Multivesicular Liposomes for Glucose-Responsive Insulin Delivery

An intelligent insulin delivery system is highly desirable for diabetes management. Herein, we developed a novel glucose-responsive multivesicular liposome (MVL) for self-regulated insulin delivery using the double emulsion method. Glucose-responsive MVLs could effectively regulate insulin release in response to fluctuating glucose concentrations in vitro. Notably, in situ released glucose oxidase catalyzed glucose enrichment on the MVL surface, based on the combination of (3-fluoro-4-((octyloxy)carbonyl)phenyl)boronic acid and glucose. The outer MVL membrane was destroyed when triggered by the local acidic and H2O2-enriched microenvironment induced by glucose oxidase catalysis in situ, followed by the further release of entrapped insulin. Moreover, the Alizarin red probe and molecular docking were used to clarify the glucose-responsive mechanism of MVLs. Utilizing chemically induced type 1 diabetic rats, we demonstrated that the glucose-responsive MVLs could effectively regulate blood glucose levels within a normal range. Our findings suggest that glucose-responsive MVLs with good biocompatibility may have promising applications in diabetes treatment.

Download Full-text

Study of Antihyperglycemic, Antihyperlipidemic and Antioxidant Activities of Tannins Extracted from Warionia saharae Benth. & Coss

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530318666181029160539 ◽

2019 ◽

Vol 19 (2) ◽

pp. 189-198 ◽

Cited By ~ 3

Author(s):

Mohammed Ajebli ◽

Fadwa El Ouady ◽

Mohamed Eddouks

Keyword(s):

Antioxidant Activity ◽

Antioxidant Activities ◽

Histopathological Examination ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Diabetic Rats ◽

Lipid Lowering ◽

Glucose Levels ◽

Soxhlet Apparatus

Background and Objective: Warionia saharae Benth & Coss, a plant belonging to Asteraceae family, is used for its anti-diabetic properties in Morocco. The objective of this study was to evaluate the effect of tannins extracted from Warionia saharae (W. saharae) on blood glucose levels and lipid profile in normal and streptozotocin(STZ)-induced diabetic rats. Methods: Tannins (TE) were extracted from W. saharae using Soxhlet apparatus and different organic solvents. Single and once daily repeated oral administration of TE (10 mg/kg) for 15 days were used to evaluate the glucose and lipid-lowering activity in normal and diabetic rats. Furthermore, glucose test tolerance, liver histopathological examination and in vitro antioxidant activity of TE were carried out in this study. Results: The results showed that TE was able to exert antihyperglycemic and lowering total cholesterol effects as well as improvement of the high-density lipoprotein (HDL)-cholesterol serum level after 15 days of treatment. Furthermore, TE improved glucose tolerance, histopathological status of liver in diabetic rats and demonstrated interesting antioxidant activity. Conclusion: In conclusion, the present investigation revealed that TE possesses potent antidiabetic and antihyperlipidemic activities as claimed in different ethnopharmacological practices.

Download Full-text

Chenopodium quinoa Exhibits Antihyperglycemic Activity in Streptozotocin-Induced Diabetic Rats

Cardiovascular & Hematological Agents in Medicinal Chemistry ◽

10.2174/1871525719666210812094837 ◽

2021 ◽

Vol 19 ◽

Author(s):

Amine Azzane ◽

Ayou Amssayef ◽

Mohame Eddouks

Keyword(s):

Antioxidant Activity ◽

Aqueous Extract ◽

Histopathological Examination ◽

Chenopodium Quinoa ◽

Diabetic Rats ◽

Favorable Effect ◽

Antihyperglycemic Activity ◽

Glucose Levels ◽

Blood Glucose Levels

Aims: The aim of the study was to evaluate the antihyperglycemic effect of Chenopodium quinoa. Background: Chenopodium quinoa is a pseudocereal plant with several medicinal properties. Objective: The goal of this investigation was to determine the antihyperglycemic activity of Chenopodium quinoa in both normal and streptozotocin(STZ)-induced diabetic rats. Methods: In this study, the effect of the aqueous extract of Chenopodium quinoa seeds (AECQS) (60 mg/kg) on blood glucose levels was evaluated in both normal and diabetic rats after a single (6 hours) and repeated oral administration (7 days of treatment). The effect of this herb on glucose tolerance and lipid profile was also studied. Additionally, histopathological examination of liver was carried out using the Hematoxylin-Eosin method. Furthermore, the in vitro antioxidant activity as well as a preliminary phytochemical screening and quantification of some secondary metabolites (phenolic compounds, flavonoids and tannins) were performed according to standard methods. Results: AECQS produced a significant lowering effect on plasma glucose levels in STZ-induced diabetic rats. In addition, this extract exhibited a remarkable amelioration on hepatic histopathology in diabetic rats. In addition, the extract exerted a remarkable antioxidant activity which could be due to the presence of some compounds found in this herb. Conclusion: In conclusion, this study demonstrates that the aqueous extract of Chenopodium quinoa seeds has a favorable effect in controlling diabetes mellitus.

Download Full-text

Exosome-Mediated Insulin Delivery for the Potential Treatment of Diabetes Mellitus

Pharmaceutics ◽

10.3390/pharmaceutics13111870 ◽

2021 ◽

Vol 13 (11) ◽

pp. 1870

Author(s):

Belén Rodríguez-Morales ◽

Marilena Antunes-Ricardo ◽

José González-Valdez

Keyword(s):

Diabetes Mellitus ◽

Human Insulin ◽

Insulin Delivery ◽

Dermal Fibroblasts ◽

Therapeutic Drug ◽

Extracellular Medium ◽

Glucose Levels ◽

Wide Range ◽

Diabetes Mellitus Treatment

Exosomes are extracellular nanovesicles between 30 and 150 nm that serve as essential messengers for different biological signaling and pathological processes. After their discovery, a wide range of applications have been developed, especially in therapeutic drug delivery. In this context, the aim of this work was to test the efficiency of exosome-mediated human insulin delivery using exosomes extracted from three different cell lines: hepatocellular carcinoma (HepG2); primary dermal fibroblasts (HDFa) and pancreatic β cells (RIN-m); all are related to the production and/or the ability to sense insulin and to consequently regulate glucose levels in the extracellular medium. The obtained results revealed that the optimal insulin loading efficiency was achieved by a 200 V electroporation, in comparison with incubation at room temperature. Moreover, the maximum in vitro exosome uptake was reached after incubation for 6 h, which slightly decreased 24 h after adding the exosomes. Glucose quantification assays revealed that exosome-mediated incorporation of insulin presented significant differences in HDFa and HepG2 cells, enhancing the transport in HDFa, in comparison with free human insulin effects in the regulation of extracellular glucose levels. No significant differences were found between the treatments in RIN-m cells. Hence, the results suggest that exosomes could potentially become a valuable tool for stable and biocompatible insulin delivery in diabetes mellitus treatment alternatives.

Download Full-text

Maintaining a Physiological Blood Glucose Level with ‘Glucolevel’, a Combination of Four Anti-Diabetes Plants Used in the Traditional Arab Herbal Medicine

Evidence-based Complementary and Alternative Medicine ◽

10.1093/ecam/nem047 ◽

2008 ◽

Vol 5 (4) ◽

pp. 421-428 ◽

Cited By ~ 57

Author(s):

Omar Said ◽

Stephen Fulder ◽

Khaled Khalil ◽

Hassan Azaizeh ◽

Eli Kassis ◽

...

Keyword(s):

Juglans Regia ◽

Human Fibroblasts ◽

Tolerance Test ◽

Positive Control ◽

Diabetic Rats ◽

Yeast Cells ◽

Sugar Uptake ◽

Glucose Levels

Safety and anti-diabetic effects of Glucolevel, a mixture of dry extract of leaves of theJuglans regiaL,Olea europeaL,Urtica dioicaL andAtriplex halimusL were evaluated usingin vivoandin vitrotest systems. No sign of toxic effects (using LDH assay) were seen in cultured human fibroblasts treated with increasing concentrations of Glucolevel. Similar observations were seenin vivostudies using rats (LD50: 25 g/kg). Anti-diabetic effects were evidenced by the augmentation of glucose uptake by yeast cells (2-folds higher) and by inhibition of glucose intestinal absorption (∼49%) in a rat gut-segment. Furthermore, treatment with Glucolevel of Streptozotocin-induced diabetic rats for 2–3 weeks showed a significant reduction in glucose levels [above 400 ± 50 mg/dl to 210 ± 22 mg/dl (P< 0.001)] and significantly improved sugar uptake during the glucose tolerance test, compared with positive control. In addition, glucose levels were tested in sixteen human volunteers, with the recent onset of type 2 diabetes mellitus, who received Glucolevel tablets 1 × 3 daily for a period of 4 weeks. Within the first week of Glucolevel consumption, baseline glucose levels were significantly reduced from 290 ± 40 to 210 ± 20 mg/dl. At baseline, a subgroup of eleven of these subjects had glucose levels below 300 mg% and the other subgroup had levels ≥ 300 mg%. Clinically acceptable glucose levels were achieved during the 2–3 weeks of therapy in the former subgroup and during the 4th week of therapy in the latter subgroup. No side effect was reported. In addition, a significant reduction in hemoglobin A1C values (8.2 ± 1.03 to 6.9 ± 0.94) was found in six patients treated with Glucolevel. Results demonstrate safety, tolerability and efficacy of herbal combinations of four plants that seem to act differently but synergistically to regulate glucose-homeostasis.

Download Full-text

Impaired Relaxation in Aorta from Streptozotocin-diabetic Rats: Effect of Aminoguanidine (AMNG) Treatment

International Journal of Experimental Diabetes Research ◽

10.1155/edr.2000.145 ◽

2000 ◽

Vol 1 (2) ◽

pp. 145-153 ◽

Cited By ~ 7

Author(s):

Sibel Özyazgan ◽

Yesim Unlucerci ◽

Selda Bekpinar ◽

Ahmet Gökhan Akkan

Keyword(s):

Drinking Water ◽

Product Formation ◽

Diabetic Rats ◽

Glucose Levels ◽

Vasoactive Substances ◽

Blood Glucose Levels ◽

Body Weights ◽

Endothelium Dependent Relaxation ◽

Advanced Glycosylation

AimThe effect of 8 weeks′ streptozotocin (STZ)- induced diabetes and aminoguanidine (AMNG), the inhibitor of advanced glycosylation reaction, treatment on arteriolar reactivity to vasoactive substances was investigatedin vitro.Materials and MethodsStudies were performed in untreated control rats (n= 10), STZ-induced (60 mg/kg i.v.) diabetic rats (n= 10), AMNG-treated (600 mg/l given in drinking water throughout 8 weeks) control rats (n= 10) and AMNG-treated (600 mg/l given in drinking water, beginning at 72h after STZ and throughout 8 weeks of diabetes) diabetic rats (n= 10). Results are expressed as the mean ±s.e. Relaxant responses are expressed as a percentage (%) relaxation of noradrenaline-induced tone. Statistical comparisons were made by one-way analysis of variance (ANOVA) followed by Tukey–Kramer multiple comparisons test.Results1. The decreased body weights (205 ± 6 g) and increased blood glucose levels (583 ± 8 mg/dl) of diabetic rats were partially restored by treatment of aminoguanidine (253 ± 6 g,p< 0.05 and 480 ± 14 mg/dl,p< 0.001, respectively). 2. Diabetes caused a 71% deficit in maximal endothelium-dependent relaxation to acetylcholine for noradrenaline precontracted aortas (p< 0.001). AMNG treatment prevented the diabetes-induced impairment in endothelium dependent relaxation (58 ± 8%) to acetylcholine, maximum relaxation remaining in the non-diabetic range (78 ± 4%). 3. Neither diabetes nor treatment affected endothelium-independent relaxation (pD2and max. Relax.) to sodium nitroprusside. 4. Vasoconstrictor responses (pD2and Max. Contraction) to noradrenaline and KCl were not influenced by the diabetic state and treatment.ConclusionOur data suggest that 8 weeks of experimental diabetes is associated with a decreased endothelium-dependent vasodilatation. AMNG treatment may prevent diabetes-induced endothelial dysfunction. This may be mediatedviathe prevention of advanced glycosylation end product formation, the enhanced release of vasodilator substances such as prostacyclin, the increased elasticity of blood vessels, the antioxidant activity and inhibitor activity of enzyme aldose-reductase by AMNG.

Download Full-text

Efficiency of a formulated condiment (duqqa) in mitigation of diabetes and its complications induced by streptozotocin-nicotinamide in rats

Journal of Herbmed Pharmacology ◽

10.34172/jhp.2021.24 ◽

2021 ◽

Vol 10 (2) ◽

pp. 218-225

Author(s):

Rasha S. Mohamed ◽

Ahmed M. Abdel-Salam

Keyword(s):

Diabetes Management ◽

Diabetic Control ◽

Black Pepper ◽

Diabetic Rats ◽

Glucose Levels ◽

Balanced Diet ◽

Liver And Kidney ◽

Onset Of Diabetes ◽

Date Seeds Powder ◽

Kidney Functions

Introduction: Duqqa is a condiment, consisting of black pepper, cumin, sesame, coriander and high amount of salt. Reducing salt and adding other beneficial items to traditional duqqa can make it suitable dietary supplement for diabetes management. The current study aimed to assess the effect of a modified duqqa on diabetes and its complications in diabetic rats. Methods: The modified duqqa was formulated by mixing grounded fermented wheat, sesame, coriander, cumin, chicory leaves, cinnamon, turmeric and date seeds powder and studied in diabetic rats which were developed by streptozotocin-nicotinamide injection. Thirty-two rats were divided into four groups (n = 8) including non-diabetic, diabetic control and the other two groups fed on balanced diet supplemented with either 10 or 20% of duqqa prior the induction of diabetes (for one week) to the end of the experiment (8 weeks). Results: The dietary supplementation with 10 and 20% of the formulated duqqa prior the induction of diabetes did not delay the onset of diabetes in rats but produced reduction (32.56% and 50.47%, respectively) in the glucose levels of diabetic rats. Also, diabetic rats fed on the formulated duqqa showed insulin concentrations higher than that of diabetic control rats. Feeding diabetic rats on the formulated duqqa reversed the elevation of kidney lipid peroxidation and nitric oxide, limited the disturbance in the lipid profile as well as liver and kidney functions and elevated both serum and femur magnesium concentrations. Conclusion: The results indicated the hypoglycemic effect of the formulated duqqa and its efficiency in delaying diabetes complications.

Download Full-text

“Oil-soluble” Reversed Lipid Nanoparticles for Oral Insulin Delivery

10.21203/rs.3.rs-25661/v1 ◽

2020 ◽

Author(s):

Tao Wang ◽

Dongqin Quan

Keyword(s):

Oral Absorption ◽

Insulin Delivery ◽

Lipid Nanoparticles ◽

Oral Insulin ◽

Glucose Levels ◽

Blood Glucose Levels ◽

Transmission Electron ◽

Insulin Solution

Abstract Background In this study, we aimed to design a novel oral insulin delivery system, named “oil-soluble” reversed lipid nanoparticles (ORLN), in which a hydrophilic insulin molecule is encapsulated by a phospholipid (PC) shell and dissolved in oil to prevent the enzymatic degradation of insulin. ORLN was characterized by transmission electron microscopy and dynamic light scattering. Results In vitro enzymatic stability studies showed higher concentrations of insulin in cells incubated with ORLN-encapsulated insulin than in those incubated with free insulin solution in artificial intestinal fluid (pH 6.5). The protective effect of ORLN was attributed to its special release behavior and the formulation of the PC shell and oil barrier. Furthermore, an in vivo oral efficacy study confirmed that blood glucose levels were markedly decreased after ORLN administration in both healthy and diabetic mice. In vivo pharmacokinetic results showed that the bioavailability of ORLN-conjugated insulin was approximately 28.7% relative to that of the group subcutaneously administered with an aqueous solution of insulin, indicating enhanced oral absorption. Conclusions In summary, the ORLN system developed here shows promise as a nanocarrier for improving the oral absorption of insulin.

Download Full-text

Antihyperglycemic potential of Matricaria pubescens(Desf.) Schultz. in streptozotocin-induced diabetic rats

Cardiovascular & Haematological Disorders - Drug Targets ◽

10.2174/1871529x20666200630112610 ◽

2020 ◽

Vol 20 ◽

Author(s):

Ayoub Amssayef ◽

Mohammed Ajebli ◽

Mohamed Eddouks

Keyword(s):

Aqueous Extract ◽

Aerial Part ◽

Histopathological Examination ◽

Diabetic Rats ◽

Glucose Levels ◽

Blood Glucose Levels ◽

Liver And Pancreas ◽

Treatment Of Diabetes ◽

Antioxidant Effects

Aims: The aim of the study was to investigate the antihyperglycemic activity of Matricaria pubescens. Background: Matricaria pubescens (Def). Shultz (Asteraceae) is commonly used traditionally for the treatment of diabetes in Morocco. Objective: This present investigation aimed to assess the antihyperglycemic and antioxidant effects of the aqueous extract of aerial part of Matricaria pubescens (M. pubescens). Methods: The effect of a single and repeated oral administration of the aqueous extract of aerial part of M. pubescens (AEAPMP) at a dose of 40 mg/kg on glucose was examined in normal and streptozotocin-induced diabetic rats. Additionally, histopathological examination of pancreas and liver was carried out according to the Hematoxylin-Eosin method. The antioxidant activity was performed using the DPPH assay. Results: The results showed that the aqueous extract of M. pubescens (AEAPMP) exhibited a significant lowering activity on blood glucose levels in STZ-induced diabetic rats. In addition, AEAPMP ameliorated the histopathological tissues of liver and pancreas. Furthermore, a potential in vitro antioxidant of AEAPMP has been shown. Conclusion: In conclusion, this study demonstrates that M. pubescens possesses a beneficial effect against hyperglycemia associated with diabetes.

Download Full-text

Possible role of blood insulin levels on glutathione S-transferase activities from different tissues of male rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y90-027 ◽

1990 ◽

Vol 68 (2) ◽

pp. 170-173 ◽

Cited By ~ 3

Author(s):

Cristina E. Carnovale ◽

Juan A. Monti ◽

Viviana A. Catania ◽

Maria C. Carrillo

Keyword(s):

Diabetic Rats ◽

Male Rats ◽

Blood Levels ◽

Transferase Activity ◽

Glutathione S Transferase ◽

Insulin Levels ◽

Blood Insulin ◽

Glucose Levels

The activity of in vitro glutathione S-transferase towards 1-chloro-2,4-dinitrobenzene was examined in liver, renal cortex, and small intestine (duodenum, jejunum, ileum) after the in vivo treatment of male Wistar rats with streptozotocin or alloxan. The studies were performed at 2, 10, 24, and 48 h and 7 and 15 days after streptozotocin treatment or 24 and 48 h after alloxan treatment. The results indicated that while the blood levels of insulin–glucose did not show variations, there were no alterations of the glutathione S-transferase activity in the tissues tested. On the other hand, when the treatments caused modifications on blood insulin–glucose levels, there were changes of glutathione S-transferase activity in all tissues (except in the ileum) in such a way that a direct relationship between plasma insulin levels and glutathione S-transferase activity could be demonstrated. These results were also confirmed through insulin administration to control and diabetic rats. The data demonstrate a possible regulation of glutathione S-transferase activity by blood insulin and (or) glucose levels in the tissues tested.Key words: insulin, glutathione S-transferase, streptozotocin, alloxan.

Download Full-text

Evaluation ofMallotus oppositifoliusMethanol Leaf Extract on the Glycaemia and Lipid Peroxidation in Alloxan-Induced Diabetic Rats: A Preliminary Study

Biochemistry Research International ◽

10.1155/2013/527205 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

C. O. Nwaehujor ◽

I. I. Ezeigbo ◽

F. C. Nwinyi

Keyword(s):

Lipid Peroxidation ◽

Antioxidant Activity ◽

Blood Glucose ◽

Oral Treatment ◽

Fasting Blood Glucose ◽

Diabetic Rats ◽

Albino Rats ◽

Glucose Levels ◽

Blood Glucose Levels

Objective. Mallotus oppositifolius(Geiseler) Müll. Arg. (Euphorbiaceae) is folklorically used to “treat” diabetic conditions in some parts of Nigeria therefore the study, to investigate the extract of the leaves for activities on hyperglycaemia, lipid peroxidation, and increased cholesterol levelsin vivoin alloxan diabetic rats as well as its potential antioxidant activityin vitro.Methods. Albino rats (240–280 g) were given an injection of 120 mg/kg body weight, i.p. of alloxan monohydrate. After 8 days, diabetic animals with elevated fasting blood glucose levels (>9 mmol/L) were considered and selected for the study.Results. Oral treatment with the extract administered every 12 h by gavage at doses of 100, 200, and 400 mg/kg of the extract to the test rats, for 14 days, resulted in a significant dose-dependent decrease in blood glucose levels from 12.82 ± 1.02 mmol/dL to 4.92 ± 2.01 mmol/dL at the highest dose of 400 mg/kg compared to the control drug and glibenclamide as well as attendant significant decline in diabetic rats employed in the study.Conclusion. The extract also showedin vitroconcentration-dependent antioxidant activity following the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and ferric reducing assays. Findings further suggest the presence of active antidiabetic and antioxidant principles inM. oppositifoliusleaves.

Download Full-text