In Vitro and In Vivo Profiles and Characterization of Insulin Nanocarriers Based in Flexible Liposomes Designed for Oral Administration

2019 ◽  
Vol 16 (8) ◽  
pp. 948-960
Author(s):  
Sara Melisa Arciniegas Ruiz ◽  
María Josefa Bernad Bernad ◽  
Raquel Lopez Arellano ◽  
Roberto Diaz Torres ◽  
Sara Del Carmen Caballero Chacón ◽  
...  
Keyword(s):  
Polyacrylamide Gel Electrophoresis ◽  
Oral Route ◽  
Diabetic Rats ◽  
Release Profile ◽  
Therapeutic Effects ◽  
Subcutaneous Route ◽  
In Vivo Test ◽  
Glucose Levels

Background: Alternatives routes of delivery for Insulin have been evaluated to improve treatment for Diabetes Mellitus. The oral route is the most convenient physiologically; it releases in a similar way to endogenous secretion. Flexible liposomes have deformable abilities to pass through membranes with adequate therapeutic effects, but they have been tested only dermally. Objective: Our aim was to develop an oral nanocarrier based on flexible liposomes for insulin with polymer addition to reduce gastrointestinal degradation. Methods: Different percentages of polyethylene glycol were added to a conventional formulation of flexible liposomes. The manufacturing procedure was the heating method. Z potential, size particle, polydispersity index and encapsulation percentage were evaluated. A release profile was performed in the stomach and intestinal pH mediums by two-stage reverse dialysis method. The in-vivo test was performed in experimental diabetic rats by oral, transdermal and subcutaneous routes. Results: All the formulations showed polydispersity but adequate Z potential. The 10% PEG formulation obtained the best insulin enclosure with 81.9%. The insulin integrity after preparation was confirmed by polyacrylamide gel electrophoresis. PEG and non-PEG formulations showed similar behavior in acid release profile but the release and stability of lipid structures were better and longer in intestinal pH conditions. In vivo tests showed a reduction to normal glucose levels only in subcutaneous route. Conclusion: The polymer inclusion in flexible liposomes generates an adequate nanocarrier for proteins in terms of stability and composition; although its in-vivo use reduces glucose levels in subcutaneous route, the effect was not adequate in oral route.

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

2008 ◽  
Vol 5 (4) ◽  
pp. 421-428 ◽  
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.

scholarly journals Ginsenoside Rg1 Alleviates Podocyte Injury Induced by Hyperlipidemia via Targeting the mTOR/NF-κB/NLRP3 Axis

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Tao Wang ◽  
Yanbin Gao ◽  
Rongchuan Yue ◽  
Xiaolei Wang ◽  
Yimin Shi ◽  
...  
Keyword(s):  
Mammalian Target Of Rapamycin ◽  
Diabetic Rats ◽  
Therapeutic Effects ◽  
Ginsenoside Rg1 ◽  
Podocyte Injury ◽  
Therapeutic Function ◽  
Polymerase Chain ◽  
Underlying Mechanisms

Background. Podocyte injury plays an important role in diabetic nephropathy (DN). The aim of this study was to determine the potential therapeutic effects of the ginsenoside Rg1 on hyperlipidemia-stressed podocytes and elucidate the underlying mechanisms. Methods. In vitro and in vivo models of DN were established as previously described, and the expression levels of relevant markers were analyzed by Western blotting, real-time Polymerase Chain Reaction (PCR), immunofluorescence, and immunohistochemistry. Results. Ginsenoside Rg1 alleviated pyroptosis in podocytes cultured under hyperlipidemic conditions, as well as in the renal tissues of diabetic rats, and downregulated the mammalian target of rapamycin (mTOR)/NF-κB pathway. In addition, Rg1 also inhibited hyperlipidemia-induced NLRP3 inflammasome in the podocytes, which was abrogated by the mTOR activator L-leucine (LEU). The antipyroptotic effects of Rg1 manifested as improved renal function in the DN rats. Conclusion. Ginsenoside Rg1 protects podocytes from hyperlipidemia-induced damage by inhibiting pyroptosis through the mTOR/NF-κB/NLRP3 axis, indicating a potential therapeutic function in DN.

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

1990 ◽  
Vol 68 (2) ◽  
pp. 170-173 ◽  
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.

scholarly journals Hypoglycemic Effects of Plant Flavonoids: A Review

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Foo Sok Yen ◽  
Chan Shu Qin ◽  
Sharryl Tan Shi Xuan ◽  
Puah Jia Ying ◽  
Hong Yi Le ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Blood Glucose ◽  
Antioxidant Activities ◽  
Diabetic Rats ◽  
The Body ◽  
High Blood Glucose ◽  
Glucose Levels ◽  
Multiple Organs

Diabetes mellitus is a metabolic disorder with chronic high blood glucose levels, and it is associated with defects in insulin secretion, insulin resistance, or both. It is also a major public issue, affecting the world's population. This disease contributes to long-term health complications such as dysfunction and failure of multiple organs, including nerves, heart, blood vessels, kidneys, and eyes. Flavonoids are phenolic compounds found in nature and usually present as secondary metabolites in plants, vegetables, and fungi. Flavonoids possess many health benefits such as anti-inflammatory and antioxidant activities, and naturally occurring flavonoids contribute to antidiabetic effects.Many studies conducted in vivo and in vitro have proven the hypoglycemic effect of plant flavonoids. A large number of studies showed that flavonoids hold positive results in controlling the blood glucose level in streptozotocin (STZ)-induced diabetic rats and further prevent the complications of diabetes. The future development of flavonoid-based drugs is believed to provide significant effects on diabetes mellitus and diabetes complication diseases. This review aims at summarizing the various types of flavonoids that function as hyperglycemia regulators such as inhibitors of α-glucosidase and glucose cotransporters in the body. This review article discusses the hypoglycemic effects of selected plant flavonoids namely quercetin, kaempferol, rutin, naringenin, fisetin, and morin. Four search engines, PubMed, Google Scholar, Scopus, and SciFinder, are used to collect the data.

Aqueous Extract of Brassica rapa Exerts Antihyperglycemic Activity in Streptozotocin-induced Diabetic Rats

2021 ◽  
Vol 21 ◽  
Author(s):  
Ismail Bouadid ◽  
Ayoub Amssayef ◽  
Nadia Lahrach ◽  
Ahmed El-Haidani ◽  
Mohamed Eddouks
Keyword(s):  
Brassica Rapa ◽  
Aqueous Extract ◽  
Diabetic Rats ◽  
Lipid Profiles ◽  
Antioxidant Effect ◽  
Phytochemical Analysis ◽  
Glucose Levels ◽  
Blood Glucose Levels

Aims: The aim of the study was to assess the antihyperglycemic effect of Brassica rapa. Background: Brassica rapa (turnip) is used as an antidiabetic plant. Objective: This work aimed to evaluate the effect of the aqueous extract of Brassica rapa seeds (AEBRS) on glycemia in vivo. Methods: The effect of AEBRS (60 mg/kg) on glycemia and lipid profiles was evaluated. Besides, preliminary phytochemical analysis and the in vitro antioxidant effect were evaluated. Results: AEBRS caused a significant reduction in blood glucose levels in diabetic rats (p<0.0001). In contrast, no significant effect was observed on lipid profiles, whereas antioxidant potential of this extract has been shown. Phytochemical analysis showed the presence of many important phytochemical families. Conclusion: The present study shows that AEBRS has a potent antihyperglycemic ability in diabetic rats.

Modulation of GLUT4 expression by oral administration of Mg2+ to control sugar levels in STZ-induced diabetic rats

2014 ◽  
Vol 92 (6) ◽  
pp. 438-444 ◽  
Author(s):  
Haniah Solaimani ◽  
Nepton Soltani ◽  
Kianoosh MaleKzadeh ◽  
Shahla Sohrabipour ◽  
Nina Zhang ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Magnesium Sulfate ◽  
Mrna Expression ◽  
Insulin Level ◽  
Diabetic Rats ◽  
In Vivo Studies ◽  
Glucose Levels ◽  
Blood Glucose Levels

It has been previously shown that oral magnesium administration decreases the levels of glucose in the plasma. However, the mechanisms are not fully understood. The aim of this study was to determine the potential role of GLUT4 on plasma glucose levels by orally administering magnesium sulfate to diabetic rats. Animals were distributed among 4 groups (n = 10 rats per group): one group served as the non-diabetic control, while the other groups had diabetes induced by streptozotocin (intraperitoneal (i.p.) injection). The diabetic rats were either given insulin by i.p. injection (2.5 U·(kg body mass)–1·day–1), or magnesium sulfate in their drinking water (10 g·L–1). After 8 weeks of treatment, we conducted an i.p. glucose tolerance test (IPGTT), measured blood glucose and plasma magnesium levels, and performed in-vitro and in-vivo insulin level measurements by radioimmunoassay. Gastrocnemius (leg) muscles were isolated for the measurement of GLU4 mRNA expression using real-time PCR. Administration of magnesium sulfate improved IPGTT and lowered blood glucose levels almost to the normal range. However, the insulin levels were not changed in either of the in-vitro or in-vivo studies. The expression of GLU4 mRNA increased 23% and 10% in diabetic magnesium-treated and insulin-treated groups, respectively. Our findings suggest that magnesium lowers blood glucose levels via increased GLU4 mRNA expression, independent to insulin secretion.

scholarly journals Core structure of flavonoids precursor as an antihyperglycemic and antihyperlipidemic agent: an in vivo study in rats.

2010 ◽  
Vol 57 (4) ◽  
Author(s):  
Mahmoud Najafian ◽  
Azadeh Ebrahim-Habibi ◽  
Parichehreh Yaghmaei ◽  
Kazem Parivar ◽  
Bagher Larijani
Keyword(s):  
Beneficial Effect ◽  
Therapeutic Potential ◽  
Urine Volume ◽  
Diabetic Rats ◽  
Core Structure ◽  
Alpha Amylase ◽  
Glucose Levels ◽  
Blood Glucose Levels

trans-Chalcone is the core structure of naringenin chalcone, located halfway in the biosynthesis pathway of flavonoids. Flavonoids have been reported as mammalian alpha-amylase inhibitors, a property which could be useful in the management of postprandial hyperglycemia in diabetes and related disorders. As a mammalian alpha-amylase inhibitor in vitro, the putative beneficial effect of trans-chalcone on diabetes was tested in a streptozotocin-induced rat model of diabetes type 1, and the results analyzed with commonly used statistical methods. Significant reduction of blood glucose levels and beneficial effect on dyslipidemia were observed in diabetic rats, as well as reduction of disturbing consequences of diabetes such as high urine volume and water intake. trans-chalcone was observed to have a weight loss-inductive effect, alongside with a reduction in food intake, which is suggestive of a therapeutic potential of this compound in overweight and obese patients.

scholarly journals Spironolactone improves nephropathy by enhancing glucose-6-phosphate dehydrogenase activity and reducing oxidative stress in diabetic hypertensive rat

2011 ◽  
Vol 13 (1) ◽  
pp. 56-66 ◽  
Author(s):  
Bruno S Pessôa ◽  
Elisa BMI Peixoto ◽  
Alexandros Papadimitriou ◽  
Jacqueline M Lopes de Faria ◽  
José B Lopes de Faria
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
High Glucose ◽  
Diabetic Rats ◽  
G6pd Activity ◽  
Spontaneously Hypertensive ◽  
Glucose Levels ◽  
Glucose 6 Phosphate Dehydrogenase

Spironolactone (SPR), a mineralocorticoid receptor blocker, diminishes hyperglycemia-induced reduction in glucose-6-phosphate dehydrogenase (G6PD) activity, improving oxidative stress damage. This study investigated whether SPR ameliorates nephropathy by increasing G6PD activity and reducing oxidative stress in spontaneously hypertensive diabetic rats (SHRs). The streptozotocin-induced diabetic rats received or not SPR 50 mg/kg per day, for eight weeks. A human mesangial cell line was cultured in normal or high glucose conditions, with or without SPR, for 24 h. Plasma glucose levels and systolic blood pressure were unaltered by diabetes or by SPR treatment. Albuminuria, fibronectin expression, 8-OHdG urinary levels, lipid peroxidation and p47phox expression were higher in the diabetic rats compared with the control and were reduced by SPR. The antioxidant GSH/GSSG ratio was reduced in the diabetic rats and the treatment reestablished it. Diabetes-induced SGK1 up-regulation was inhibited by SPR. Reactive oxygen species (ROS) and superoxide production induced by NADPH oxidase were increased by hyperglycemia and high glucose, in vivo and in vitro, respectively, and were reduced with SPR. Hyperglycemia and high glucose decreased G6PD activity, which was restored with SPR. These results suggest that SPR ameliorates nephropathy in diabetic SHRs by restoring G6PD activity and diminishes oxidative stress without affecting glycaemia and blood pressure.

scholarly journals Optimization of Thiolated Chitosan Nanoparticles for the Enhancement of in Vivo Hypoglycemic Efficacy of Sitagliptin in Streptozotocin-Induced Diabetic Rats

Pharmaceutics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 300 ◽  
Author(s):  
Kousalya Prabahar ◽  
Ubaidulla Udhumansha ◽  
Mona Qushawy
Keyword(s):  
Drug Release ◽  
Chitosan Nanoparticles ◽  
Crosslinking Agent ◽  
Entrapment Efficiency ◽  
Diabetic Rats ◽  
Thiolated Chitosan ◽  
Diabetes Mellitus Type Ii ◽  
Glucose Levels

Sitagliptin (SGN) is an antidiabetic drug used for treatment of diabetes mellitus type II. The objectives of this study were to formulate SGN in form of thiolated chitosan (TC) nanoparticles to enhance the mucoadhesion properties of SGN to the gastrointestinal tract, prolong drug release, decrease side effects, and enhance patient compliance. Seventeen batches of SGN-TC nanoparticles were designed by Box-Behnken design and prepared using the ionic gelation method using tripolyphosphate (TPP) as crosslinking agent. The prepared formulations were evaluated for particle size, entrapment efficiency %, and in vitro drug release. Based on the results of optimization, three formulations (F1–F3) were prepared with different drug polymer ratios (1:1, 1:2, and 1:3). The mucoadhesion study and in vivo hypoglycemic activity of three formulations were evaluated in comparison to free SGN in streptozotocin (STZ)-induced diabetic rats. The seventeen SGN-TC nanoparticles showed small particle sizes, high entrapment efficiency, and prolonged drug release. The concentration of TC polymers had highest effect on these responses. The percentage of SGN–TC nanoparticles adhered to tissue was increased and the release was prolonged as the concentration of TC polymer increased (F3 > F2 > F1). The hypoglycemic effect of SGN-TC nanoparticles was significantly higher than resulted by free SGN. It was concluded that TC nanoparticles had the ability to enhance the mucoadhesion properties of SGN and prolong the drug release. SGN-TC nanoparticles significantly reduced plasma glucose levels compared to free SGN in STZ-induced diabetic rats.

Normal Ca2+ extrusion by the Ca2+ pump of intact red blood cells exposed to high glucose concentrations

2001 ◽  
Vol 280 (6) ◽  
pp. C1449-C1454 ◽  
Author(s):  
Julia E. Raftos ◽  
Amanda Edgley ◽  
Robert M. Bookchin ◽  
Zipora Etzion ◽  
Virgilio L. Lew ◽  
...  
Keyword(s):  
High Glucose ◽  
Diabetic Rats ◽  
Maximal Velocity ◽  
Glucose Levels ◽  
Normal Human ◽  
Streptozotocin Diabetic Rats ◽  
The Mean ◽  
Human Rbcs

The ATPase activity of the plasma membrane Ca2+ pump (PMCA) has been reported to be inhibited by exposure of red blood cell (RBC) PMCA preparations to high glucose concentrations. It has been claimed that this effect could have potential pathophysiological relevance in diabetes. To ascertain whether high glucose levels also affect PMCA transport function in intact RBCs, Ca2+extrusion by the Ca2+-saturated pump [PMCA maximal velocity ( V max)] was measured in human and rat RBCs exposed to high glucose in vivo or in vitro. Preincubation of normal human RBCs in 30–100 mM glucose for up to 6 h had no effect on PMCA V max. The mean V max of RBCs from 15 diabetic subjects of 12.9 ± 0.7 mmol · 340 g Hb−1 · h−1 was not significantly different from that of controls (14.3 ± 0.5 mmol · 340 g Hb−1 · h−1). Similarly, the PMCA V max of RBCs from 11 streptozotocin-diabetic rats was not affected by plasma glucose levels more than three times normal for 6–8 wk. Thus exposure to high glucose concentrations does not affect the ability of intact RBCs to extrude Ca2+.

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