scholarly journals Artesunate Combined With Metformin Ameliorate on Diabetes-Induced Xerostomia by Mitigating Superior Salivatory Nucleus and Salivary Glands Injury in Type 2 Diabetic Rats via the PI3K/AKT Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Siqin Zhang ◽  
Jiarui Li ◽  
Xiaolin Nong ◽  
Yuxiang Zhan ◽  
Jiazhi Xu ◽  
...  
Keyword(s):  
Urine Volume ◽  
Underlying Mechanism ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Akt Pathway ◽  
Control Group ◽  
Sprague Dawley ◽  
Bdnf Expression ◽  
Parasympathetic Innervation

Polydipsia and xerostomia are the most common complications that seriously affect oral health in patients with diabetes. However, to date, there is no effective treatment for diabetic xerostomia. Recent studies have reported that artesunate (ART) and metformin (Met) improve salivary gland (SG) hypofunction in murine Sjögren’s syndrome. Therefore, aim of this study was to investigate the effect and underlying mechanism of artesunate (ART) alone and in combination with metformin (Met) on hyposalivation in type 2 diabetes mellitus (T2DM) rats. T2DM rats were induced using a high-fat diet and streptozotocin. SPF male Sprague–Dawley rats were divided into the following five groups: normal control group, untreated diabetic group, ART-treated diabetic group (50 mg/kg), Met-treated diabetic group (150 mg/kg), and ART/Met co-treated diabetic group (50 mg/kg ART and 150 mg/kg Met). ART and Met were intragastrically administered daily for 4 weeks. The general conditions, diabetes parameters and serum lipids were evaluated after drug treatment. Furthermore, we observed changes in the central superior salivatory nucleus (SSN) and SG, and changes in the AQP5 expression, parasympathetic innervation (AChE and BDNF expression), and PI3K/AKT pathway- (p-AKT, and p-PI3K), apoptosis- (Bax, Bcl-2, and Caspase3), and autophagy- (LC3 and P62) related markers expression in T2DM rats after treatment. Our results showed that ART or Met alone and ART/Met combination attenuated a range of diabetic symptoms, including weight loss, urine volume increase, water consumption increase, hyperglycemia, insulin resistance, glucose intolerance and dyslipidemia. More importantly, we found that these three treatments, especially ART/Met combination, mitigated hyposalivation in the T2DM rats via improving the central SSN and SGs damage in hyperglycemia. Our data also indicated that ART/Met attenuated SG damage though regulating the PI3K/Akt pathway to inhibit apoptosis and autophagy of SGs in the T2DM rats. Moreover, ART/Met preserved parasympathetic innervation (AChE and BDNF expression) in SGs to alleviate diabetes-induced hyposalivation likely through rescuing central SSN damage. Taken together, these findings might provide a novel rationale and treatment strategy for future treatment of diabetes-induced xerostomia in the clinic.

scholarly journals IMPROVEMENT IN OXIDATIVE STRESS AFTER DUODENOJEJUNOSTOMY IN AN EXPERIMENTAL MODEL OF TYPE 2 DIABETES MELLITUS

2016 ◽  
Vol 29 (suppl 1) ◽  
pp. 3-7 ◽  
Author(s):  
Cacio Ricardo WIETZYCOSKI ◽  
João Caetano Dallegrave MARCHESINI ◽  
Sultan AL-THEMYAT ◽  
Fabiola Shons MEYER ◽  
Manoel Roberto Maciel TRINDADE
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Control Group ◽  
Oral Glucose ◽  
Surgical Group

ABSTRACT Background: Type 2 Diabetes Mellitus is a multifactorial syndrome with severe complications. Oxidative stress is accepted as a causal factor of chronic complications Aim: To demonstrate alterations in oxidative stress after metabolic surgery. Methods: Twenty-four 2-day-old Wistar rats were used. In 16, Type 2 Diabetes Mellitus was induced by 100 mg/kg streptozotocin injection. The development of diabetes was confirmed after 10 weeks using an oral glucose tolerance test. Eight diabetic rats composed the diabetic surgical group; the remaining eight composed the diabetic group. Eight animals in which diabetes was not induced formed the clinical control group. The Marchesini technique was used in the diabetic surgical group. After 90 days, the rats were sacrificed, and the oxidative stress markers were measured. Results: Thiobarbituric acid reactive substances, superoxide dismutase and catalase were significantly reduced in the diabetic surgical group compared to the diabetic group. Conclusion: The duodenojejunostomy was effective in controlling the exacerbated oxidative stress present in diabetic rats.

scholarly journals Cyclosporine-A Attenuates Retinal Inflammation by Inhibiting HMGB-1 Formation in Rats with Type 2 Diabetes Mellitus

2020 ◽  
Author(s):  
Peng Wang ◽  
Fei Chen ◽  
Xuedong Zhang
Keyword(s):  
Cyclosporine A ◽  
Inflammatory Diseases ◽  
Morphological Changes ◽  
Underlying Mechanism ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Diabetic Retina ◽  
Tnf Α ◽  
Type 2 Diabetic

Abstract Background:Cyclosporine-A has been regarded as an immunoregulatory and anti-inflammatory drug for the treatment of various immune inflammatory diseases. However, the effect of Cyclosporine-A on the retina of type 2 diabetic rats and the underlying mechanism remains to be elucidated. The objective of the present study was to investigate the effect and mechanism of Cyclosporine-A on diabetic retinopathy. Methods:Male Sprague-Dawley rats were established to type 2 diabetic model.After 6 weeks, diabetic rats and normal controls were intravitreally injected with Cs-A (42 ng/2 μL) to the left eye, and 2μL DMSO to the right eye for the control. Another part of normal wild-type rats was subjected to intravitreal injections into the left eyes with 5 μL PBS or HMGB-1 (5 ng/5 μL) or HMGB-1(5 ng/5 μL) plus Cs-A (42 ng/2 μL), respectively. Retinal morphological changes were observed with hematoxylin–eosin staining. Expressions of HMGB-1, IL-1β and TNF-α were detected by immunohistochemistry, ELISA or western blot. Results:Retinal expression levels of IL-1β and TNF-α were upregulated in type 2 diabetic rats and in normal rats with intravitreal injection of HMGB-1, which were attenuated by intravitreal Cs-A. Moreover, Cs-A decreased HMGB-1 expression in diabetic retina and relieved the retinopathy in type 2 diabetic rats. Conclusions:Intravitreal administration of Cs-A showed a protective effect on retina of diabetic rats, possibly by downregulating retinal expressions of IL-1β and TNF-α via the suppression of HMGB-1.

Effects of insulin on renal interstitial hydrostatic pressure and natriuretic response to volume expansion in diabetic rats

2004 ◽  
Vol 286 (4) ◽  
pp. R751-R755 ◽  
Author(s):  
Daiyi Tang ◽  
Tianzheng Yu ◽  
Ali A. Khraibi
Keyword(s):  
Hydrostatic Pressure ◽  
Volume Expansion ◽  
Insulin Treatment ◽  
Critical Role ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Control Group ◽  
Sprague Dawley ◽  
Water Excretion ◽  
Fractional Excretion Of Sodium

Diabetes mellitus (DM) is characterized by alterations in fluid balance and blood volume homeostasis. Renal interstitial hydrostatic pressure (RIHP) has been shown to play a critical role in mediating sodium and water excretion under various conditions. The objective of this study was to determine the effects of immediate and delayed initiation of insulin treatment on the restoration of the relationship between RIHP, natriuretic, and diuretic responses to acute saline volume expansion (VE) in diabetic rats. Diabetes was induced by an intraperitoneal injection of streptozotocin (STZ; 65 mg/kg body wt). Four groups of female Sprague-Dawley rats were studied: normal control group (C), untreated diabetic group (D), immediate insulin-treated diabetic group (DI; treatment with insulin for 2 wk was initiated immediately when diabetes was confirmed, which was 2 days after STZ injection), and delayed insulin-treated diabetic group (DDI; treatment with insulin for 2 wk was initiated 2 wk after STZ injection). RIHP and sodium and water excretions were measured before and during VE (5% body wt/30 min) in the four groups of anesthetized rats. VE significantly increased RIHP, fractional excretion of sodium (FENa), and urine flow rate (V) in all groups of rats. Basal RIHP, RIHP response to VE (ΔRIHP), and FENa and V responses to VE (ΔFENa and ΔV) were significantly lower in the D group compared with the C group of rats. ΔRIHP was significantly higher in both DI and DDI groups compared with D group but was similar to that of the C group of rats. While in the DI group the ΔFENa response to VE was restored, ΔFENa was significantly increased in DDI compared with D group, but it remained lower than that of the C group. In conclusion, insulin treatment initiated immediately after the onset of diabetes restores basal RIHP and RIHP, natriuretic, and diuretic responses to VE; however, delayed insulin treatment restores the basal RIHP and RIHP response to VE but does not fully restore the natriuretic response to VE.

scholarly journals Non-invasive investigation of early kidney damage in streptozotocin-induced diabetic rats by intravoxel incoherent motion diffusion-weighted (IVIM) MRI

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
You-Zhen Feng ◽  
Xiao-Qiao Chen ◽  
Zhong-Yuan Cheng ◽  
Qi-Ting Lin ◽  
Ping-Kang Chen ◽  
...  
Keyword(s):  
Urine Volume ◽  
Diabetic Rats ◽  
Intravoxel Incoherent Motion ◽  
Control Group ◽  
Sprague Dawley ◽  
Adc Value ◽  
Collagen Expression ◽  
Adc Values ◽  
D Values ◽  
Over Time

Abstract Background The current study investigated the performance of intravoxel incoherent motion diffusion (IVIM) technology in monitoring early renal injury in streptozotocin rats. Methods Forty-eight Sprague-Dawley (SD) rats were divided into a control group and a diabetic mellitus (DM) group. Six rats in each group were randomly selected for MR scans at four different time points (0, 4, 8, and 12 weeks). The IVIM-derived parameters (D, D*, f and ADC values) of the renal cortex (CO), outer and inner stripe of the outer medulla (OS, IS), and internal medulla (IM) were acquired. Changes in each IVIM-derived parameter over time were analyzed, and differences between the two groups at each point were assessed. The associations between the IVIM parameters and IV collagen expression, urine volume (UV), blood urea nitrogen (BUN), and serum creatinine (Scr) were investigated. Results The D and D* values of CO and the ADC values of CO, OS, IS and IM displayed significantly different trends between the two groups over time (P<0.05). In addition, significant correlations were discovered between the D* value of CO and UV and BUN (r=0.527, P=0.033; r=0.617, P=0.005), between the ADC value of IM and BUN (r=0.557, P=0.019) and between the f value of IM and BUN (r=0.527, P=0.033). No correlation was found between IVIM parameters and IV collagen expression and Scr. Conclusions IVIM is a potential sensitive and noninvasive technology for the simultaneous assessment of early renal cortical and medullary injuries induced by diabetes.

scholarly journals Cyclosporine-A Attenuates Retinal Inflammation by Inhibiting HMGB-1 Formation in Rats with Type 2 Diabetes Mellitus

2020 ◽  
Author(s):  
Peng Wang ◽  
Fei Chen ◽  
Xuedong Zhang
Keyword(s):  
Cyclosporine A ◽  
Inflammatory Diseases ◽  
Morphological Changes ◽  
Underlying Mechanism ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Diabetic Retina ◽  
Tnf Α ◽  
Type 2 Diabetic

Abstract Background:Cyclosporine-A has been regarded as an immunoregulatory and anti-inflammatory drug for the treatment of various immune inflammatory diseases. However, the effect of Cyclosporine-A on the retina of type 2 diabetic rats and the underlying mechanism remains to be elucidated. The objective of the present study was to investigate the effect and mechanism of Cyclosporine-A on diabetic retinopathy. Methods:Male Sprague-Dawley rats were established to type 2 diabetic model.After 6 weeks, diabetic rats and normal controls were intravitreally injected with Cs-A (42 ng/2 μL) to the left eye, and 2μL DMSO to the right eye for the control. Another part of normal wild-type rats was subjected to intravitreal injections into the left eyes with 5 μL PBS or HMGB-1 (5 ng/5 μL) or HMGB-1(5 ng/5 μL) plus Cs-A (42 ng/2 μL), respectively. Retinal morphological changes were observed with hematoxylin–eosin staining. Expressions of HMGB-1, IL-1β and TNF-α were detected by immunohistochemistry, ELISA or western blot. Results:Retinal expression levels of IL-1β and TNF-α were upregulated in type 2 diabetic rats and in normal rats with intravitreal injection of HMGB-1, which were attenuated by intravitreal Cs-A. Moreover, Cs-A decreased HMGB-1 expression in diabetic retina and relieved the retinopathy in type 2 diabetic rats. Conclusions:Intravitreal administration of Cs-A showed a protective effect on retina of diabetic rats, possibly by downregulating retinal expressions of IL-1β and TNF-α via the suppression of HMGB-1.

scholarly journals Cyclosporine-A Attenuates Retinal Inflammation by Inhibiting HMGB-1 Formation in Rats with Type 2 Diabetes Mellitus

2019 ◽  
Author(s):  
Peng Wang ◽  
Fei Chen ◽  
Xuedong Zhang
Keyword(s):  
Cyclosporine A ◽  
Inflammatory Diseases ◽  
Morphological Changes ◽  
Underlying Mechanism ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Diabetic Retina ◽  
Tnf Α ◽  
Type 2 Diabetic

Abstract Background:Cyclosporine-A has been regarded as an immunoregulatory and anti-inflammatory drug for the treatment of various immune inflammatory diseases. However, the effect of Cyclosporine-A on the retina of type 2 diabetic rats and the underlying mechanism remains to be elucidated. The objective of the present study was to investigate the effect and mechanism of Cyclosporine-A on diabetic retinopathy. Methods:Male Sprague-Dawley rats were established to type 2 diabetic model.After 6 weeks, diabetic rats and normal controls were intravitreally injected with Cs-A (42 ng/2 μL) to the left eye, and 2μL DMSO to the right eye for the control. Another part of normal wild-type rats was subjected to intravitreal injections into the left eyes with 5 μL PBS or HMGB-1 (5 ng/5 μL) or HMGB-1(5 ng/5 μL) plus Cs-A (42 ng/2 μL), respectively. Retinal morphological changes were observed with hematoxylin–eosin staining. Expressions of HMGB-1, IL-1β and TNF-α were detected by immunohistochemistry, ELISA or western blot. Results:Retinal expression levels of IL-1β and TNF-α were upregulated in type 2 diabetic rats and in normal rats with intravitreal injection of HMGB-1, which were attenuated by intravitreal Cs-A. Moreover, Cs-A decreased HMGB-1 expression in diabetic retina and relieved the retinopathy in type 2 diabetic rats. Conclusions:Intravitreal administration of Cs-A showed a protective effect on retina of diabetic rats, possibly by downregulating retinal expressions of IL-1β and TNF-α via the suppression of HMGB-1.

scholarly journals Protective Effect ofMomordica charantiaFruit Extract on Hyperglycaemia-Induced Cardiac Fibrosis

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Razif Abas ◽  
Faizah Othman ◽  
Zar Chi Thent
Keyword(s):  
Body Weight ◽  
Cardiac Fibrosis ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
The Body ◽  
Diabetic Group ◽  
Control Group ◽  
Sprague Dawley ◽  
Fruit Extract ◽  
Cardiac Tissues

In diabetes mellitus, cardiac fibrosis is characterized by increase in the deposition of collagen fibers. The present study aimed to observe the effect ofMomordica charantia(MC) fruit extract on hyperglycaemia-induced cardiac fibrosis. Diabetes was induced in the male Sprague-Dawley rats with a single intravenous injection of streptozotocin (STZ). Following 4 weeks of STZ induction, the rats were subdivided (n= 6) into control group (Ctrl), control group treated withMC(Ctrl-MC), diabetic untreated group (DM-Ctrl), diabetic group treated withMC(DM-MC), and diabetic group treated with 150 mg/kg of metformin (DM-Met). Administration ofMCfruit extract (1.5 g/kg body weight) in diabetic rats for 28 days showed significant increase in the body weight and decrease in the fasting blood glucose level. Significant increase in cardiac tissues superoxide dismutase (SOD), glutathione contents (GSH), and catalase (CAT) was observed followingMCtreatment. Hydroxyproline content was significantly reduced and associated morphological damages reverted to normal. The decreased expression of type III and type IV collagens was observed under immunohistochemical staining. It is concluded thatMCfruit extract possesses antihyperglycemic, antioxidative, and cardioprotective properties which may be beneficial in the treatment of diabetic cardiac fibrosis.

Effect of Ginkgo Biloba Extract on Contractility Enhancement of Diaphragm of Rats with Type 2 Diabetes

2014 ◽  
Vol 989-994 ◽  
pp. 1015-1019
Author(s):  
Xu Sheng Li ◽  
Ren Yan Wu ◽  
Ye Hu
Keyword(s):  
Type 2 Diabetes ◽  
Ginkgo Biloba ◽  
Ginkgo Biloba Extract ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Control Group ◽  
Metabolism Enzymes ◽  
Type 2 Diabetic

To investigate the effects of Ginkgo biloba extract (GbE) on the activities of energy metabolism enzymes and contraction capacity of diaphragm from type 2 diabetic rats. Forty SD mile rats were randomly divided into normal control group (n=10) and model group (n=30). Type 2 diabetes models were induced by feeding with high-sucrose-high-fat diet and intraperitoneal injecting 25mg/kg streptozotocin. 20 successful models were rearranged to two groups: diabetic group and GbE treatment group, 10 rats in each. Then the saline and 8mg·kg-1·d-1 of GbE were respectively intraperitoneal injected, once a day continuously for 8 weeks. Then diaphragm contractility was assessed using Peak twitch tension (Pt), Maximum tetanic tension (P0) and fatigue index (FI) in vitro diaphragm strip preparations. Cytochrome oxidase (CCO), lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) in diaphragm were detected and the varieties of diaphragm ultrastructure were observed. Compared with control group, Pt, P0 and FI in diabetic group decreased significantly (P < 0.01); the activity of CCO, LDH and SDH in the tissues was obviously reduced than those in control group (P < 0.01). The ultrastructure in diabetic group under electron microscope indicated that diaphragm mitochondrions swelled and degenerated. The above changes were inhibited by GbE. GbE can enhance contraction capacity of diaphragm from type 2 diabetic rats by increasing the aerobic oxidation capacity, glycolytic capacity and the function of respiratory chain.

scholarly journals Swimming training and Plantago psyllium ameliorate cognitive impairment and glucose tolerance in streptozotocin–nicotinamide-induced type 2 diabetic rats

2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Hesam Parsa ◽  
Zahra Moradi-Khaligh ◽  
Sara Rajabi ◽  
Kamal Ranjbar ◽  
Alireza Komaki
Keyword(s):  
Food Intake ◽  
Glucose Tolerance ◽  
Lipid Profile ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Control Group ◽  
Swimming Training ◽  
Plantago Psyllium ◽  
Type 2 Diabetic

AbstractBrain malfunction is common in diabetic patients. On the other hand, a growing body of research points to the beneficial effect of medicinal plants and exercise training on insulin sensitivity and brain function. Therefore, the aim of the present study was to investigate the effect of co-administration of swimming training and Plantago psyllium (mixed with standard pelleted food at a weight ratio of 5%) on learning and memory impairment and glucose tolerance in type 2 diabetic rats. For this purpose, 10 healthy and 40 rats with type 2 diabetes were randomly allocated to five groups: healthy sedentary control group (Con), sedentary diabetic group (D), diabetic group subjected to swimming training (D + Tr), diabetic group receiving P. psyllium (D + Ps), and diabetic group subjected to swimming training and receiving P. psyllium (D + Ps + Tr). Diabetes was induced by a single intraperitoneal injection of nicotinamide (120 mg/kg) and streptozotocin (65 mg/kg) separately with 15 min intervals. Experimental groups were treated with swimming training and P. psyllium independently and simultaneously for 12 weeks. Lipid profile and food intake were measured and also, glucose tolerance was evaluated by glucose area under the curve (AUCg) using an oral glucose tolerance test. Passive avoidance learning (PAL) and memory were evaluated by shuttle box test and cognitive memory was assessed by novel object recognition (NOR) and elevated plus-maze (EPM) tests. Diabetic rats exhibited a significant increase in food intake, lipid profile, and AUCg compared to healthy rats. Step-through latency in the PAL acquisition trial (STL-a) and retention test (STL-r) were significantly lower in diabetic rats than in the control group. In the diabetic group without treatment, time spent in the dark compartment increased compared to the control group in the shuttle box test. Discrimination index and distance traveled reduced in diabetic rats. On the other hand, swimming training and P. psyllium alleviated food intake, lipid profile, and glucose tolerance in diabetic rats. Also, the STL-a, STL-r, discrimination index, and distance travelled in the D + Ps + Tr group were significantly more than the diabetic group. Results showed that 12 weeks of swimming training and receiving P. psyllium improved memory deficit in streptozotocin–nicotinamide-induced type 2 diabetic rats possibly through hypolipidemic and hypoglycemic effects. These results suggest that the administration of swimming training and P. psyllium simultaneously might be an effective intervention for the treatment of diabetes-induced behavioral deficits.

scholarly journals Effect of the Sodium-Glucose Cotransporter 2 Inhibitor, Dapagliflozin, on Genitourinary Infection in an Animal Model of Type 2 Diabetes

2020 ◽  
Vol 24 (1) ◽  
pp. 21-28
Author(s):  
Jin Bong Choi ◽  
Je Mo Yoo ◽  
Ye-Jee Lee ◽  
Jae Woong Kim ◽  
Seung-Ju Lee ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Urine Volume ◽  
Diabetic Rats ◽  
Control Group ◽  
Urine Glucose ◽  
Cytokine Analysis ◽  
Sodium Glucose Cotransporter ◽  
Long Evans ◽  
Genitourinary Infection

Purpose: To investigate the effect of dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, on inflammatory cytokines of urogenital tissue in a rat model of type 2 diabetes (T2DM) to infer pharmaceutical influence of dapagliflozin on genitourinary infection or inflammation.Methods: Study animals were divided into the following 4 groups of 10 animals each: (1) the Otsuka Long-Evans Tokushima Fatty (OLETF)-DA group treated with dapagliflozin at 1.0 mg/kg/day, (2) the OLETF-VO group treated with voglibose at 0.6 mg/kg/day, (3) the control group (OLETF-CO) given water, and (4) the Long-Evans Tokushima Otsuka (LETO) rats were included as nondiabetic control group. Changes in blood glucose, 24-hour urine volume, and urine glucose were measured. The interleukin-1β (IL-1β) and interleukin-18 (IL-18) levels in the bladder and the urethra were quantified, respectively.Results: The urine glucose level and the 24-hour urine volume at 12 weeks of treatment were significantly higher in the OLETF-DA group than that in any other group (P<0.05). The cytokine analysis of the bladder and urethra showed higher IL18 and IL-1β in the OLETF-DA and the OLETF-CO groups than that in the OLETF-VO and LETO groups (P<0.05). The cytokine levels did not differ between the OLETF-DA and the OLETF-CO groups, and the level of IL-18 in the OLETF-DA group was higher in the urethra than in the bladder.Conclusions: This study revealed that dapagliflozin increased the urine glucose concentration, resulting in an inflammatory response remain in the urogenital tract as the untreated diabetic rats. Therefore, when treating patients with T2DM with dapagliflozin, careful attention should be paid to genitourinary infection or inflammation.

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