scholarly journals Evaluation of the Central Effects of Systemic Lentiviral-Mediated Leptin Delivery in Streptozotocin-Induced Diabetic Rats

2021 ◽  
Vol 22 (24) ◽  
pp. 13197
Author(s):  
Kimberly A. Clark ◽  
Andrew C. Shin ◽  
Madhu P. Sirivelu ◽  
Ramya C. MohanKumar ◽  
Sreenivasa R. Maddineni ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Fluorescent Protein ◽  
Lentiviral Vector ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Sprague Dawley Rats ◽  
Green Fluorescent

Type 1 diabetes (T1D) is characterized by hyperphagia, hyperglycemia and activation of the hypothalamic–pituitary–adrenal (HPA) axis. We have reported previously that daily leptin injections help to alleviate these symptoms. Therefore, we hypothesized that leptin gene therapy could help to normalize the neuroendocrine dysfunction seen in T1D. Adult male Sprague Dawley rats were injected i.v. with a lentiviral vector containing the leptin gene or green fluorescent protein. Ten days later, they were injected with the vehicle or streptozotocin (STZ). HPA function was assessed by measuring norepinephrine (NE) levels in the paraventricular nucleus (PVN) and serum corticosterone (CS). Treatment with the leptin lentiviral vector (Lepvv) increased leptin and insulin levels in non-diabetic rats, but not in diabetic animals. There was a significant reduction in blood glucose levels in diabetic rats due to Lepvv treatment. Both NE levels in the PVN and serum CS were reduced in diabetic rats treated with Lepvv. Results from this study provide evidence that leptin gene therapy in STZ-induced diabetic rats was able to partially normalize some of the neuroendocrine abnormalities, but studies with higher doses of the Lepvv are needed to develop this into a viable option for treating T1D.

scholarly journals Anti-diabetic effects of aqueous extract of Dendropanax morbifera Lev. leaves in streptozotocin-induced diabetic Sprague-Dawley rats

2021 ◽  
Vol 61 (4) ◽  
pp. e38
Author(s):  
Min-Jae Kim ◽  
Ye-Jin Kang ◽  
Dong-Eon Lee ◽  
Suk Kim ◽  
Se-Hun Lim ◽  
...  
Keyword(s):  
Diabetic Control ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Glucose Levels ◽  
Blood Biochemical ◽  
Blood Glucose Levels ◽  
Sd Rats ◽  
Sprague Dawley Rats ◽  
Dendropanax Morbifera ◽  
Treatment Of Diabetes

This study examined the anti-diabetic effects of aqueous extracts of Dendropanax morbifera leaves (DMWEs) in streptozotocin-induced diabetic Sprague-Dawley (SD) rats. Thirty male SD rats (body weight [BW], 250.4 ± 19.7 g) were divided into the following six groups: normal control rats (NC), diabetic control rats (DC), diabetic rats treated with metformin HCl 100 mg/kg BW (DT), diabetic rats treated with DMWEs 50 mg/kg BW (DM-50), diabetic rats treated with DMWEs 100 mg/kg BW (DM-100), and diabetic rats treated with DMWEs 200 mg/kg BW (DM-200). From two weeks of administration of DMWEs, the BW of all groups treated with DMWEs increased significantly compared to DC (p < 0.05). At four weeks after treatment, the blood glucose levels in DT, DM-100, and DM-200 decreased below 200 mg/dL, while the glycated hemoglobin concentrations in all groups administered DMWEs were similar to those of NC and DT. Regarding the blood biochemical parameters, the levels of aspartate transaminase, alanine transaminase, blood urea nitrogen, and creatinine in DM-100 and DM-200 were similar to those in NC and DT. Overall, these results highlight the effectiveness of DM-100 in the treatment of diabetes.

Reduced renal responses to volume expansion in streptozotocin-induced diabetic rats

1989 ◽  
Vol 257 (3) ◽  
pp. R672-R679 ◽  
Author(s):  
K. P. Patel ◽  
P. L. Zhang
Keyword(s):  
Volume Expansion ◽  
Diabetic Rats ◽  
Control Group ◽  
Sprague Dawley ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Sprague Dawley Rats ◽  
Before And After ◽  
Abnormal Volume ◽  
Group A

To determine whether the volume reflex is defective in the diabetic state, the diuretic and natriuretic responses to acute volume expansion (VE) were measured in streptozotocin (STZ)-induced diabetic (Dia) rats. Urine flow (UV) and sodium excretion (UNaV) were measured before and after VE from innervated and denervated kidneys in anesthetized (Inactin 0.1 g/kg, ip) control and Dia rats (Sprague-Dawley rats injected with vehicle or STZ 65 mg/kg ip, respectively, 2 wk before the experiment). Blood glucose levels were significantly elevated in the Dia group compared with the control group. A VE of 1.2 ml/min for 15 min produced a significantly greater diuresis and natriuresis in control rats compared with Dia rats. In addition, reducing the hyperglycemia in Dia rats (third group) by treatment with insulin reversed the blunted UV and UNaV responses to VE. Ratios of UV (innervated-denervated, I/D) before and after VE indicate significant increases in UV by the innervated kidneys, relative to the denervated kidneys in all three groups. I/D ratios of UNa V were not different between the three groups before VE, but were significantly smaller in the Dia rats compared with both control and STZ plus insulin groups after VE. This study demonstrates that 1) there is an abnormal volume reflex in the STZ-induced Dia rats; 2) the natriuresis due to renal sympatho-inhibition is blunted in response to VE in Dia rats; and 3) restoring the glucose levels to normal by insulin treatment in the Dia rats normalizes the volume reflex.

NEUROPROTECTIVE POTENTIAL OF AZADIRACHTA INDICA LEAVES IN DIABETIC RATS

2017 ◽  
Vol 10 (4) ◽  
pp. 243
Author(s):  
Nidhi Srivastva ◽  
Naveen Kumar Gupta ◽  
Sanjeev Puri ◽  
Veena Puri
Keyword(s):  
Blood Glucose ◽  
Azadirachta Indica ◽  
Leaf Extract ◽  
Microscopic Analysis ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Sprague Dawley Rats ◽  
Neuro Protection

Objective: Azadirachta indica is a treasure of multiple pharmacological properties and presently leaves of this plant have been explored to evaluate the neuroprotective potential in diabetic rats.Methods: Male Sprague-Dawley rats were injected with single intra peritoneal dose of streptozotocin (60mg/ Kg body weight (BW.) to develop animal model of diabetes. Post twenty one days of streptozotocin induction, animals were treated with aqueous Azadirachta indica Leaf Extract (ALE, 600mg/Kg BW.) for seven consecutive days. Followed this, all animals were evaluated for the levels of blood glucose, lipid peroxidation (LPO), C Reactive Proteins (CRP), pro oxidant biomarkers and histological changes.Results: Streptozotocin treated rats exhibited elevated levels of blood glucose, LPO, CRP and altered pro oxidant biomarkers in comparison to control rats. Additionally, histological alterations/damage was evidenced as fragmentation, vacuolization, inflammation etc. However, ALE treatment to these rats significantly decreased blood glucose levels, LPO, CRP levels and restored pro-oxidants status. Light microscopic and ultra microscopic analysis also indicated less damage, tissue architectural changes in comparison to untreated diabetic rats. Further decrease in hyperalgesia and inflammation levels; along with protective and restorative changes following ALE treatment suggested the neuroprotective potential of Azadirachta indica leaves in diabetic rats.Conclusion: The oral administration of ALE to streptozotocin induced diabetic animals resulted in neuro-protection against degenerative oxidative stress associated with metabolic and histopathological damage in the brain.Key words:  Azadirachta indica, Antioxidants, Hyperalgesia, Neuroprotection  

scholarly journals Antihyperglycemic Activity of Java Tea-Based Functional Drink-Loaded Chitosan Nanoparticle in Streptozotocin-Induced Diabetic Rats

2021 ◽  
Vol 28 (3) ◽  
pp. 212
Author(s):  
Monita Rekasih ◽  
Tjahja Muhandri ◽  
Mega Safithri ◽  
Christofora Hanny Wijaya
Keyword(s):  
Blood Glucose ◽  
Bioactive Compounds ◽  
Diabetic Rats ◽  
Total Phenolic ◽  
Sprague Dawley ◽  
Antihyperglycemic Activity ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Sprague Dawley Rats ◽  
Functional Drink

Functional drinks containing the leaves of Java tea has been shown to offer many health functionalities, particularly to lower blood glucose levels, due to its bioactive compounds. Nanoencapsulation technology was reported being able to protect these bioactive compounds and also enhance their bioavailability. This study examined the use of nanoencapsulation techniques to improve the bioavailability of Java tea-based functional effervescent drink and enhance its antihyperglycemic activity. Three versions were prepared in this study: ready to drink (RTD) as the control, microencapsulated, and nanoencapsulated. They were all measured for their total phenolic content (TPC) before being tested for their antihyperglycemic activity. The TPC of RTD, microencapsulated, and nanoencapsulated Java tea-based functional drinks (JTFD) were 998,425, 735,433, and 663,517 ppm, respectively. The antihyperglycemic activities were evaluated by feeding each beverage to streptozotocin-induced diabetic Sprague Dawley rats for fourteen days. Nanoencapsulated JTFD was found to be more superior than the other two formulations to decrease the blood glucose level (7.98%), maintain the feed intake, body weight, improve the viability of Langerhans and beta-cells by 49.09%, 32.50%, respectively.

Abstract 3880: GRK2 Inhibition Prevents Development Of Cardiac Insulin Resistance And Impaired Glucose Uptake In Post Ischemic Heart Failure

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Michele Ciccarelli ◽  
Giuseppe Rengo ◽  
Kurt Chuprun ◽  
Gaetano Santulli ◽  
Bruno Trimarco ◽  
...  
Keyword(s):  
Heart Failure ◽  
Glucose Uptake ◽  
Fluorescent Protein ◽  
Sprague Dawley ◽  
Myocardial Glucose Uptake ◽  
Akt Phosphorylation ◽  
Neonatal Cardiomyocytes ◽  
Sprague Dawley Rats ◽  
Green Fluorescent ◽  
And Function

The beta adrenergic receptor (βAR) kinase, GRK2, is upregulated and participates to the evolution of heart failure (HF) through downregulation and desensitization of βARs. Recent studies showed that this molecule affects insulin signaling and reduce glucose uptake in hepatocytes and adipocytes. We hypothesized that in HF, GRK2 reduces cardiac performance also through inhibition of cardiac glucose metabolism. In 12 week old Sprague/Dawley rats, we measured cardiac glucose uptake by PET 3 days, 3 and 6 weeks after myocardial infarction (MI). Function and cardiac dimensions were measured by echocardiography. We observed that glucose uptake was reduced in animal post-MI at 3 and 6 weeks respect to healthy animals (3 rd week: 1.3±0.22 vs 2.1±0.3; 6 th week: 1±0.1 vs 2.4±0.2, ml/min/g, p<0.05). No difference was observed in glucose uptake acutely after surgery. Echo showed cardiac dilation and reduced function at 6 weeks (LVD: 9.2± 0.3 vs 7.2± 0.4 mm; EF: 42%±1.1 vs 66%±2.2, p<0.05, Sham vs MI). To inhibit GRK2 in the heart during post-ischemic HF, we delivered the GRK2 inhibitor βARKct by adeno-associated type 6 virus (AAV6) to the left ventricle before induction of the MI. As a control we treated rats with AAV6 encoding for the green fluorescent protein (GFP). Cardiac dilation and function were preserved after 6 weeks post MI in AAV6 βARKct respect to AAV6GFP rats (LVD: 7.73 ±0.25 vs 9.9 ±0.8 mm; EF: 55%±2.25 vs 44%±2, p<0.05). Glucose uptake was better preserved in AAV6βARKct rats after 3 and 6 weeks post MI respect to AAV6GFP group (3rd week: 2.3±0.3 vs 1.2±0.2; 6th week: 1.8±0.2 vs 1.1±0.05, ml/min/g, p<0.05). Since Akt mediates most of the anabolic effects of insulin in cells, we evaluated the effects of GRK2 overexpression by adenovirus (ADGRK2) in neonatal cardiomyocytes (NRVMs) on Akt phosphorylation later on insulin stimulation (ins, 10 – 6 M). As control we induced overexpression of GFP by adenovirus (ADGFP). We observed reduced activation of Akt in presence of GRK2 overexpression as compared to the ADGFP treated cells (1.2±0.2- vs. 3.5±0.4- fold activation over basal, p<0.05). Our data show that post MI, impaired glucose extraction precedes development of HF, and that early GRK2 inhibition prevents impaired myocardial glucose uptake and HF development.

134 The Effect of Adipose Derived Stromal Vascular Fraction on Stasis Zone in an Experimental Burn Model on Streptozocin – Induced Diabetic Rats

2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S89-S90
Author(s):  
Cagri A Uysal ◽  
Burak Ozkan ◽  
Abbas Najimaldin Muhsun Al Bayati ◽  
Gonca Ozgun ◽  
Kadri Akinci ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Cell Density ◽  
Inflammatory Cell ◽  
Burn Injury ◽  
Stromal Vascular Fraction ◽  
Vascular Density ◽  
Sprague Dawley ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Sprague Dawley Rats

Abstract Introduction Stasis zone is the encircling area of the coagulation zone which is a critical area determining the depth and width of the necrosis in burn patients. In our study we aim to salvage the stasis zone by injecting adipose derived stromal vascular fraction (ADSVF). Methods Intraperitoneal Streptozotocin was administered for the induction of diabetes mellitus (DM) and the development of DM was confirmed by the measurement of blood glucose levels in the blood samples with blood glucometer weekly 48 hours after injection. Rats with blood glucose levels above 200 mg/dl were accepted as diabetic. The diabetic animals were followed for 4 weeks before the intervention. Thermal injury was applied on dorsum of diabetic Sprague – Dawley rats (n=20) according to the previously described ‘‘comb burn’’ model. After the burn injury (30 minutes) on Sprague - Dawley rats; rat dorsum was separated into 2 equal parts consisting of 4 burn zones (3 stasis zone) on each pair. ADSVF cells harvested from inguinal fat pads of diabetic Sprague - Dawley rats (n=5) were injected on the right side while same amount of phosphate buffered saline (PBS) injected on the left side of the same animal. One week later, average vital tissue on the statis zone was determined by macroscopy, angiography and microscopy. Vascular density, inflammatory cell density and gradient of fibrosis were determined via immunohistochemical assay. Results Macroscopic stasis zone tissue survivability percentage (32 ± 3.28 %, 57 ± 4.28 %), average number of vessels (10.28 ± 1.28, 19.43 ± 1.72), capillary count (15.67 ± 1.97, 25.35 ± 2.15) and vascular density (1.55 ± 0.38, 2.14 ± 0.45) were higher on ADSVF side. Fibrosis gradient (1.87 ± 0.51, 1.50 ± 0.43) and inflammatory cell density (1.33 ± 0.40, 1.20 ± 0.32) were higher on the PBS side. Conclusions Macroscopic and microscopic findings determined that ADSVF has a statistically significant benefit for salvaging stasis zone on acute burn injuries in DM.

Juxtamedullary microvascular dysfunction during the hyperfiltration stage of diabetes mellitus

1994 ◽  
Vol 267 (1) ◽  
pp. F99-F105 ◽  
Author(s):  
K. Ohishi ◽  
M. I. Okwueze ◽  
R. C. Vari ◽  
P. K. Carmines
Keyword(s):  
Diabetes Mellitus ◽  
Microvascular Dysfunction ◽  
Sprague Dawley ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Sprague Dawley Rats ◽  
Vasoconstrictor Response ◽  
Wide Range ◽  
Single Nephron

This study was designed to identify and localize defects in renal microvascular function during the hyperfiltration stage of diabetes mellitus. Male Sprague-Dawley rats were injected intravenously with 65 mg/kg streptozotocin (IDDM rats) or vehicle (sham rats). IDDM rats received insulin (3 U.kg-1.day-1) via an osmotic minipump; sham rats received diluent. During the ensuing 2-wk period, blood glucose levels averaged 89 +/- 2 mg/dl in 33 sham rats and 290 +/- 13 mg/dl in 37 IDDM rats. At the end of this period, inulin clearance was elevated in eight IDDM rats (1.43 +/- 0.17 ml.min-1.g kidney wt-1) compared with six sham rats (0.78 +/- 0.05 ml.min-1.g kidney wt-1). The remaining animals served as tissue donors for study of the renal microvasculature using the in vitro blood-perfused juxtamedullary nephron technique. Kidneys from sham and IDDM rats were perfused with homologous blood at a renal arterial pressure of 110 mmHg. Juxtamedullary single-nephron glomerular filtration rate was higher in IDDM rats (41.5 +/- 5.4 nl/min) than in sham rats (25.4 +/- 2.4 nl/min). Afferent arteriolar inside diameter was greater in IDDM rats (34 +/- 2 microns) than in sham rats (22 +/- 1 microns); however, efferent arteriolar diameter did not differ between groups. The afferent arteriolar vasoconstrictor response to norepinephrine (NE) was attenuated in IDDM rats, relative to sham rats, over a wide range of NE concentrations. In contrast, NE evoked similar degrees of efferent vasoconstriction in IDDM and sham rats.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Influence of GABA and GABA-producing Lactobacillus brevis DPC 6108 on the development of diabetes in a streptozotocin rat model

2016 ◽  
Vol 7 (3) ◽  
pp. 409-420 ◽  
Author(s):  
T.M. Marques ◽  
E. Patterson ◽  
R. Wall ◽  
O. O’Sullivan ◽  
G.F. Fitzgerald ◽  
...  
Keyword(s):  
Body Weight ◽  
Serum Insulin ◽  
Lactobacillus Brevis ◽  
Diabetic Rats ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Metabolic Markers ◽  
Glucose Levels ◽  
Intestinal Length ◽  
Sprague Dawley Rats

The aim of this study was to investigate if dietary administration of γ-aminobutyric acid (GABA)-producing Lactobacillus brevis DPC 6108 and pure GABA exert protective effects against the development of diabetes in streptozotocin (STZ)-induced diabetic Sprague Dawley rats. In a first experiment, healthy rats were divided in 3 groups (n=10/group) receiving placebo, 2.6 mg/kg body weight (bw) pure GABA or L. brevis DPC 6108 (~109microorganisms). In a second experiment, rats (n=15/group) were randomised to five groups and four of these received an injection of STZ to induce type 1 diabetes. Diabetic and non-diabetic controls received placebo [4% (w/v) yeast extract in dH2O], while the other three diabetic groups received one of the following dietary supplements: 2.6 mg/kg bw GABA (low GABA), 200 mg/kg bw GABA (high GABA) or ~109 L. brevis DPC 6108. L. brevis DPC 6108 supplementation was associated with increased serum insulin levels (P<0.05), but did not alter other metabolic markers in healthy rats. Diabetes induced by STZ injection decreased body weight (P<0.05), increased intestinal length (P<0.05) and stimulated water and food intake. Insulin was decreased (P<0.05), whereas glucose was increased (P<0.001) in all diabetic groups, compared with non-diabetic controls. A decrease (P<0.01) in glucose levels was observed in diabetic rats receiving L. brevis DPC 6108, compared with diabetic-controls. Both the composition and diversity of the intestinal microbiota were affected by diabetes. Microbial diversity in diabetic rats supplemented with low GABA was not reduced (P>0.05), compared with non-diabetic controls while all other diabetic groups displayed reduced diversity (P<0.05). L. brevis DPC 6108 attenuated hyperglycaemia induced by diabetes but additional studies are needed to understand the mechanisms involved in this reduction.

scholarly journals Antecedent glycemic control reduces severe hypoglycemia-induced neuronal damage in diabetic rats

2013 ◽  
Vol 304 (12) ◽  
pp. E1331-E1337 ◽  
Author(s):  
Candace M. Reno ◽  
Tariq Tanoli ◽  
Adam Bree ◽  
Dorit Daphna-Iken ◽  
Chen Cui ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Brain Damage ◽  
Insulin Treatment ◽  
Neuronal Damage ◽  
Blood Glucose Control ◽  
Severe Hypoglycemia ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Glucose Levels ◽  
Sprague Dawley Rats

Brain damage due to severe hypoglycemia occurs in insulin-treated people with diabetes. This study tests the hypothesis that chronic insulin therapy that normalizes elevated blood glucose in diabetic rats would be neuroprotective against brain damage induced by an acute episode of severe hypoglycemia. Male Sprague-Dawley rats were split into three groups: 1) control, non-diabetic; 2) STZ-diabetic; and 3) insulin-treated STZ-diabetic. After 3 wk of chronic treatment, unrestrained awake rats underwent acute hyperinsulinemic severe hypoglycemic (10–15 mg/dl) clamps for 1 h. Rats were subsequently analyzed for brain damage and cognitive function. Severe hypoglycemia induced 15-fold more neuronal damage in STZ-diabetic rats compared with nondiabetic rats. Chronic insulin treatment of diabetic rats, which nearly normalized glucose levels, markedly reduced neuronal damage induced by severe hypoglycemia. Fortunately, no cognitive defects associated with the hypoglycemia-induced brain damage were observed in any group. In conclusion, antecedent blood glucose control represents a major modifiable therapeutic intervention that can afford diabetic subjects neuroprotection against severe hypoglycemia-induced brain damage.

scholarly journals Nicotine Exposure Exacerbates Development of Cataracts in a Type 1 Diabetic Rat Model

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Nima Tirgan ◽  
Gabriela A. Kulp ◽  
Praveena Gupta ◽  
Adam Boretsky ◽  
Tomasz A. Wiraszka ◽  
...  
Keyword(s):  
Rat Model ◽  
Serum Levels ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Positive Trend ◽  
Sprague Dawley ◽  
Nicotine Treatment ◽  
Sprague Dawley Rats ◽  
Diabetic Rat Model

Diabetes and smoking are known risk factors for cataract development. In this study, we evaluated the effect of nicotine on the progression of cataracts in a type 1 diabetic rat model. Diabetes was induced in Sprague-Dawley rats by a single injection of 65 mg/kg streptozotocin. Daily nicotine injections were administered subcutaneously. Forty-five rats were divided into groups of diabetics with and without nicotine treatment and controls with and without nicotine treatment. Progression of lens opacity was monitored using a slit lamp biomicroscope and scores were assigned. To assess whether systemic inflammation played a role in mediating cataractogenesis, we studied serum levels of eotaxin, IL-6, and IL-4. The levels of the measured cytokines increased significantly in nicotine-treated and untreated diabetic animals versus controls and demonstrated a positive trend in the nicotine-treated diabetic rats. Our data suggest the presence of a synergistic relationship between nicotine and diabetes that accelerated cataract formation via inflammatory mediators.

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