scholarly journals Novel pentacyclic triterpene isolated from seeds of Euryale Ferox Salisb. ameliorates diabetes in streptozotocin induced diabetic rats

2018 ◽  
Vol 11 (4) ◽  
pp. 275-288 ◽  
Author(s):  
Danish Ahmed ◽  
Mohd. Ibrahim Khan ◽  
Manju Sharma ◽  
Mohd. Faiyaz Khan
Keyword(s):  
Glycemic Control ◽  
Plasma Insulin ◽  
Glycosylated Hemoglobin ◽  
Diabetic Rats ◽  
Active Principle ◽  
Pentacyclic Triterpene ◽  
Morphological Alterations ◽  
Euryale Ferox ◽  
Liver And Kidney ◽  
Glucose 6 Phosphate Dehydrogenase

Abstract The present research was carried out to study the effect of 2β-hydroxybetulinic acid 3β-oleiate (HBAO), a novel compound isolated from the seeds of Euryale ferox salisb. on glycemic control, antioxidant status and histopathological morphological alterations in the liver, pancreas, kidney and heart in streptozotocin induced type-2 diabetes in rats. HBAO was isolated from the seeds of Euryale ferox salisb. according to Lee. Isolation of the active principle HBAO was performed for the first time. To date there are no reports on the isolation and evaluation of 2β-hydroxybetulinic acid 3β-oleiate (HBAO) from Euryale ferox salisb. Assessment of different biochemical parameters like the effect of HBAO on glycemic control, plasma insulin, glycosylated hemoglobin, hepatic glucose-6-phosphate dehydrogenase, glucose-6-phosphatase and fructose-1-6-biphosphatase, hepatic hexokinase, lipid profile, antioxidant marker and histopathology of pancreas, liver and kidney examination was done at the end of the experimentation, i.e. on day 45. HBAO exhibited remarkable improvement in glycemic control, lipid levels, plasma insulin, glycogenic liver enzymes and antioxidant activity in diabetic rats, along with progressive enhancement of distortive histopathological morphology of liver, pancreas and kidney. The results strongly suggest that HBAO could be a potential therapeutic agent in diabetes.

scholarly journals Anti-Diabetic Potential of the Leaves of Anisomeles malabarica in Streptozotocin Induced Diabetic Rats

2017 ◽  
Vol 43 (4) ◽  
pp. 1689-1702 ◽  
Author(s):  
Peddanna Kotha ◽  
Kameswara Rao Badri ◽  
Ramya Nagalapuram ◽  
Rajasekhar Allagadda ◽  
Appa Rao Chippada
Keyword(s):  
Diabetes Mellitus ◽  
Glucose Tolerance ◽  
Ethyl Acetate ◽  
Plasma Insulin ◽  
Ethyl Acetate Extract ◽  
Glycosylated Hemoglobin ◽  
Diabetic Rats ◽  
Active Fraction ◽  
Insulin Levels ◽  
Plasma Insulin Levels

Background/Aims: Diabetes mellitus is a pandemic metabolic disorder that is affecting a majority of populations in recent years. There is a requirement for new drugs that are safer and cheaper due to the side effects associated with the available medications. Methods: We investigated the anti-diabetic activity of leaves of Anisomeles malabarica following bioactivity guided fractionation. The different solvent (hexane, ethyl acetate, methanol and water) extracts of A. malabarica leaves were used in acute treatment studies to evaluate and identify the active fraction. The ethyl acetate extract was subjected to further fractionation using silica gel column chromatography and the compounds were identified by LC-SRM/MS and GC-MS. Additional chronic treatment studies were carried out using this active fraction (AMAF) for 30 days in experimental diabetic rats. Fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), plasma insulin levels and glucose tolerance were measured along with insulin resistance/sensitivity indicators (HOMA-IR, HOMA-β and QUICKI) to assess the beneficial effects of A. malabarica in the management of diabetes mellitus. Results: Among the different solvent extracts tested, ethyl acetate extract showed maximum (66%) anti-hyperglycemic activity. The hexane and ethyl acetate (1: 1) fraction that has maximum anti-diabetic activity was identified as active fraction of A. malabarica (AMAF). The FBG, HbA1c, plasma insulin levels and insulin sensitivity/resistance indicators such as glucose tolerance, HOMA-IR, HOMA-β and QUICKI were significantly improved to near normal in diabetic rats treated with AMAF. Further, we identified key flavonoids and fatty acids as the anti-diabetic active principles from the AMAF of A. malabarica leaves. Conclusion: The results of our study suggest that Anisomeles malabarica has potential anti-diabetic activity in STZ induced diabetic rats.

Eudragit L-100 Capsules Aromatize and Quaternerize Chitosan for Insulin Nanoparticle Oral Delivery During Toxic Oxidative Stress in Rat Liver and Kidney

2020 ◽  
Vol 8 (3) ◽  
pp. 239-254 ◽  
Author(s):  
Reza Mahjub ◽  
Farzane K. Najafabadi ◽  
Narges Dehkhodaei ◽  
Nejat Kheiripour ◽  
Amir N. Ahmadabadi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oral Administration ◽  
Oral Delivery ◽  
Biochemical Parameters ◽  
Kidney Injury ◽  
Regular Insulin ◽  
Treated Group ◽  
Histopathological Change ◽  
Diabetic Rats ◽  
Liver And Kidney

Background: Insulin, like most peptides, is classified as a hydrophilic and macromolecular drug that is considered as a low permeable and unstable compound in the gastrointestinal (GI) tract. The acidic condition of the stomach can degrade insulin molecules. Moreover, the presence of proteolytic activities of some enzymes such as trypsin and chymotrypsin can hydrolyze amide-bonds between various amino-acids in the structures of peptides and proteins. However, due to its simplicity and high patient compliance, oral administration is the most preferred route of systemic drug delivery, and for the development of an oral delivery system, some obstacles in oral administration of peptides and proteins including low permeability and low stability of the proteins in GI should be overcome. Objective: In this study, the effects of orally insulin nanoparticles (INPs) prepared from quaternerized N-aryl derivatives of chitosan on the biochemical factors of the liver in diabetic rats were studied. Methods: INPs composed of methylated (amino benzyl) chitosan were prepared by the PEC method. Lyophilized INPs were filled in pre-clinical capsules, and the capsules were enteric-coated with Eudragit L100. Twenty Male Wistar rats were randomly divided into four groups: group1: normal control rats, group 2: diabetic rats, group 3: diabetic rats received capsules INPs(30 U/kg/day, orally), group 4: the diabetic rats received regular insulin (5 U/kg/day, subcutaneously). At the end of the treatment, serum, liver and kidney tissues were collected. Biochemical parameters in serum were measured using spectrophotometric methods. Also, oxidative stress was measured in plasma, liver and kidney. Histological studies were performed using H and E staining . Results: Biochemical parameters, and liver and kidney injury markers in serum of the diabetic rats that received INPs improved significantly compared with the diabetic group. INPs reduced oxidative toxic stress biomarkers in serum, liver and kidney of the diabetic treated group. Furthermore, a histopathological change was developed in the treated groups. Conclusion: Capsulated INPs can prevent diabetic liver and oxidative kidney damages (similar regular insulin). Therefore oral administration of INPs appears to be safe. Lay Summary: Although oral route is the most preferred route of administration, but oral delivery of peptides and proteins is still a challenging issue. Diabetes Mellitus may lead to severe complications, which most of them are life-threatening. In this study, we are testing the toxicity of oral insulin nanoparticles in kidney and liver of rats. For this investigation, we will prepare insulin nanoparticles composed of a quaternized derivative of chitosan. The nanoparticles will be administered orally to rats and the level of oxidative stress in their liver and kidney will be determined. The data will be compared to the subcutaneous injection of insulin.

Vasopressin V1 and V2 receptors in diabetes mellitus

1994 ◽  
Vol 266 (2) ◽  
pp. E217-E223 ◽  
Author(s):  
D. Trinder ◽  
P. A. Phillips ◽  
J. M. Stephenson ◽  
J. Risvanis ◽  
A. Aminian ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Inositol Phosphate ◽  
Free Water ◽  
Diabetic Rats ◽  
Biological Responses ◽  
Liver And Kidney ◽  
Streptozotocin Induced Diabetes ◽  
V2 Receptor ◽  
Plasma Arginine ◽  
Long Acting

Diabetes mellitus causes hypertonicity, increased plasma arginine vasopressin (AVP), polydipsia, and polyuria. Downregulation of AVP V2 receptors may contribute to the polyuria through diminished V2 receptor-mediated free water retention. After 2 wk of streptozotocin-induced diabetes mellitus, the diabetic rats had raised plasma glucose, AVP, and osmolality levels (P < 0.001) compared with nondiabetic controls (Sham). Insulin treatment (4 U long-acting insulin sc, daily) partially lowered these values (P < 0.01). There was a reduction in the number of renal and hepatic V1 receptors in the diabetic and diabetic+insulin animals compared with the sham animals (P < 0.05). The receptor affinity remained unchanged. In parallel, there was a reduction in maximum AVP-activated total inositol phosphate production in the liver and kidney of the diabetic and diabetic+insulin animals compared with the sham animals (P < 0.05). The density and affinity of renal V2 receptors and AVP-stimulated adenosine 3',5'-cyclic monophosphate production in the diabetic and diabetic+insulin animals were unchanged compared with the sham. These results demonstrate differential regulation of AVP receptors and suggest that downregulation of renal V2 receptors does not contribute to the polyuria of diabetes. In contrast, downregulation of V1 receptors might contribute to diminished V1 receptor-mediated biological responses to AVP seen in diabetes mellitus.

scholarly journals The Insulin Receptor Mediates Insulin’s Early Plasma Clearance by Liver, Muscle, and Kidney

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 37
Author(s):  
Rick I. Meijer ◽  
Eugene J. Barrett
Keyword(s):  
Insulin Receptor ◽  
Plasma Clearance ◽  
Plasma Insulin ◽  
Insulin Clearance ◽  
Initial Plasma ◽  
Liver And Kidney ◽  
Pre Treatment ◽  
Initial Clearance

The role of the insulin receptor in mediating tissue-specific insulin clearance in vivo has not been reported. Using physiologic insulin doses, we measured the initial clearance rate (first 5 min) of intravenously injected ([125I]TyrA14)-insulin by muscle, liver, and kidney in healthy rats in the presence and absence of the insulin receptor blocker S961. We also tested whether 4 weeks of high-fat diet (HFD) affected the initial rate of insulin clearance. Pre-treatment with S961 for 60 min prior to administering labeled insulin raised plasma ([125I]TyrA14)insulin concentration approximately 5-fold (p < 0.001), demonstrating receptor dependency for plasma insulin clearance. Uptake by muscle (p < 0.01), liver (p < 0.05), and kidney (p < 0.001) were each inhibited by receptor blockade, undoubtedly contributing to the reduced plasma clearance. The initial plasma insulin clearance was not significantly affected by HFD, nor was muscle-specific clearance. However, HFD modestly decreased liver clearance (p = 0.056) while increasing renal clearance by >50% (p < 0.01), suggesting a significant role for renal insulin clearance in limiting the hyperinsulinemia that accompanies HFD. We conclude that the insulin receptor is a major mediator of initial insulin clearance from plasma and for its clearance by liver, kidney, and muscle. HFD feeding increases renal insulin clearance to limit systemic hyperinsulinemia.

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