DHM improves cognitive dysfunction in T2DM rats by inhibiting hippocampal endoplasmic reticulum stress / 中国药理学通报

Aim To investigate the effeet of dihydro- myricetin ( DHM ) on cognitive dysfunction in type 2 diabetes mellitus ( T2DM) rats and its mechanism.Methods SD rats were randomly divided into the normal control group ( n = 56) : normal diet and citrate buffer solution (30 mg • kg 1 ) ; T2DM model group (n =60) : high glucose, fat and low dose STZ ( 30 mg • kg 1 ) ( Four unsuccessful rats were eliminated ).Then rats in the above two groups were treated with or without DHM (250 mg • kg 1 • d intragastric).After 12 weeks, eight rats in each group were randomly selected to perform Morris water maze and Y maze test to observe the effect of DHM on cognitive function of rats.The remaining rats in each group were injected ERS antagonist tauroursodeoxycholic acid ( TUDCA ) 10 jxg • d 1 or ERS activator tunicamycin (TUN) 10 jxL, respectively.After the behavioral analysis, the hippocampal tissues of rats were taken out.The expressions of EH stress related proteins GRP78 and P- PERK were detected by Western blot.Results Both DHM and TUDCA could improve cognitive dysfunction in T2DM rats.On the contrary, TIJN reduced the effect of DHM on cognitive dysfunction in T2DM rats.TUDCA decreased the expression of GRP78 and p- PERK proteins in T2DM rats, while TUN increased the expression of GRP78 and p-PERK proteins in T2DM rats treated by DHM.Conclusion DHM improves cognitive dysfunction in T2DM rats, and the mechanism may be related to the inhibition of endoplasmic reticulum stress.

Effects and mechanism of stem cells from human exfoliated deciduous teeth combined with hyperbaric oxygen therapy in type 2 diabetic rats

OBJECTIVES: Mesenchymal stem cells (MSCs) are potentially ideal for type 2 diabetes treatment, owing to their multidirectional differentiation ability and immunomodulatory properties. Here we investigated whether the stem cells from human exfoliated deciduous teeth (SHED) in combination with hyperbaric oxygen (HBO) could treat type 2 diabetic rats, and explored the underlying mechanism. METHODS: SD rats were used to generate a type 2 diabetes model, which received stem cell therapy, HBO therapy, or both together. Before and after treatment, body weight, blood glucose, and serum insulin, blood lipid, pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6), and urinary proteins were measured and compared. After 6 weeks, rats were sacrificed and their organs were subjected to hematoxylin and eosin staining and immunofluorescence staining for insulin and glucagon; apoptosis and proliferation were analyzed in islet cells. Structural changes in islets were observed under an electron microscope. Expression levels of Pdx1, Ngn3, and Pax4 mRNAs in the pancreas were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: In comparison with diabetic mice, those treated with the combination or SHE therapy showed decreased blood glucose, insulin resistance, serum lipids, and pro-inflammatory cytokines and increased body weight and serum insulin. The morphology and structure of pancreatic islets improved, as evident from an increase in insulin-positive cells and a decrease in glucagon-positive cells. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining of islet cells revealed the decreased apoptosis index, while Ki67 and proliferating cell nuclear antigen staining showed increased proliferation index. Pancreatic expression of Pdx1, Ngn3, and Pax4 was upregulated. CONCLUSION: SHED combined with HBO therapy was effective for treating type 2 diabetic rats. The underlying mechanism may involve SHED-mediated increase in the proliferation and trans-differentiation of islet β-cells and decrease in pro-inflammatory cytokines and apoptosis of islets.

Effect of incRNA uc. 48 + on liver glycogen in type 2 diabetic rats / 中国药理学通报

Aim: To observe the effect of uc.48 + small interference RNA (siRNA) on liver glycogen abnormality in type 2 diabetic rats and its possible mechanism. Methods: The diabetes model was established by feeding high glucose and high fat diet combined with streptozotocin(STZ). After the success of the model, the long noncoding RNA uc. 48 + siRNA was injected into the rat body via tail vein. The changes of blood glucose and the content of liver glycogen were detected dynamically, and the liver glycogen was detected one week after injection. Glucokinase (GK) mRNA and protein expression in liver tissues of each group were detected by qPCR and Western blot. Results: It was observed that postprandial blood glucose and fasting blood glucose decreased in diabetic model rats after treated with uc. 48 + siRNA compared with those in model rats. The level of liver glycogen in diabetic model rats was significantly lower than that in control group. The synthesis of liver glycogen in diabetic model rats with uc. 48 + siRNA treatment increased compared with that in diabetic model group. The expressions of GK mRNA and protein in the diabetic model group were significantly lower than those in control group. The expression of GK mRNA and protein markedly increased after uc. 48 + siRNA treatment. Conclusions: uc. 48 + siRNA reduces blood glucose and increases glycogen synthesis in type 2 diabetic rats, and its mechanism may involve in increasing GK expression and Aktl phosphorylation.

Effects of anti-inflammatory drugs of diacerein on glucose and lipid metabolism in type 2 diabetic rats / 医学研究生学报

Objective Recent studies have shown that inflammatory cytokines are involved in the occurrence and development of diabetes mellitus .The article aimed to investigate the effects of anti-inflammatory drug--diacerein on hepatic PPAR-γand GLUT-2 protein expression and its role in the regulation of glucose and lipid metabolism in rats with type 2 diabetes mellitus ( T2DM) . Methods 55 male SD rats were randomly divided into 4 groups:normal control group (n=10), T2DM group (n=15), pioglitazone intervention group(n=15), and diacerein treatment group(n=15) .Rats in normal control group were fed with normal diet , the other 3 groups were fed with high fat diet .At the end of 8th experi-ment week, rats in 3 groups fed with high fat diet were treated with intraperitoneal injection of 30mg/kg streptozotocin ( STZ) solution, while rats in normal control group were injected with the same volume of sterile sodium citrate solution .At the end of 10th week, OGTT modeling rats were screened .Rats in pioglitazone intervention group were treated with 10 mg/kg pioglitazone by intragastric administra-tion, rats in diacerein group was treated with 50mg/kg diacerein by intragastric administration , and rats in normal control group and T2DM group were given the same volume of normal saline .The intervention lasted 4 weeks.At the end of 8th, 10th and 14th week, the blood examination of glycolipid , FINS, IL-1βand liver function indexes was done on fasting rats .Fourteenth weeks later , after getting blood samples , all rats were sacrificed and liver tissues were isolated .Western blot was applied in the detection of PPAR γand immu-nohistochemistry was applied to detect GLUT-2 protein in livers. Results At the end of 8th week, the FBG level in pioglitazone in-tervention group increased compared with normal control group ( P0 .05) show-ing higher levels compared with T 2DM group ( P<0.01).At 14th weekend, the GLUT-2 expression levels in normal control group (0.209±0.023), pioglitazone intervention group (0.226±0.017) and diacerein treatment group (0.232±0.012) were higher than that of T2DM group (0.173±0.009,P<0.01);and the GLUT-2 expression levels in pioglitazone intervention group and diacerein treatment group were higher than that of normal control group (P<0.05).The expression level of liver PPAR-γwas in positive correlation with those of GLUT-2 protein, HDL-C, FINS, ISI ( r=0.815, 0.780, 0.747, P<0.01) and in negative correlation with those of FBG , HbA1c, TC, TG, AST, ALT, IL-1β(r=-0.465,-5.716,-0.615,-0.675,-0.617,-0.521,-4.827, P<0.05). Conclusion Diacerein can enhance liver PPAR-γand GLUT-2 expression levels and reduce the levels of IL-1β, HbA1c and blood lipid, thus im-prove insulin resistance in T 2DM rats.

OPG and RANKL expression in alveolar bone of type 2 diabetic rats with periodontitis / 实用口腔医学杂志

Objective:To investigate the expression of osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) in type 2 diabetic rats with periodontitis.Methods:46 male Wistar rats were randomly divided into the healthy group(n =10),the periodontitis group(n =12),the type 2 diabetes mellitus group(n =12) and the type 2 diabetic periodontitis group(n =12).Animal models were prepared respectively.The expression of OPG and RANKL protein in alveolar bone was detected by immunohistochemistry(IHC).Results:Compared with the healthy group,the expression of OPG in the type 2 diabetes mellitus group,the periodontitis group,the type 2 diabetes mellitus with periodontitis group decreased in turn,however the expression of RANKL increased in turn.The expression of OPG and RANKL had no significant difference between periodontitis group and type 2 diabetes periodontitis group,while there was statistically significant difference among the other groups (P ＜ 0.05).Conclusion:Inflammation may lcad to upregulation of RANKL in osteoclasts and immune cells,and downregulation of OPG in osteoblasts.

Emblica officinalis improves glycemic status and oxidative stress in STZ induced type 2 diabetic model rats

OBJECTIVE@#To evaluate the antidiabetic and antioxidant potential of Emblica officinalis (E. officinalis) fruit on normal and type 2 diabetic rats.@*METHODS@#Type 2 diabetes was induced into the male Long-Evans rats. The rats were divided into nine groups including control groups receiving water, type 2 diabetic controls, type 2 diabetic rats treated with glibenclamide (T2GT) and type 2 diabetic rats treated with aqueous extract of fruit pulp of E. officinalis. They were fed orally for 8 weeks with a single feeding. Blood was collected by cutting the tail tip on 0 and 28 days and by decapitation on 56 day. Packed red blood cells and serum were used for evaluating different biochemical parameters.@*RESULTS@#Four weeks administration of aqueous extract of E. officinalis improved oral glucose tolerance in type 2 rats and after 8 weeks it caused significant (P<0.007) reduction in fasting serum glucose level compared to 0 day. Triglycerides decreased by 14% but there was no significant change in serum ALT, creatinine, cholesterol and insulin level in any group. Furthermore, reduced erythrocyte malondialdehyde level showed no significant change (P<0.07) but reduced glutathione content was found to be increased significantly (P<0.05).@*CONCLUSIONS@#The aqueous extract of E. officinalis has a promising antidiabetic and antioxidant properties and may be considered for further clinical studies in drug development.

Effect of Eplerenone, a Selective Aldosterone Blocker, on the Development of Diabetic Nephropathy in Type 2 Diabetic Rats

BACKGROUND: Aldosterone antagonists are reported to have beneficial effects on diabetic nephropathy by effective blocking of the renin-angiotensin-aldosterone system. We investigated the renoprotective effect of the selective aldosterone receptor blocker eplerenone, the angiotensin converting enzyme inhibitor lisinopril, and combined eplerenone and lisinopril treatment in type 2 diabetic rats. METHODS: Animals were divided into six groups as follows: Otsuka Long-Evans Tokushima Fatty (OLETF) rat control, OLETF rats treated with a low dose of eplerenone (50 mg/kg/day), OLETF rats treated with a high dose of eplerenone (200 mg/kg/day), OLETF rats treated with lisinopril (10 mg/kg/day), OLETF rats treated with a combination of both drugs (eplerenone 200 mg/kg/day and lisinopril 10 mg/kg/day), and obese non-diabetic Long-Evans Tokushima Otsuka rats for 26 weeks. RESULTS: Urinary albumin excretion was significantly lower in the lisinopril group, but not in the eplerenone group. Urinary albumin excretion was decreased in the combination group than in the lisinopril group. Glomerulosclerosis and renal expression of type I and type IV collagen, plasminogen activator inhibitor-1, transforming growth factor-beta1, connective tissue growth factor, and fibronectin mRNA were markedly decreased in the lisinopril, eplerenone, and combination groups. CONCLUSION: Eplerenone and lisinopril combination showed additional benefits on type 2 diabetic nephropathy compared to monotherapy of each drug.

Involvement of VEGF in both Cell Apoptosis and Survival in the Retina of Type 2 Diabetic OLETF Rats / 대한해부학회지

Vascular endothelial growth factor (VEGF) is closely involved in early retinal pathology of diabetes, including blood-retinal barrier breakdown, pericyte loss, neuro-retinal apoptosis, and cell proliferation. This study examines the involvement of VEGF in cell apoptosis and survival in the retina of animals with type 2 diabetes. We used retinas from 28-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of spontaneous type 2 diabetes, and Long-Evans Tokushima Otsuka (LETO) rats as controls. In parallel with evidence for pericyte loss, we found cell proliferation, apoptosis, and endothelial nitric oxide synthase (eNOS) (an indicator of endothelial cell proliferation/survival) and VEGF overexpression in the OLETF-retina, compared to control LETO. Furthermore, apoptotic signals were partly co-localized to only VEGF-positive cells in the OLETF-retina, but no apoptotic signals were found in VEGF- and eNOS-double-positive cells. These results suggest that upregulated VEGF is involved in apoptosis and eNOS-dependent cell survival in the retinas of type 2 diabetic rats.

Effect of diabetic neuropathy on renal 1-? hydroxylase and bone mineral density in old type 2 diabetic rats / 第三军医大学学报

Objective To investigate the change of renal 1-alpha hydroxylase and its effect on bone mineral density in the old rats with type 2 diabetic nephropathy. Methods Forty Wistar rats of 18 months old were randomly divided into normal control (N), diabetes (D), diabetes treated with vitamin D_ 3 (T1) and diabetes treated with 1-?(OH)D_ 3 (T2) groups, respectively. Ten rats in each group. Dual energy X-ray absorption (DEXA) was used to determine bone mineral density (BMD) of lumbar spines and femoral bone. 24 h urinary protein excretion, serum 25(OH)D_ 3 and 1,25(OH)_ 2 D_ 3 were measured by radioimmunoassay. Results Compared with controls, 24 h urinary protein excretion increased remarkably D, T1, T2 groups, while BMD greatly decreased, much lower in D group and T1 group than T2 group (P0.05). The level of 1,25(OH)_ 2 D_ 3 in N group was the same to T2 group, but higher than D, T1 groups (P