ABSTRACT
In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease (PD). However, difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1. Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains. CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and morphology. Importantly, PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and survival. Our findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD.
ABSTRACT
This article was aimed to study the effect ofQiwei granules on the podocyte in KK-Ay mice kidney. The 28 8-week-old male KK-Ay mice were randomly divided into the model group, low-dosage, middle-dosage and high-dosageQiwei granule group. Eight C57BL/6J mice were used as the normal control. The general conditions, blood glucose and 24 h albuminuria were recorded in the experiment. After 10-week treatment, renal indexes including serum creatinine and urea nitrogen were measured. The kidneys of mice were collected and measured. The hematoxylin and eosin (HE), Masson’s Trichrome, and periodic acid-Schiff (PAS) were used on renal tissues of mice. The immunohistochemical staining for WT-1 was made. Software analysis was combined in the calculation of renal podocyte amount. Western blot was used in the detection of nephrin protein expressions in the kidney of mice. RT-PCR was used in the detection of nephrin mRNA expression. The results showed that compared with the model group, the body weight, blood glucose, 24 h albuminuria and the serum creatinine were obviously decreased after 10-week treatment ofQiwei granules. It can effectively improve the glomerular mesangial proliferation and preserve the podocyte number. Meanwhile, after the treatment ofQiwei granules, the nephrin protein expression and mRNA expression were obviously higher than the model group. It was concluded thatQiwei granules probably managed nephrin expression to improve the podocyte injury in the diabetic nephropathy of KK-Ay mice.
ABSTRACT
This study was aimed to investigate the action mechanism ofHypoxis Hemerocallidea (African Potato, AP) on the AMPK signal pathway of skeletal muscles in diabetic rats. Among 40 male SD rats, 10 rats were used as the normal group, and the other 30 rats were fed with high-fat food for one month, and then injected with STZ for the model establishment. After the successful model establishment, rats were divided into the model group, pioglitazone hydrochloride group and the AP group. Intragastric administration was given for 5 weeks in each group. Then, the skeletal muscle tissues were embedded and sliced for immunohistochemistry test. The protein expression of p-AMPKα, p-AS16 and GLUT4 in skeletal muscles was detected by western blot. The 100 mmol·L-1 glucose was used in the establishment of C2C12 skeletal muscle cells insulin resistance model. AP drug-containing serum was used in the establishment of the treatment group. The control group was the normal cells. Glucose consumption, cell proliferation, SOD content, and MDA content were detected. And the protein expressions of p-AMPKα, p-AS160, GLUT4 were detected with the western blot and RT-PCR. The results showed that compared with the normal group, AP can up-regulate p-AMPKa protein express (P < 0.01), increase skeletal AS160 phosphorylation level (P < 0.01), and up-regulate the GLUT4 level (P < 0.01). Compared with the normal group, the high glucose caused the decrease of C2C12 skeletal muscle cell activity and the decrease of glucose consumption (P < 0.05), decrease of SOD, increase of MDA (P < 0.01), and the decrease of p-AMPKα, p-AS160, GLUT4 protein expression (P < 0.01). After 48 h intervention, the SOD of C2C12 skeletal muscle cells in the AP drug-containing serum group was significantly increased (P < 0.01), the MDA content was decreased (P < 0.05), the AMPKa and AS160 phosphorylation levels were increased (P < 0.01), the GLUT protein expression was increased (P < 0.01). It was concluded that the induced AMPKa and AS160 phosphorylation promoted GLUT 4 expression may be one of the action mechanism of insulin resistance of skeletal muscles in diabetes.
ABSTRACT
This study was aimed to observe the effect ofGuava leaf total flavonoids on HIT-T15 pancreaticβcell insulin resistance. Effective part of FSL was prepared. The dosing time, concentration and high glucose concentration of FSL were confirmed by observing HIT-T15 pancreaticβ cell growth curve and the influences of HIT-T15 pancreaticβ cell proliferation by different concentrations of glucose and FSL. Afterwards, the influence of FSL on HIT-T15 pancreaticβ cell insulin secretion, the expression of insulin receptor mRNA and insulin receptor substrate (IRS) 1 protein were measured under the environment of high glucose. The results showed that 50 mmol·L-1 glucose can significantly inhibit the proliferation of HIT-T15 pancreaticβ cell (P < 0.01). The 50μg·mL-1 FSL can significantly promote the proliferation of HIT-T15 pancreaticβ cells (P < 0.01), the insulin secretion (P < 0.05), the expression of insulin receptor mRNA (P < 0.05), and the protein expression of IRS 1 (P <0.01). It was concluded thatGuava leaf total flavonoids can promote the insulin secretion of HIT-T15 pancreaticβ cells under the circumstance of high concentration of glucose which may be related to its effect of increasing expression of insulin receptor mRNA and IRS-1 protein.
ABSTRACT
Guava leaf (GL) has been widely used as an herbal medicine for diabetes treatment in tropical and sub-tropical regions. GL has the function of drying dampness and fortifying the spleen, clearing heat and resolving toxins. Modern pharmacological study showed that GL contained flavonoid, phenolic acids, terpene, sesquiterpenoids and other chemical compounds, which regulated hyperglycemia. In recent years, the clinical and basic research on GL has received certain progress. This article reviewed effective components of GL, as well as research progress on clini-cal and basic research of type 2 diabetes.
ABSTRACT
Depending on the meaning and function of the liver in traditional Chinese medicine and modern medicine,this paper explores the important role of liver in the pathogenesis of DM (Diabetes Mellitus,DM).Combined with treatment based on syndrome differentiation and specific case report study,this paper has stressed the importance of treating DM from liver and so to set a sound basis for the systemic treatment based on syndrome differentiation from internal organs for DM.
ABSTRACT
Objective: To observe the effects of Tangnaikang (TNK), a compound traditional Chinese herbal medicine, on glucose metabolism and insulin resistance in obese Zucker rats. Methods: Twelve male obese Zucker rats, 6 weeks old, were randomly divided into control group and TNK group (3.24 g/kg) after being fed for 2 weeks. All rats received high-fat diet and 4-week treatment. Body weight and blood glucose were tested every week. Oral glucose tolerance test (OGTT) was performed and fasting insulin level was tested on days 0, 14 and 28. Triglyceride, cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and free fatty acids (FFA) were tested on day 28. Glucose infusion rate (GIR) was tested by hyperinsulinemic-euglycemic clamp from day 29. The protein expressions of protein kinase B (Akt), phospho-Akt (p-Akt) (Thr308) and glucose transporter protein 4 (GLUT4) in skeletal muscle and GLUT4 in adipose tissue were measured after hyperinsulinemic-euglycemic clamp test. Results: Compared with the control group, the fed blood glucose level and glucose level of OGTT at 120 min had a significant decline in TNK group on day 28, and TNK caused no alteration of the fasting serum insulin, and the GIR increased significantly in hyperinsulinemic-euglycemic clamp study. Furthermore, TNK increased Akt and p-Akt (Thr308) protein expressions in skeletal muscle and decreased the protein expression of GLUT4 in white adipose tissue. Body weight, and triglyceride, cholesterol, LDL-C and FFA contents were slightly decreased in the TNK group, but there were no statistically significant effects. Conclusion: TNK increases the protein expressions of Akt and p-Akt (Thr308) of the signal transduction pathway to influence the translocation of GLUT4 in skeletal muscle and improves glucose metabolism by reducing insulin resistance.