Ocular findings in Zucker Diabetic Fatty rats emphasize the key role of neuroglia degeneration in diabetic retinopathy pathophysiology

Diabetes mellitus is a leading cause of acquired vision loss and one of the world＇s fastest growing chronic diseases. Diabetic retinopathy （DR）, a specific complication of chronic hyperglycemia, is the leading cause of acquired vision loss worldwide in middle-aged and there- fore economically active people that also increases the medical and economic burden on the society （Klein, 2007）.

Danhong Huayu Koufuye combined with metformin attenuated diabetic retinopathy in Zucker diabetic fatty rats

AIM: To evaluate effects of Danhong Huayu Koufuye (DHK, a Chinese medicinal formulae) alone or combined with metformin on diabetic retinopathy (DR) in Zucker diabetic fatty (ZDF) rats, an animal model of obese type -2 diabetes, and then to investigate the mechanisms. METHODS: ZDF (fa/fa) rats were administered with vehicle (distilled water), metformin, DHK, and DHK plus metformin. Electrophysiological and histological analysis were applied to evaluated effects of DHK alone or combined with metformin on DR. The levels of fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) in blood were measured to evaluate the antihyperglycemic activity of DHK. Furthermore, levels of nitric oxide (NO), malondialdehyde (MDA) and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) in serum were measured to study effects of DHK on oxidative stress in ZDF rats. In addition, body weight, lipidic indexes and insulin level were also assessed. RESULTS: DHK combined with metformin significantly reversed the prolongation of latency times of flash electroretinogram (FERG) and oscillatory potentials (OPs) in diabetic rats. Furthermore, DHK alone or combined with metformin showed a remarkable suppression of retinal neovascularization and amelioration of retinal internal limiting membrane morphology. Moreover, DHK alone or plus metformin reduced FBG (P<0.05), HbA1c 1094 (P<0.01) and MDA (P<0.01) levels in diabetic rats. In addition, reductions in levels of triglycerides (TG) (P<0.01) and low density lipoprotein cholesterol (LDL-c) (P<0.01 and P<0.05, respectively) were also observed in diabetic rats treated with DHK alone or plus metformin. CONCLUSION: DHK in combination with metformin had a preventive and therapeutic effect on DR in type-2 diabetic rats, and the possible mechanisms may be alleviating hyperglycemia, reducing oxidative stress and improving lipid metabolism.

Effect of transcutaneous auricular vagus nerve stimulation on fasting blood glucose and serum insulin concentration in Zucker diabetes fatty rats

Objective:To observe the influence of transcutaneous auricular vagus nerve stimulation(taVNS) on fasting plasma glucose(FPG) and serum insulin(INS) in Zucker diabetes fatty(ZDF) rats and explore the regulatory effect of taVNS on blood glucose in ZDF rats.Methods:A total of 20 male ZDF rats were randomized into a model group and a taVNS group,10 rats in each one.Besides,the other 10 Zucker Lean(ZL) rats were selected to be a control group.The rats in the control group were fed with common forage and those in the model group and the taVNS group were fed with high-sugar and high-fat forage.The intervention of electric stimulation was applied in the rats of taVNS group,with 2/15 Hz in frequency,disperse-dense wave and 2 mA in intensity.Each intervention lasted 30 min,once a day,consecutively for 12 weeks.No any intervention was given in the control group and the model group.The body mass and FPG level were recorded once every 2 weeks in the rats.After the experiment,the rats were sacrificed and blood sample was collected.Enzyme linked immunosorbent assay(ELISA) was adopted to determine the level of serum INS in the rats.Results:After the modeling,compared with the control group,the body mass and FPG level were all higher(P <0.05,P <0.01) and the concentration of serum INS was lower(P <0.01) in the rats of the model group.After intervention,compared with the model group,the body mass was lower in week 6 to 10(P <0.01,P <0.05),FPG level was lower in week 8 to 12(P <0.01,P <0.05) and serum INS concentration was higher(P <0.01) in the rats of the taVNS group.Conclusion:TaVNS apparently improves in hyperglycemia in ZDF rats and increases serum insulin concentration in the rats.

Effects of a flavonoid-enriched orange peel extract against type 2 diabetes in the obese ZDF rat model

Effects of an enriched orange peel extract(OPE)against type 2 diabetes(T2D)were analyzed in ZDF rats which were hyperglycemic,dyslipidemic and express pro-inflammatory markers.Glucose related parameters were lowered in the lean control and metformin group as compared to ZDF vehicle controls.OPE was well tolerated and induced a decline in fasted blood glucose and increase levels of fed glucose although to a lesser degree as compared to metformin.However,OPE did not improve glucose tolerance but showed significantly elevated glucose levels.Furthermore,OPE treatment caused an increase of free fatty acids in a dose-responsive manner as well as elevated levels of cholesterol and LDL.The analysis of inflammatory mediators revealed a significant down-regulation of COX-2,ICAM-1,and TNF-˛in epididymal adipose tissue in response to OPE to a higher degree as compared to ibuprofen.In whole blood,IL-4 was upregulated in a dose-responsive manner as measured by ELISA.In summary,lipophilic OPE showed strong anti-inflammatory effects in adipose tissue,ambivalent effects against hyperglycemia,whereas hyperlipidemia was increased.Our study emphasize the complexity of anti-diabetic regimen suggesting a treatment with OPE to reduce inflammation in adipose tissue in combination with antidiabetic therapeutics as promising strategy against T2D.

Hypothyroidism affects astrocyte and microglial morphology in type 2 diabetes

In the present study, we investigated the effects of hypothyroidism on the morphology of astrocytes and microglia in the hippocampus of Zucker diabetic fatty rats and Zucker lean control rats. To induce hypothyroidism, Zucker lean control and Zucker diabetic fatty rats at 7 weeks of age orally received the vehicle or methimazole, an anti-thyroid drug, treatment for 5 weeks and were sacrificed at 12 weeks of age in all groups for blood chemistry and immunohistochemical staining. In the me- thimazole-treated Zucker lean control and Zucker diabetic fatty rats, the serum circulating triiodo- thyronine （T3） and thyroxine （＇I＂4） levels were significantly decreased compared to levels observed in the vehicle-treated Zucker lean control or Zucker diabetic fatty rats. This reduction was more prominent in the methimazole-treated Zucker diabetic fatty group. Glial fibrillary acidic protein im- munoreactive astrocytes and ionized calcium-binding adapter molecule 1 （Iba-1）-immunoreactive microglia in the Zucker lean control and Zucker diabetic fatty group were diffusely detected in the hippocampal CA1 region and dentate gyrus. There were no significant differences in the glial fibril- lary acidic protein and Iba-1 immunoreactivity in the CA1 region and dentate gyrus between Zucker lean control and Zucker diabetic fatty groups. However, in the methimazole-treated Zucker lean control and Zucker diabetic fatty groups, the processes of glial fibrillary acidic protein immunoreac- tive astrocytes and Iba-1 immunoreactive microglia, were significantly decreased in both the CA1 region and dentate gyrus compared to that in the vehicle-treated Zucker lean control and Zucker diabetic fatty groups. These results suggest that diabetes has no effect on the morphology of as- trocytes and microglia and that hypothyroidism during the onset of diabetes prominently reduces the processes of astrocytes and microglia.