scholarly journals Sustained Liver Glucose Release in Response to Adrenaline Can Improve Hypoglycaemic Episodes in Rats under Food Restriction Subjected to Acute Exercise

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Lucas K. R. Babata ◽  
Maria M. D. Pedrosa ◽  
Rosângela F. Garcia ◽  
Márcia V. Peicher ◽  
Vilma Aparecida Ferreira de Godoi
Keyword(s):  
Blood Glucose ◽  
Food Restriction ◽  
Acute Exercise ◽  
Severe Hypoglycaemia ◽  
Exercise Session ◽  
Glucose Release ◽  
Blood Glucose Profile ◽  
Liver Glycogenolysis ◽  
Liver Response

Background. As the liver is important for blood glucose regulation, this study aimed at relating liver glucose release stimulated by glucagon and adrenaline toin vivoepisodes of hypoglycaemia.Methods. The blood glucose profile during an episode of insulin-induced hypoglycaemia in exercised and nonexercised male Wistar control (GC) and food-restricted (GR, 50%) rats and liver glucose release stimulated by glucagon and adrenaline were investigated.Results. In the GR, the hypoglycaemic episodes showed severe decreases in blood glucose, persistent hypoglycaemia, and less complete glycaemic recovery. An exercise session prior to the episode of hypoglycaemia raised the basal blood glucose, reduced the magnitude of the hypoglycaemia, and improved the recovery of blood glucose. In fed animals of both groups, liver glucose release was activated by glucagon and adrenaline. In fasted GR rats, liver glycogenolysis activated by glucagon was impaired, despite a significant basal glycogenolysis, while an adrenaline-stimulated liver glucose release was recorded.Conclusions. The lack of liver response to glucagon in the GR rats could be partially responsible for the more severe episodes of hypoglycaemia observedin vivoin nonexercised animals. The preserved liver response to adrenaline can partially account for the less severe hypoglycaemia in the food-restricted animals after acute exercise.

P6341Impact of left-ventricular hemodynamics on treadmill exercise intolerance in conscious rats: pilot evaluation in animals with diastolic dysfunction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
B S Ferguson ◽  
N Bennett ◽  
C Zambataro ◽  
R Shimkunas ◽  
C L Del Rio
Keyword(s):  
Heart Rate ◽  
Blood Glucose ◽  
Diastolic Dysfunction ◽  
Exercise Capacity ◽  
Acute Exercise ◽  
Left Ventricular ◽  
Treadmill Running ◽  
Exercise Intolerance ◽  
Volitional Exhaustion

Abstract Introduction Exercise intolerance is a clinical hallmark of patients with hypertrophic cardiomyopathy and/or impaired diastolic function. Elevated LV filling pressures, particularly in response to acute exercise bouts, are thought to play a role limiting exercise capacity in ventricles with abnormal relaxation/compliance. However, it is experimentally difficult to obtain in vivo hemodynamic measures necessary for the evaluation of centrally mediated dysfunction. Leveraging radio-telemetry, we evaluated central hemodynamic parameters as mediators of exercise intolerance in obese ZSF1 rats with diabetes, hypertension, and diastolic dysfunction. Methods Both ZSF1 (637+12g, n=8) and age-matched (28 weeks) healthy control (CTRL, 543+14g, n=4, P<0.05) rats were instrumented for telemetric left-ventricular pressure (LVP) recordings. Following surgical recovery rats were familiarized to treadmill running and subsequently challenged with an exercise protocol aimed at increasing heart rate by 200 beats/min (5° incline, 15 m/min, increased by 3 m/min every 2-min) until volitional exhaustion. LV pressures were collected continuously during cage resting, treadmill resting, and post-exercise until heart rate returned to baseline. Additionally, resting echocardiographic and blood glucose measures were collected. Results At rest, ZSF1 rats had preserved ejection fraction (73+6 vs 79+9%), elevated (P<0.05) blood glucose (237+83 vs 94+23 mg/dL), end-systolic (147+18 vs 103+13 mmHg), and end-diastolic pressures (16+3 vs 9+3 mmHg), with preserved indexed end-diastolic volumes (670+95 vs 741+89 μL/kg), suggesting impaired diastolic compliance. ZSF1 rats terminated exercise prematurely (8:26+1:20 vs 10:27+1:18 min, P<0.05), indicating a limitation in exercise capacity. This early volitional exhaustion was noted while end-diastolic pressures were not further increased (17+7 mmHg), suggesting that other pathological derangement may play a role modulating exercise capacity. For instance, ZSF1 rats tended to have a blunted increase in the systolic index dP/dt40 (+2589+1450 vs +3938+749 mmHg/s, P<0.1) despite achieving comparable increases in HR (193+34 vs 196+38 bpm) with exercise. Conclusion This pilot study demonstrates the feasibility for evaluation of left-ventricular hemodynamics during exercise in rodents with diastolic dysfunction, establishing a platform to evaluate both the mechanisms of exercise intolerance as well as potential therapeutic approaches to rescue exercise capacity. Acknowledgement/Funding MyoKardia

Effect of glucocorticoids on renal net glucose release in vivo in normal and diabetic rats

1983 ◽  
Vol 245 (2) ◽  
pp. F223-F226
Author(s):  
F. Kamiya ◽  
H. Kimura ◽  
T. Takeuchi ◽  
K. Kida ◽  
H. Nakagawa
Keyword(s):  
Blood Glucose ◽  
Normal Control ◽  
Isotope Dilution ◽  
Diabetic Rats ◽  
Isotope Dilution Method ◽  
Dilution Method ◽  
Glucose Release ◽  
Streptozotocin Induced Diabetes ◽  
Adrenalectomized Rats

The effect of glucocorticoids on renal net glucose release in vivo in normal and diabetic rats was studied by the isotope-dilution method. Administration of hydrocortisone to normal fed rats increased renal net glucose release from 0.93 +/- 0.25 to 2.27 +/- 0.21 mg . dl-1 . min-1 and increased its contribution to blood glucose from 27.0 +/- 4.5 to 46.6 +/- 4.0%. The renal net glucose release and its contribution to blood glucose in adrenalectomized rats were 0.40 +/- 0.06 mg . dl-1 . min-1 and 16.3 +/- 1.4%, respectively, significantly less than those of normal control rats, and these parameters were raised to the levels of normal control rats by the administration of hydrocortisone. In rats with streptozotocin-induced diabetes, the renal net glucose release and its contribution to blood glucose were significantly increased to 2.22 +/- 0.51 mg . dl-1 . min-1 and 46.7 +/- 4.9%, respectively, and these parameters were normalized by adrenalectomy. These data indicate that glucocorticoids play an important role in regulation of renal net glucose release and its contribution to blood glucose in both normal and diabetic rats.

scholarly journals Renal Net Glucose Release In Vivo and Its Contribution to Blood Glucose in Rats

1978 ◽  
Vol 62 (4) ◽  
pp. 721-726 ◽  
Author(s):  
Kaichi Kida ◽  
Shinjiro Nakajo ◽  
Fumitada Kamiya ◽  
Yoshiko Toyama ◽  
Takashi Nishio ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Glucose Release

Effects of maleate on carbohydrate metabolism in rats

1976 ◽  
Vol 230 (4) ◽  
pp. 1163-1167 ◽  
Author(s):  
J Rogulski ◽  
A Pacanis ◽  
T Strzelecki ◽  
E Kaminska ◽  
S Angielski
Keyword(s):  
Blood Glucose ◽  
Carbohydrate Metabolism ◽  
Intraperitoneal Administration ◽  
Liver Glycogen ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Renal Gluconeogenesis ◽  
Glycogen Stores ◽  
Liver Glycogenolysis

Intraperitoneal administration of maleate produced an increase in blood alpha-ketoacid, acetoacetate, and free fatty acids. The effect of this treatment on blood glucose levels depended on whether the rats were fed or fasted. In fed rats it was accompanied by slight, transient hyperglycemia connected with depletion of liver glycogen stores. In fasted animals moderate hypoglycemia was observed. The in vivo conversion of various precursors into blood glucose was not inhibited, suggesting that maleate does not affect hepatic gluconeogenesis. Neither was a direct effect on liver glycogenolysis observed. On the other hand, maleate inhibited renal gluconeogenesis from various substrates and stimulated anerobic glycolysis in kidney cortical alices. The data are interpreted in terms of increased utilization and decreased production of glucose by the kidney followed by secondary changes in liver carbohydrate metabolism.

Preparation and Evaluation of Glipizide Tablets Containing both Enhanced and Sustained Release Solid Dispersions

1970 ◽  
Vol 2 (4) ◽  
pp. 714-725
Author(s):  
Adel M. Aly ◽  
Ahmed S. Ali
Keyword(s):  
Blood Glucose ◽  
Blood Glucose Level ◽  
Glucose Level ◽  
Solid Dispersions ◽  
Solvent Evaporation ◽  
In Vivo Studies ◽  
Solvent Evaporation Method ◽  
Evaporation Method ◽  
Tablet Formulations

: Glipizide (GZ) is an oral blood-glucose-lowering drug of the sulfonylurea class characterized by its poor aqueous solubility. Aiming for the production of GZ tablets with rapid onset of action followed by prolonged effect; GZ-Polyethylene glycol (PEG 4000 and 6000) solid dispersions with different ratios, (using melting and solvent evaporation method), as well as, coprecipitate containing GZ with polymethyl-methacrylate (PMMA) were prepared. Four tablet formulations were prepared containing; a) GZ alone, b) GZ: PEG6000, 1:10, c) GZ:PMMA 1:3, and, d)both GZ:PEG6000 1:10 and GZ:PMMA 1:3. The solvent evaporation method showed more enhancement of GZ solubility than the melting one, and this solubilizing effect increased with PEG increment. Generally, PEG6000 showed more enhancement of dissolution than PEG4000 especially at 1:10 drug: polymer ratio (the most enhancing formula). Also, the prepared tablet formulations showed acceptable physical properties according to USP/NF requirements. The dissolution results revealed that tablets containing PEG6000 (1:10) have the most rapid release rate, followed by the formula containing both PEG6000 and PMMA, while that including PMMA alone showed the slowest dissolution rate. Moreover, In-vivo studies for each of the above four formulations, were performed using four mice groups. The most effective formula in decreasing the blood glucose level, through the first 6 hours, was that containing GZ and PEG6000, 1:10. However, formula containing the combination of enhanced and sustained GZ was the most effective in decreasing the blood glucose level through 16 hours. Successful in-vitro in-vivo correlations could be detected between the percent released and the percent decreasing of blood glucose level after 0.5 hours.

Synthesis, Characterization and in vivo Evaluation of PEGylated PPI Dendrimer for Safe and Prolonged Delivery of Insulin

2019 ◽  
Vol 9 (3) ◽  
pp. 248-263 ◽  
Author(s):  
Ashish K. Parashar ◽  
Preeti Patel ◽  
Arun K. Gupta ◽  
Neetesh K. Jain ◽  
Balak Das Kurmi
Keyword(s):  
Blood Glucose ◽  
Drug Release ◽  
Blood Glucose Level ◽  
Glucose Level ◽  
Albino Rats ◽  
Sustained Delivery ◽  
In Vivo Evaluation ◽  
Hemolytic Toxicity

Background: The present study was aimed at developing and exploring the use of PEGylated Poly (propyleneimine) dendrimers for the delivery of an anti-diabetic drug, insulin. Methods: For this study, 4.0G PPI dendrimer was synthesized by successive Michael addition and exhaustive amidation reactions, using ethylenediamine as the core and acrylonitrile as the propagating agent. Two different activated PEG moieties were employed for PEGylation of PPI dendrimers. Various physicochemical and physiological parameters UV, IR, NMR, TEM, DSC, drug entrapment, drug release, hemolytic toxicity and blood glucose level studies of both PEGylated and non- PEGylated dendritic systems were determined and compared. Results: PEGylation of PPI dendrimers caused increased solubilization of insulin in the dendritic framework as well as in PEG layers, reduced drug release and hemolytic toxicity as well as increased therapeutic efficacy with reduced side effects of insulin. These systems were found to be suitable for sustained delivery of insulin by in vitro and blood glucose-level studies in albino rats, without producing any significant hematological disturbances. Conclusion: Thus, surface modification of PPI dendrimers with PEG molecules has been found to be a suitable approach to utilize it as a safe and effective nano-carrier for drug delivery.

In-vitro and in-vivo evaluation of antidiabetic activity of Withania coagulans extract

2019 ◽  
Vol 09 ◽  
Author(s):  
Tejas Patel ◽  
B.N. Suhagia
Keyword(s):  
Blood Glucose ◽  
Acute Toxicity ◽  
Aqueous Extract ◽  
Pancreatic Beta Cell ◽  
Toxicity Study ◽  
Acute Toxicity Study ◽  
Withania Coagulans ◽  
Study Results

Background: Diabetes mellitus is major issue to public health as its prevalence is rising day by day. Synthetic agents available for the diabetic treatment are expensive or produce undesirable side effect on chronic use and some of them are not suitable during pregnancy. Herbal medicines accepted widely due to side effects and low cost. Objective: The aim of present study was to evaluate the activity of Withania coagulans extract using In-vitro and In-vivo model. Methods: Different three types of Withania coagulans extract were prepared using aqueous (W1), Alcohol (W2) and hydro-alcoholic (50:50) mixture (W3). In-vitro Anti-diabetic activity of the all three extracts evaluated using RINm5F Pancreatic beta cells.Further, n-vivo anti-diabetic evaluation performed by administering 50 mg/kg (p.o) aqueous extract for 7 days in Streptozotocin (STZ)-induced mice. Body weight of the animals was also determined to perform acute toxicity study. Results: The results of in –vitro cell based study indicated that among all three extract, aqueous extract (W1) of Withania coagulans showed potential increase in inulin release. The EC50 of the W1 (249.6 µg/L) which is compared with standard (Glibenclamide) EC50. From the results of In-vitro study, W1 subjected for acute toxicity study and the acute toxicity study results indicated LD50 of 50mg/kg. Diabetic rats treated with W1 extract at oral dose of 50 mg/kg for 7 days showed 34.17% reduction in blood glucose in comparison to untreated diabetic (STZ-induced) rats. Blood glucose levels of Standard treated (Glibenclamide) and control untreated. Conclusion: In conclusion, results of pancreatic beta cell based study showed increase in insulin release by administration of extract. Further aqueous extract (W1) was potentially reduced blood glucose level in STZ induced diabetic mice.

scholarly journals Pharmacoinformatics and UPLC-QTOF/ESI-MS-Based Phytochemical Screening of Combretum indicum against Oxidative Stress and Alloxan-Induced Diabetes in Long–Evans Rats

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4634
Author(s):  
Md. Shaekh Forid ◽  
Md. Atiar Rahman ◽  
Mohd Fadhlizil Fasihi Mohd Aluwi ◽  
Md. Nazim Uddin ◽  
Tapashi Ghosh Roy ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Immune Modulation ◽  
Computational Study ◽  
Density Lipoprotein ◽  
Control Group ◽  
Esi Ms ◽  
Long Evans ◽  
Antidiabetic Effects

This research investigated a UPLC-QTOF/ESI-MS-based phytochemical profiling of Combretum indicum leaf extract (CILEx), and explored its in vitro antioxidant and in vivo antidiabetic effects in a Long–Evans rat model. After a one-week intervention, the animals’ blood glucose, lipid profile, and pancreatic architectures were evaluated. UPLC-QTOF/ESI-MS fragmentation of CILEx and its eight docking-guided compounds were further dissected to evaluate their roles using bioinformatics-based network pharmacological tools. Results showed a very promising antioxidative effect of CILEx. Both doses of CILEx were found to significantly (p < 0.05) reduce blood glucose, low-density lipoprotein (LDL), and total cholesterol (TC), and increase high-density lipoprotein (HDL). Pancreatic tissue architectures were much improved compared to the diabetic control group. A computational approach revealed that schizonepetoside E, melianol, leucodelphinidin, and arbutin were highly suitable for further therapeutic assessment. Arbutin, in a Gene Ontology and PPI network study, evolved as the most prospective constituent for 203 target proteins of 48 KEGG pathways regulating immune modulation and insulin secretion to control diabetes. The fragmentation mechanisms of the compounds are consistent with the obtained effects for CILEx. Results show that the natural compounds from CILEx could exert potential antidiabetic effects through in vivo and computational study.

Sequoyitol ameliorates diabetic nephropathy in diabetic rats induced with a high-fat diet and a low dose of streptozotocin

2014 ◽  
Vol 92 (5) ◽  
pp. 405-417 ◽  
Author(s):  
Xian-Wei Li ◽  
Yan Liu ◽  
Wei Hao ◽  
Jie-Ren Yang
Keyword(s):  
Diabetic Nephropathy ◽  
Blood Glucose ◽  
High Fat Diet ◽  
Low Dose ◽  
Serum Insulin ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
High Fat

Sequoyitol decreases blood glucose, improves glucose intolerance, and enhances insulin signaling in ob/ob mice. The aim of this study was to investigate the effects of sequoyitol on diabetic nephropathy in rats with type 2 diabetes mellitus and the mechanism of action. Diabetic rats, induced with a high-fat diet and a low dose of streptozotocin, and were administered sequoyitol (12.5, 25.0, and 50.0 mg·(kg body mass)−1·d−1) for 6 weeks. The levels of fasting blood glucose (FBG), serum insulin, blood urea nitrogen (BUN), and serum creatinine (SCr) were measured. The expression levels of p22phox, p47phox, NF-κB, and TGF-β1 were measured using immunohistochemisty, real-time PCR, and (or) Western blot. The total antioxidative capacity (T-AOC), as well as the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) were also determined. The results showed that sequoyitol significantly decreased FBG, BUN, and SCr levels, and increased the insulin levels in diabetic rats. The level of T-AOC was significantly increased, while ROS and MDA levels and the expression of p22phox, p47phox, NF-κB, and TGF-β1 were decreased with sequoyitol treatment both in vivo and in vitro. These results suggested that sequoyitol ameliorates the progression of diabetic nephropathy in rats, as induced by a high-fat diet and a low dose of streptozotocin, through its glucose-lowering effects, antioxidant activity, and regulation of TGF-β1 expression.

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