusion, this is the first report on the gut microbiota of PCOS with high LDLC, suggesting that in the drug development or treatment of PCOS patients, the difference of gut microbiota in PCOS patients with different LDLC levels should be fully considered.