Study on relationship between expression of PKCα in glomeruli and development of nephropathy in diabetic rats

AIM:To observe the dynamic changes of expression of PKCα, TGF-β₁ and α-SMA in glomeruli of diabetic rats induced by the alloxon and to invesitigate their roles in the diabetic nephropathy(DN).METHODS:Rats were randomly divided into four groups: normal control group (group A), diabetic group of one week (group B), diabetic group of one month (group C), diabetic group of two months (group D). Immunohistochemistry and Western blotting were used to detect the expression of PKCα, TGF-β₁ and α-SMA in renal tissue of all groups. Blood glucose, triglycerides, cholesterol, creatinine and urine protein were analysed by chemical methods. The morphological changes of renal tissue were checked through microscopy.RESULTS:The expression of PKCα and TGF-β₁ in renal tissue of diabetic groups were increased comparing with those of nomal control group(P<0.05). The mesangial cells expressed α-SMA in two months group. Chronologically the expression of PKCα, TGF-β₁ and α-SMA were positively correlative with each other and the impairment of kidney was also observed.CONCLUSIONS: During the DN process the expression of PKCα increased. PKCα raised GFR and the permeability of glomerular filtration membrane which enhanced urinary albumin excretion. PKCα also increased expression of TGF-β and therefore to induce the expression of α-SMA. The appearance of α-SMA was a marker of the phenotypic transform of renal cells.     

Gene expression of 5α-reductase (type 2) in reproductive gland of pubertal diabetic rats

AIM: To study the molecular mechanism of reproduction dysfunction in pubertal diabetic rat, the level of 5α-reductase (type 2) mRNA in testis, epididymis and prostate in diabetic rat was detected. METHODS: The gene expression of 5α-reductase (type 2) was detected by Northern blot. RESULTS: In the caput of the epididymis, the expression of 5α-reductase (type 2) mRNA of D and ID groups was less than that of C group. CONCLUSION: The decreased expression of 5α-reductase (type 2) results in the decreased production of dihydrotestosterone, which influences the development and function of reproduction system in pubertal rats.     

The role of resistin in obesity and diabetes

Increased evidences indicate that resistin is a new hormone secreted from adipose tissue, it is reported to be an important signal molecule linking between obesity, insulin resistance and type 2 diabetes. Many factors can affect the gene expression of resistin. However, the detailed function of resistin still remains mysterious and much work needs to be undertaken.     

Protective effect of curcumin analogue L6H4 on diaphragm of type 2 diabetic rats

AIM: To investigate the protective effect of curcumin analogue L6H4 on diaphragm of type 2 diabetic rats.METHODS: SPF male Sprague-Dawley rats (n=40) were randomly divided into 5 groups: normal control (NC) group, high fat (HF) group, high fat+L6H4 treatment (FT) group, diabetes mellitus (DM) group and DM+L6H4 treatment (DT) group. The rats in the later 4 groups were fed with high-fat diet. After 4 weeks of high-fat diet fee-ding, the rats in DM and DT groups were intraperitoneally injected with streptozotocin to induce type 2 diabetes melliutus. The rats in FT and DT groups were given L6H4 by gavage for 8 weeks. Blood glucose and blood lipid levels were detected biochemically. Fasting serum insulin (FINS) level was measured by radioimmunoassay and insulin resistance index (HOMA-IR) was calculated. Serum adiponectin (APN) level was measured by ELISA. The morphological changes of the diaphragm were observed under light and transmission electron microscopes. Lipid deposition and the activity of succinate dehydrogenase (SDH) and NADH-tetrazolium reductase (NADH-TR) were observed by enzyme histochemical staining. The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in the diaphragm were measured by thiobarbituric acid method and hydroxylamine method, respectively. The protein expression of adiponectin receptor 1 (AdipoR1) in the diaphragm was determined by immunohistochemistry and Western blot. RESULTS: The levels of blood lipids, blood glucose, FINS and HOMA-IR in HF and DM groups were higher than those in NC group, but decreased after L6H4 treatment. The serum APN level in HF and DM groups was lower than that in NC group, but increased after treatment with L6H4. The muscle fibers of the diaphragm were shrunk, fat particles accumulated in the muscle fibers, and the mitochondria were slightly swollen in HF and DM groups. The diaphragmatic fibrosis was obvious in DM group. These lesions were relieved after L6H4 treatment. Compared with NC group, the level of MDA and the activity of SDH and NADH-TR in the diaphragm were increased in HF and DM groups, but decreased after treatment with L6H4. The activity of SOD and the expression of AdipoR1 in the diaphragm were lower than those in NC group, but increased after L6H4 treatment.CONCLUSION: The curcumin analogue L6H4 exerts a protective effect on diaphragm in type 2 diabetic rats. The strengthened protein expression of AdipoR1, the increased serum level of APN, and anti-lipid peroxidation may be involved in the process.     

Cell direct reprogramming：a new technique for treating diabetes

Diabetes is characterized by an absolute or relative deficiency in β-cell mass, which cannot be reversed with existing therapeutic strategies. The restoration of the endogenous islet β-cells can stabilize the level of blood glucose. The islet β-cells can be obtained from the directional differentiation of stem cells, but the process is complex and has the risk of teratomas generation. Cell direct reprogramming, one terminal differentiated cell can transdifferentiate into another kind of terminal differentiated cell, which is other than directional differentiation from stem cells. Direct reprogramming gives rise to the generation of islet β-cells from one terminal differentiated cell, may be preferable for diabetes therapy because of its unique advantage.     

Inhibition study of red rice polyphenols on pancreatic α-amylase activity by kinetic analysis and molecular docking

This study sought to investigate the possible inhibition mechanism of red rice polyphenols (RRP) on pancreatic α-amylase (PA) activity. RRP showed strong inhibition against PA activity and the half-inhibitory concentration (IC₅₀) value was 3.61 μg/mL. The fluorescence quenching of PA by RRP was a combination of static quenching and dynamic quenching. RRP could aggregate with PA and the physiochemical properties of the aggregates were closely related to the concentration of RRP. Kinetic analysis suggested that the inhibition mode of RRP on PA was reversible inhibition, which was a mixing of competitive inhibition and noncompetitive inhibition. Molecular docking speculated that RRP could form hydrogen bonds with PA by binding to the catalytic active sites (ASP197, GLU233 and ASP300) and the microenvironments of TRP58 and TRP59 were altered, thus inhibiting PA activity.     

Plasma leptin concentration in dogs: effects of body condition score, age, gender and breeds

Leptin is a cytokine produced by adipocytes, and plays a key role in the regulation of energy balance. In the present study, we measured plasma leptin concentrations of 166 normal and obese dogs visiting veterinary practices, and clarified the influence of age, gender and breed on plasma leptin levels in dogs. Leptin levels were higher in the dogs with higher body condition scores. There was no noticeable influence of age, gender and breed, but those in optimal puppies and obese Miniature Dachshund tended to be lower than those in corresponding groups. We conclude that plasma leptin is a reliable marker of adiposity in dogs regardless of age, gender and breed variations, and thereby useful as a blood biochemistry test for health examinations and treatment of obesity.