Abstract P312: A Novel Selective Melanocortin-4 Receptor Agonist Attenuates Bradycardia and Hyperglycemia in Diabetic Rats

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Jussara M do Carmo ◽  
Alexandre A da Silva ◽  
John E Hall
Keyword(s):  
Blood Glucose ◽  
Food Intake ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Glucose Levels ◽  
Melanocortin 4 Receptor ◽  
Sprague Dawley Rats ◽  
New Strategy ◽  
Chronic Infusion ◽  
Treatment Of Diabetes

We previously demonstrated that functional brain melanocortin 3/4 receptors (MC3/4R) are required for leptin to exert its chronic cardiovascular and antidiabetic actions. To determine if chronic treatment with a selective MC4R agonist reduces blood glucose and prevents bradycardia in diabetic rats, we used a novel compound with high affinity to MC4R. Male 12-week-old Sprague-Dawley rats (n=5/group) were instrumented with telemetry probes for determination of mean arterial pressure (MAP) and heart rate (HR) 24-hrs/day and an intracerebroventricular (ICV) cannula was placed in the brain lateral ventricle for continuous infusion of the selective MC4R agonist PL6214 (2.5 μg/hr) or MTII (a non-selective MC3/4R agonist, 10 ng/hr) via osmotic minipump. Induction of diabetes caused hyperphagia (20±1 to 32±2 g), hyperglycemia (89±3 to 494±44 mg/dl) and bradycardia (-47 bpm). Chronic infusion of PL6214 for 11 days transiently reduced food intake which returned to diabetic values by day 6 after starting the infusions, whereas chronic infusion of MTII caused a reduction in food intake lasting only 3-4 days. PL6214 reduced blood glucose by 63% on day 2 and 16% by day 11 of infusion, and prevented further bradycardia induced by diabetes (-35±14 bpm on the last day of infusion). Chronic MTII infusion reduced blood glucose by 31% on day 2 and by day 6 glucose levels had already returned to values observed before treatment was started. MTII infusion did not attenuate the bradycardia (-99±13 bpm on the last day of infusion). Diabetes did not alter MAP, while the MC4R agonist increased MAP by 5±1 mmHg compared to control values. These results indicate that selective activation of MC4R agonist attenuates bradycardia and hyperglycemia in type 1 diabetes, and may provide a new strategy for treatment of diabetes. (P20GM104357, NHLBI-PO1HL51971, AHA-SDG5680016 and Palatin Technologies).

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 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.

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.

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.

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 Chronic central leptin infusion restores cardiac sympathetic-vagal balance and baroreflex sensitivity in diabetic rats

2008 ◽  
Vol 295 (5) ◽  
pp. H1974-H1981 ◽  
Author(s):  
Jussara M. do Carmo ◽  
John E. Hall ◽  
Alexandre A. da Silva
Keyword(s):  
Blood Pressure ◽  
Nervous System ◽  
Baroreflex Sensitivity ◽  
Control Period ◽  
Diabetic Rats ◽  
System Control ◽  
Sprague Dawley ◽  
Glucose Levels ◽  
Sprague Dawley Rats ◽  
Control Diabetes

This study tested whether leptin restores sympathetic-vagal balance, heart rate (HR) variability, and cardiac baroreflex sensitivity (BRS) in streptozotocin (STZ)-induced diabetes. Sprague-Dawley rats were instrumented with arterial and venous catheters, and a cannula was placed in the lateral ventricle for intracerebroventricular (ICV) leptin infusion. Blood pressure (BP) and HR were monitored by telemetry. BRS and HR variability were estimated by linear regression between HR and BP responses to phenylephrine or sodium nitroprusside and autoregressive spectral analysis. Measurements were made during control period, 7 days after induction of diabetes, and 7 days after ICV leptin infusion. STZ diabetes was associated with hyperglycemia (422 ± 17 mg/dl) and bradycardia (−79 ± 4 beats/min). Leptin decreased glucose levels (165 ± 16 mg/dl) and raised HR to control values (303 ± 10 to 389 ± 10 beats/min). Intrinsic HR (IHR) and chronotropic responses to a full-blocking dose of propranolol and atropine were reduced during diabetes (260 ± 7 vs. 316 ± 6, −19 ± 2 vs. −43 ± 6, and 39 ± 3 vs. 68 ± 8 beats/min), and leptin treatment restored these variables to normal (300 ± 7, −68 ± 10, and 71 ± 8 beats/min). Leptin normalized BRS (bradycardia, −2.6 ± 0.3, −1.7 ± 0.2, and −3.0 ± 0.5; and tachycardia, −3.2 ± 0.4, −1.9 ± 0.3, and −3.4 ± 0.3 beats·min−1·mmHg−1 for control, diabetes, and leptin) and HR variability (23 ± 4 to 11 ± 1.5 ms2). Chronic glucose infusion to maintain hyperglycemia during leptin infusion did not alter the effect of leptin on IHR but abolished the improved BRS. These results show rapid impairment of autonomic nervous system control of HR after the induction of diabetes and that central nervous system actions of leptin can abolish the hyperglycemia as well as the altered IHR and BRS in STZ-induced diabetes.

scholarly journals Effect of the Combination of Gelam Honey and Ginger on Oxidative Stress and Metabolic Profile in Streptozotocin-Induced Diabetic Sprague-Dawley Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Nur Fathiah Abdul Sani ◽  
Levin Kesu Belani ◽  
Chong Pui Sin ◽  
Siti Nor Amilah Abdul Rahman ◽  
Srijit Das ◽  
...  
Keyword(s):  
Body Weight ◽  
Metabolic Profile ◽  
Diabetic Control ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Glucose Levels ◽  
Sprague Dawley Rats ◽  
Gelam Honey ◽  
Antidiabetic Effects

Diabetic complications occur as a result of increased reactive oxygen species (ROS) due to long term hyperglycaemia. Honey and ginger have been shown to exhibit antioxidant activity which can scavenge ROS. The main aim of this study was to evaluate the antioxidant and antidiabetic effects of gelam honey, ginger, and their combination. Sprague-Dawley rats were divided into 2 major groups which consisted of diabetic and nondiabetic rats. Diabetes was induced with streptozotocin intramuscularly (55 mg/kg body weight). Each group was further divided into 4 smaller groups according to the supplements administered: distilled water, honey (2 g/kg body weight), ginger (60 mg/kg body weight), and honey + ginger. Body weight and glucose levels were recorded weekly, while blood from the orbital sinus was obtained after 3 weeks of supplementation for the estimation of metabolic profile: glucose, triglyceride (TG), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH): oxidized glutathione (GSSG), and malondialdehyde (MDA). The combination of gelam honey and ginger did not show hypoglycaemic potential; however, the combination treatment reduced significantly (P<0.05) SOD and CAT activities as well as MDA level, while GSH level and GSH/GSSG ratio were significantly elevated (P<0.05) in STZ-induced diabetic rats compared to diabetic control rats.

scholarly journals Studies on the Antidiabetic Activities ofCordyceps militarisExtract in Diet-Streptozotocin-Induced Diabetic Sprague-Dawley Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Yuan Dong ◽  
Tianjiao Jing ◽  
Qingfan Meng ◽  
Chungang Liu ◽  
Shuang Hu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Blood Glucose ◽  
Water Extract ◽  
Diabetic Rats ◽  
Cordyceps Militaris ◽  
Sprague Dawley ◽  
Alcohol Extract ◽  
Glucose Levels ◽  
Liver And Kidney ◽  
Antioxidative Effects

Due to substantial morbidity and high complications, diabetes mellitus is considered as the third “killer” in the world. A search for alternative antidiabetic drugs from herbs or fungi is highly demanded. Our present study aims to investigate the antidiabetic activities ofCordyceps militarison diet-streptozotocin-induced type 2 diabetes mellitus in rats. Diabetic rats were orally administered with water extract or alcohol extract at 0.05 g/kg and 2 g/kg for 3 weeks, and then, the factors levels related to blood glucose, lipid, free radicals, and even nephropathy were determined. Pathological alterations on liver and kidney were examined. Data showed that, similar to metformin,Cordyceps militarisextracts displayed a significant reduction in blood glucose levels by promoting glucose metabolism and strongly suppressed total cholesterol and triglycerides concentration in serum.Cordyceps militarisextracts exhibit antioxidative effects indicated by normalized superoxide dismutase and glutathione peroxidase levels. The inhibitory effects on blood urea nitrogen, creatinine, uric acid, and protein revealed the protection ofCordyceps militarisextracts against diabetic nephropathy, which was confirmed by pathological morphology reversion. Collectively,Cordyceps militarisextract, a safe pharmaceutical agent, presents excellent antidiabetic and antinephropathic activities and thus has great potential as a new source for diabetes treatment.

scholarly journals Ascorbic Acid-Rich Moringa oleifera Lam. Extract Inhibits Hepatorenal Toxicity and Enhances the Endogenous Antioxidant Levels in Streptozotocin-Induced Type II Diabetes

2019 ◽  
pp. 25-35
Author(s):  
Vikas Kumar ◽  
Ankit Sahoo ◽  
Prakash Khadka ◽  
Deeksha Chauhan ◽  
Azizah Salim Bawadood ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Plasma Insulin ◽  
Moringa Oleifera ◽  
Density Lipoprotein ◽  
Diabetic Rats ◽  
The Body ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Treatment Of Diabetes ◽  
Moringa Oleifera Lam

Background. The cases of diabetes increase day by day due to unhealthy lifestyle, food habit, and less food intake. Novel drugs for the treatment of diabetes are urgently needed. Most researchers are looking for alternative drugs (plant-based drugs) for the treatment of diabetes. Objective. The current experiment was designed to examine the hepatic and renal beneficial effect of Moringa oleifera Lam. (MO) extract in the streptozotocin (STZ)-induced diabetes. Methods. Antidiabetic potential of the MO extract was estimated in terms of blood glucose levels, plasma insulin, hexokinase, and glucose-6-phosphate. Antihyperlipidemic effects of MO extract were evaluated through the estimation of low-density lipoprotein (LDL) cholesterol, total cholesterol (TC), triglyceride (TG), very LDL (VLDL) cholesterol, and high-density lipoprotein (HDL) level whereas the antioxidant effects were evaluated through estimation of catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GPx) levels in diabetic rats. Results. Dose-dependent treatment using MO extract significantly increased the body weight, hexokinase, plasma insulin, HDL, SOD, CAT, and GPx levels (P < 0.001) and significantly decreased the levels of fasting blood glucose, TC, TGs, LDL, VLDL, MDA, fructose-1,6-bisphosphate, glucose-6-phosphate, and glycated hemoglobin in STZ-induced diabetic rats (P < 0.001). Conclusion. MO can be used as a therapeutic agent in the management of elevated blood glucose levels through the alterations in the blood glucose level, plasma level of insulin, and various biochemical parameters.

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