[α-lipoic acid ameliorates liver injury in rats with type 2 diabetes mellitus via activating AMPK/mTOR pathway].

OBJECTIVE: To investigate the effect of α-lipoic acid in ameliorating liver injury in rats with type 2 diabetes mellitus via activating adenosine 5'-monophosphate-activate protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway. METHODS: The T2DM rat models were established by feeding with high-fat, high-sucrose diet and intraperitoneal injection of 27.5 mg/(kg·d) streptozotocin. The 32 rats with T2DM were randomly divided into 4 groups: T2DM group, α-lipoic acid group (LA), Compound C group (Comp C, an inhibitor of AMPK) and LA+Comp C group, with 8 rats in each group. Additionally, 8 Sprague-Dawlay (SD) rats without diabetes were set as normal control. The rats received α-lipoic acid at a dosage of 100 mg/(kg·d) or Compound C at a dosage of 20 mg/(kg·d) by intraperitoneal injection for 8 weeks as needed. The levels of relevant biochemical indexes were detected. The weight of liver was recorded to calculate liver weight index (LWI), and the pathological changes of liver tissues were detected by light and electron microscopy. The levels of AMPK, p-AMPK, mTOR, p-mTOR in rat liver were detected by Western blot. RESULTS: Compared with control group, the levels of LWI, homeostasis model assessment of insulin resistance, fasting blood glucose, alanine transaminase, aspartate transaminase, gamma glutamyl transferase and triglyceride in T2DM group were increased significantly (all P＜0.05). The liver tissue lesions were more serious and hepatic steatosis grade was higher. The expression of p-AMPK was decreased (P＜0.05) and the expression of p-mTOR was increased significantly(P＜0.05). α-lipoic acid could reverse the above-mentioned changes, ameliorate insulin resistance (all P＜0.05), protect the structure and function of liver, and activate the AMPK/mTOR pathway (P＜0.05). The protection of α-lipoic acid was weakened by the inhibition of AMPK with Compound C (P＜0.05). CONCLUSION: α-lipoic acid could protect the liver of rats with T2DM by activating AMPK/mTOR pathway.

Azithromycin inhibited oxidative stress and apoptosis of high glucose-induced podocytes by inhibiting STAT1 pathway.

Azithromycin (AZM) has a therapeutic effect on diabetes, but there is no report on whether AZM has a therapeutic effect on diabetic nephropathy (DN) and its specific mechanism. Cell survival was detected by CCK-8. The expression of the inflammatory factors TNF-α, IL-1ß, and IL-6 was determined by ELISA. The expression of inflammatory proteins MCP-1, NLPR3, and ASC was detected by western blot. The expression of MDA, LDH, and SOD was detected by the appropriate kit. Apoptosis was detected by flow cytometry and apoptosis-related proteins Bcl-2, Bax, Caspase-3, 6, 9, and Cleaved caspase-3, 6, 9 were detected by western blot. In addition, the expression of STAT1 was detected by western blot. AZM can increase the activity of high glucose-induced podocytes (p < .05). After high glucose induction, the expression of TNF-α, IL-1ß, and IL-6 was increased and the expression of MCP-1, NLPR3, and ASC proteins was also increased (p < .001). When AZM was added, the expression of all the above-mentioned proteins was decreased (p < .001). In addition, MDA, LDH, and SOD were increased after high glucose induction, while decreased after AZM treatment (p < .001). AZM can inhibit apoptosis and the expression of Bax and Cleaved caspase-3, 6, 9, and promote the expression of Bcl-2 (p < .001). Furthermore, the expression of STAT1 was increased after high glucose induction, while the expression of STAT1 was decreased after AZM action (p < .01). By adding a STAT1 agonist IFN-γ, the effects of AZM on inflammation, oxidative stress, and apoptosis of high glucose-induced podocytes were inhibited (p < .05). AZM inhibited inflammation, oxidative stress, and apoptosis of high glucose-induced podocytes by inhibiting STAT1 pathway.

Plantar Pressure Changes and Correlating Risk Factors in Chinese Patients with Type 2 Diabetes: Preliminary 2-year Results of a Prospective Study.

BACKGROUND: Plantar pressure serves as a key factor for predicting ulceration in the feet of diabetes patients. We designed this study to analyze plantar pressure changes and correlating risk factors in Chinese patients with type 2 diabetes. METHODS: We recruited 65 patients with type 2 diabetes. They were invited to participate in the second wave 2 years later. The patients completed identical examinations at the baseline point and 2 years later. We obtained maximum force, maximum pressure, impulse, pressure-time integral, and loading rate values from 10 foot regions. We collected data on six history-based variables, six anthropometric variables, and four metabolic variables of the patients. RESULTS: Over the course of the study, significant plantar pressure increases in some forefoot portions were identified (P < 0.05), especially in the second to forth metatarsal heads. Decreases in heel impulse and pressure-time integral levels were also found (P < 0.05). Plantar pressure parameters increased with body mass index (BMI) levels. Hemoglobin A1c (HbA1c) changes were positively correlated with maximum force (ß = 0.364, P = 0.001) and maximum pressure (ß = 0.366, P = 0.002) changes in the first metatarsal head. Cholesterol changes were positively correlated with impulse changes in the lateral portion of the heel (ß = 0.179, P = 0.072) and pressure-time integral changes in the second metatarsal head (ß = 0.236, P = 0.020). Ankle-brachial index (ABI) changes were positively correlated with maximum force changes in the first metatarsal head (ß = 0.137, P = 0.048). Neuropathy symptom score (NSS) and common peroneal nerve sensory nerve conduction velocity (SCV) changes were positively correlated with some plantar pressure changes. In addition, plantar pressure changes had a correlation with the appearance of infections, blisters (ß = 0.244, P = 0.014), and calluses over the course of the study. CONCLUSIONS: We should pay attention to the BMI, HbA1c, cholesterol, ABI, SCV, and NSS changes in the process of preventing high plantar pressure and ulceration. Some associated precautions may be taken with the appearance of infections, blisters, and calluses.

Risk factors correlated with plantar pressure in Chinese patients with type 2 diabetes.

BACKGROUND: Plantar pressure is a key factor for predicting ulceration in the foot of a diabetes patient. SUBJECTS AND METHODS: We recruited a group of 100 Chinese patients with type 2 diabetes and an age-, sex-, weight-, and height-matched group of 100 Chinese subjects without diabetes. We obtained plantar pressure data using a Footscan(®) gait system (RsScan International, Olen, Belgium) when the subjects with and without diabetes walked barefoot across a sensor platform. We recorded the maximum force, maximum pressure, impulse, pressure-time integral, and loading rate from 10 regions of the foot. We collected the data of 11 history-based variables, 10 anthropometric variables, and three metabolic variables regarding the clinical characteristics of the diabetes patients. RESULTS: Weight was identified as a determining factor for high plantar pressure. Height, the Neuropathy Symptom Score (NSS), and ankle-brachial index (ABI) were correlated positively with plantar pressure measurements, respectively. The sex, history of ulcer and callus, intima-media membrane of the lower limb blood vessels, and fasting blood glucose (FBG) could also explain a portion of the variability of the plantar pressure measurements. However, the correlations were low or weak. CONCLUSIONS: High plantar pressure in diabetes patients could be predicted, in part, based on weight, height, NSS, ABI, sex, history of ulcer and callus, intima-media membrane of the lower limb blood vessels, and FBG. Therefore, interventions should be taken specifically before high plantar pressure emerges.

[Effects of Astragalus and saponins of Panax notoginseng on MMP-9 in patients with type 2 diabetic macroangiopathy].

OBJECTIVE: To investigate the role and mechanism of Astragalus (AS) and saponins of Panax notoginseng (PNS) in treating type 2 diabetic macroangiopathy. METHOD: 94 patients with type 2 diabetic macroangiopathy were divided into two groups randomly: group treated with Simvastatin and group treated with AS and PNS, compared with 40 healthy control subjects. Serum level of MMP-9 and lipid in patients and healthy subjects were measured before and after treatment. RESULT: The serum levels of MMP-9, TG, TC, LDL-C, VLDL-C in patients with type 2 diabetic macroangiopathy were improved, while the levels of HDL-C were decreased. Like Simvastatin AS and PNS had the function of reducing MMP-9 and accommodating lipid metabolism. CONCLUSION: Besides accommodating lipid metabolism, AS and PNS can also reduce the level of serum MMP-9 soas to treat type 2 diabetic macroangiopathy.