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.

Abstract 606: Impaired Glucose Metabolism in the Triggering Receptor Expressed in Myeloid Cells Like Transcript- 1 Null Mice A Link to Obesity

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Elizabeth Castro Rivera ◽  
Abdías Díaz Rosado ◽  
Anthony V Washington
Keyword(s):  
Serum Insulin ◽  
Insulin Response ◽  
Myeloid Cells ◽  
Tolerance Test ◽  
Similar Response ◽  
Fatty Acid Production ◽  
Glucose Levels ◽  
Significant Difference

Fat rich foods have been shown to produce increased body weight and diabetes in various strains of mice. When fed ad libitum with a high fat diet (HFD), apolipoprotein E deficient ( apoe -/- ) mice develop hypercholesterolemia, but are not known to be obese. Our laboratory demonstrated that the triggering receptor expressed in myeloid cells (TREM) like transcript-1 (TLT-1), as a potential target for intervention during atherosclerosis, diabetes, and obesity. Crossing the treml1 -/- mouse onto an apoe -/- background (DKO), we found DKO mice had smaller lesions than apoe -/- mice, yet had significantly higher triglycerides and weight gain over a 20-week period of HFD. Further investigation demonstrated treml1 -/- mice to have higher cholesterol than wild type mice (wt), suggesting the treml1 mutation contributes to the phenotype observed in DKO mice. Glucose evaluation of treml1 -/- , treml1 +/- and wt mice, showed a significant difference in basal glucose, and in plasma glucose clearance, as revealed by intraperitoneal (IP) glucose tolerance test. Analysis of serum insulin by ELISA showed no differences, while IP insulin tolerance test revealed treml1 -/- and treml1 +/- mice present apparent insulin hypersensitivity, as represented by the steady glucose decline 15 min post injection, with no recovery after two hours. Western blot performed in various tissues, demonstrated the presence of a TLT-1 splice variant that lacks the extracellular domain (TLT-1s), in the adipose tissue of treml1 -/- but not wt mice. Analysis of insulin response, in vivo by insulin sensitivity assay and in vitro using TSA 201 cells transfected with TLT-1s to determine the effect on AKT activation, revealed enhanced phosphorylation in the presence of TLT-1, with a similar response observed in vitro. This data support a model where TLT-1s modulation of AKT phosphorylation, increases adipocyte glucose uptake, leading to: low blood glucose levels, increased fatty acid production and storage, and the obese phenotype we observed in our mice.

Incretin release from gut is acutely enhanced by sugar but not by sweeteners in vivo

2009 ◽  
Vol 296 (3) ◽  
pp. E473-E479 ◽  
Author(s):  
Yukihiro Fujita ◽  
Rhonda D. Wideman ◽  
Madeleine Speck ◽  
Ali Asadi ◽  
David S. King ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Sweet Taste ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Dependent Manner ◽  
Glucose Levels ◽  
Zucker Diabetic Fatty Rats ◽  
Glucagon Like Peptide 1

Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are released during meals from endocrine cells located in the gut mucosa and stimulate insulin secretion from pancreatic β-cells in a glucose-dependent manner. Although the gut epithelium senses luminal sugars, the mechanism of sugar sensing and its downstream events coupled to the release of the incretin hormones are not clearly elucidated. Recently, it was reported that sucralose, a sweetener that activates the sweet receptors of taste buds, triggers incretin release from a murine enteroendocrine cell line in vitro. We confirmed that immunoreactivity of α-gustducin, a key G-coupled protein involved in taste sensing, is sometimes colocalized with GIP in rat duodenum. We investigated whether secretion of incretins in response to carbohydrates is mediated via taste receptors by feeding rats the sweet-tasting compounds saccharin, acesulfame potassium, d-tryptophan, sucralose, or stevia. Oral gavage of these sweeteners did not reduce the blood glucose excursion to a subsequent intraperitoneal glucose tolerance test. Neither oral sucralose nor oral stevia reduced blood glucose levels in Zucker diabetic fatty rats. Finally, whereas oral glucose increased plasma GIP levels ∼4-fold and GLP-1 levels ∼2.5-fold postadministration, none of the sweeteners tested significantly increased levels of these incretins. Collectively, our findings do not support the concept that release of incretins from enteroendocrine cells is triggered by carbohydrates via a pathway identical to the sensation of “sweet taste” in the tongue.

scholarly journals CYP2J2 attenuates metabolic dysfunction in diabetic mice by reducing hepatic inflammation via the PPARγ

2015 ◽  
Vol 308 (4) ◽  
pp. E270-E282 ◽  
Author(s):  
Rui Li ◽  
Xizhen Xu ◽  
Chen Chen ◽  
Yan Wang ◽  
Artiom Gruzdev ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Biological Effects ◽  
Tolerance Test ◽  
Mapk Signaling ◽  
Metabolic Dysfunction ◽  
Glucose Levels ◽  
Hepatic Cells ◽  
Insulin Tolerance

Epoxyeicosatrienoic acids (EETs) and arachidonic acid-derived cytochrome P450 (CYP) epoxygenase metabolites have diverse biological effects, including anti-inflammatory properties in the vasculature. Increasing evidence suggests that inflammation in type 2 diabetes is a key component in the development of insulin resistance. In this study, we investigated whether CYP epoxygenase expression and exogenous EETs can attenuate insulin resistance in diabetic db/db mice and in cultured hepatic cells (HepG2). In vivo, CYP2J2 expression and the accompanying increase in EETs attenuated insulin resistance, as determined by plasma glucose levels, glucose tolerance test, insulin tolerance test, and hyperinsulinemic euglycemic clamp studies. CYP2J2 expression reduced the production of proinflammatory cytokines in liver, including CRP, IL-6, IL-1β, and TNFα, and decreased the infiltration of macrophages in liver. CYP2J2 expression also decreased activation of proinflammatory signaling cascades by decreasing NF-κB and MAPK activation in hepatocytes. Interestingly, CYP2J2 expression and exogenous EET treatment increased glucose uptake and activated the insulin-signaling cascade both in vivo and in vitro, suggesting that CYP2J2 metabolites play a role in glucose homeostasis. Furthermore, CYP2J2 expression upregulated PPARγ, which has been shown to induce adipogenesis, which attenuates dyslipidemias observed in diabetes. All of the findings suggest that CYP2J2 expression attenuates the diabetic phenotype and insulin resistance via inhibition of NF-κB and MAPK signaling pathways and activation of PPARγ.

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.

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 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 In Vitro and In Vivo Effects of Norathyriol and Mangiferin on α-Glucosidase

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Zhi-Long Shi ◽  
Yi-Dan Liu ◽  
Yun-Yun Yuan ◽  
Da Song ◽  
Mei-Feng Qi ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Glucose Tolerance Test ◽  
Fasting Blood Glucose ◽  
Tolerance Test ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
In Vivo Effects ◽  
Antidiabetic Effects

Norathyriol is a metabolite of mangiferin. Mangiferin has been reported to inhibit α-glucosidase. To the best of our knowledge, no study has been conducted to determine or compare those two compounds on inhibiting α-glucosidase in vitro and in vivo by far. In this study, we determined the inhibitory activity of norathyriol and mangiferin on α-glucosidase in vitro and evaluated their antidiabetic effect in diabetic mice. The results showed that norathyriol inhibited α-glucosidase in a noncompetitive manner with an IC50 value of 3.12 μM, which is more potent than mangiferin (IC50 = 358.54 μM) and positive drug acarbose (IC50 = 479.2 μM) in the zymological experiment. Both of norathyriol and mangiferin caused significant (p<0.05) reduction in fasting blood glucose and the blood glucose levels at two hours after carbohydrate loading and it was interesting that mangiferin and norathyriol can make the decline of the blood glucose earlier than other groups ever including normal group in the starch tolerance test. However, norathyriol and mangiferin did not significantly influence carbohydrate absorption in the glucose tolerance test. Therefore, the antidiabetic effects of norathyriol and mangiferin might be associated with α-glucosidase, and norathyriol was more potent than mangiferin.

scholarly journals Synthesis and In Vitro AMPK Activation of Cycloalkyl/Alkarylbiguanides with Robust In Vivo Antihyperglycemic Action

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Erika Gutierrez-Lara ◽  
Carlos Martínez-Conde ◽  
Edgar Rosales-Ortega ◽  
Juan José Ramírez-Espinosa ◽  
Julio C. Rivera-Leyva ◽  
...  
Keyword(s):  
Binding Pocket ◽  
Tolerance Test ◽  
Regulatory Subunit ◽  
Oral Glucose ◽  
Alkyl Aryl ◽  
Design Synthesis ◽  
Glucose Levels ◽  
Amp Activated Protein Kinase

This work describes the design, synthesis in one step, and the in vitro, in vivo, and in silico antidiabetic evaluation of a series of ten alicyclic and aromatic (alkyl +aryl: alkaryl)biguanides, analogues of metformin and phenformin. The design was conceived using isosteric replacement, chain-ring transformation, and lower and higher homologation strategies. All compounds were obtained as crystals and their structure was confirmed on the basis of their spectral data (NMR and mass spectra), and their purity was ascertained by microanalysis. Compounds were in vitro evaluated as activators of AMP-Activated Protein Kinase (AMPK). The results indicated that compounds 4, 5, and 6 showed similar or even better effect compared to metformin. Docking analysis was performed with regulatory subunit γ of AMPK, showing several interactions with nucleotide binding pocket. The in vivo evaluation of compounds 4–6 at a single dose of 50 mg/kg was performed in a murine experimental model of diabetes. The results showed an important and robust decrease of plasmatic glucose levels (−40%). Compound 6 was selected for an oral glucose tolerance test, showing an antihyperglycemic effect similar to metformin. The in vivo results indicated that compounds 4–6 may be effective in treating experimental T2DM.

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