scholarly journals Glucose lowering by SGLT2-inhibitor empagliflozin accelerates atherosclerosis regression in hyperglycemic STZ-diabetic mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jan Pennig ◽  
Philipp Scherrer ◽  
Mark Colin Gissler ◽  
Nathaly Anto-Michel ◽  
Natalie Hoppe ◽  
...  
Keyword(s):  
Leukocyte Adhesion ◽  
Plasma Cholesterol ◽  
Sglt2 Inhibitor ◽  
Vascular Wall ◽  
High Cholesterol Diet ◽  
Chow Diet ◽  
Diabetic Mice ◽  
Glucose Lowering ◽  
Atherosclerosis Progression ◽  
Glucose Levels

AbstractDiabetes worsens atherosclerosis progression and leads to a defect in repair of arteries after cholesterol reduction, a process termed regression. Empagliflozin reduces blood glucose levels via inhibition of the sodium glucose cotransporter 2 (SGLT-2) in the kidney and has been shown to lead to a marked reduction in cardiovascular events in humans. To determine whether glucose lowering by empagliflozin accelerates atherosclerosis regression in a mouse model, male C57BL/6J mice were treated intraperitoneally with LDLR- and SRB1- antisense oligonucleotides and fed a high cholesterol diet for 16 weeks to induce severe hypercholesterolemia and atherosclerosis progression. At week 14 all mice were rendered diabetic by streptozotocin (STZ) injections. At week 16 a baseline group was sacrificed and displayed substantial atherosclerosis of the aortic root. In the remaining mice, plasma cholesterol was lowered by switching to chow diet and treatment with LDLR sense oligonucleotides to induce atherosclerosis regression. These mice then received either empagliflozin or vehicle for three weeks. Atherosclerotic plaques in the empagliflozin treated mice were significantly smaller, showed decreased lipid and CD68+ macrophage content, as well as greater collagen content. Proliferation of plaque resident macrophages and leukocyte adhesion to the vascular wall were significantly decreased in empagliflozin-treated mice. In summary, plasma glucose lowering by empagliflozin improves plaque regression in diabetic mice.

scholarly journals Atherosclerosis Development and Aortic Contractility in Hypercholesterolemic Rabbits Supplemented with Two Different Flaxseed Varieties

Foods ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 534
Author(s):  
Jolanta Bujok ◽  
Dorota Miśta ◽  
Edyta Wincewicz ◽  
Bożena Króliczewska ◽  
Stanisław Dzimira ◽  
...  
Keyword(s):  
Vascular Reactivity ◽  
Plasma Cholesterol ◽  
Basal Diet ◽  
Vascular Wall ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Alpha Linolenic Acid ◽  
High Concentration ◽  
Atherosclerosis Progression

Alpha-linolenic acid (ALA) is widely regarded as the main beneficial component of flax for the prevention of cardiovascular disease. We evaluated the effect of the transgenic flaxseed W86—which is rich in ALA—on the lipid profile, atherosclerosis progression, and vascular reactivity in hypercholesterolemic rabbits compared to the parental cultivar Linola with a very low ALA content. Rabbits were fed a basal diet (control) or a basal diet supplemented with 1% cholesterol, 1% cholesterol and 10% flaxseed W86, or 1% cholesterol and 10% Linola flaxseed. A high-cholesterol diet resulted in an elevated plasma cholesterol and triglyceride levels compared to the control animals. Aortic sections from rabbits fed Linola had lower deposits of foamy cells than those from rabbits fed W86. A potassium-induced and phenylephrine-induced contractile response was enhanced by a high-cholesterol diet and not influenced by the W86 or Linola flaxseed. Pretreatment of the aortic rings with nitro-L-arginine methyl ester resulted in a concentration-dependent tendency to increase the reaction amplitude in the control and high-cholesterol diet groups but not the flaxseed groups. Linola flaxseed with a low ALA content more effectively reduced the atherosclerosis progression compared with the W86 flaxseed with a high concentration of stable ALA. Aorta contractility studies suggested that flaxseed ameliorated an increased contractility in hypercholesterolemia but had little or no impact on NO synthesis in the vascular wall.

scholarly journals Leptin contributes to the beneficial effects of insulin treatment in streptozotocin-diabetic male mice

2018 ◽  
Vol 315 (6) ◽  
pp. E1264-E1273
Author(s):  
Ursula H. Neumann ◽  
Michelle M. Kwon ◽  
Robert K. Baker ◽  
Timothy J. Kieffer
Keyword(s):  
Blood Glucose ◽  
Insulin Therapy ◽  
Daily Injection ◽  
Diabetic Mice ◽  
Glucose Lowering ◽  
Beneficial Effects ◽  
Glucose Levels ◽  
Lowering Effect ◽  
Blood Glucose Levels ◽  
Glucose Lowering Effect

It was long thought that the only hormone capable of reversing the catabolic consequences of diabetes was insulin. However, various studies have demonstrated that the adipocyte-derived hormone leptin can robustly lower blood glucose levels in rodent models of insulin-deficient diabetes. In addition, it has been suggested that some of the metabolic manifestations of insulin-deficient diabetes are due to hypoleptinemia as opposed to hypoinsulinemia. Because insulin therapy increases leptin levels, we sought to investigate the contribution of leptin to the beneficial effects of insulin therapy. To do this, we tested insulin therapy in streptozotocin (STZ) diabetic mice that were either on an ob/ ob background or that were given a leptin antagonist to determine if blocking leptin action would blunt the glucose-lowering effects of insulin therapy. We found that STZ diabetic ob/ ob mice have a diminished blood glucose-lowering effect in response to insulin therapy compared with STZ diabetic controls and exhibited more severe weight loss post-STZ injection. In addition, STZ diabetic mice administered a leptin antagonist through daily injection or plasmid expression respond less robustly to insulin therapy as assessed by both fasting blood glucose levels and blood glucose levels during an oral glucose tolerance test. However, leptin antagonism did not prevent the insulin-induced reduction in β-hydroxybutyrate and triglyceride levels. Therefore, we conclude that elevated leptin levels can contribute to the glucose-lowering effect of insulin therapy in insulin-deficient diabetes.

Fasting is not required for measuring plasma lipid levels in rabbits

2019 ◽  
Vol 54 (3) ◽  
pp. 272-280 ◽  
Author(s):  
Rong Wang ◽  
Ruihan Liu ◽  
Lu Li ◽  
Baoning Liu ◽  
Liang Bai ◽  
...  
Keyword(s):  
Corn Oil ◽  
Experimental Studies ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Diet Group ◽  
Lipoprotein Cholesterol ◽  
High Cholesterol Diet ◽  
Chow Diet ◽  
Lipid Levels ◽  
Glucose Levels

Plasma lipid and glucose levels are important parameters for evaluating the onset and development of metabolic and cardiovascular diseases. In clinical and experimental studies of humans or mice, fasting is often required before testing plasma lipid and glucose levels. The rabbit is a valuable animal model for cardiovascular disease research. However, whether fasting is necessary for measuring plasma lipid and glucose levels in rabbits remains unclear. In the current study, 12 healthy Japanese white rabbits (males weighing 2.5–3.0 kg) were randomly divided into a chow diet group ( n = 6) and a high cholesterol diet group ( n = 6). They were fed either a standard chow diet or a chow diet supplemented with 0.5% cholesterol and 3% corn oil for 12 weeks. After 12 weeks, the plasma levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and glucose were measured before and after various fasting durations (8, 12, 16, 20 and 24 h). The results showed that there were no significant differences in lipid levels between the fasting and non-fasting samples, whereas glucose levels were lower after 8 h of fasting than in the absence of fasting. Moreover, the glucose levels were restored to normal after 8 h of refeeding. These results indicate that fasting does not affect plasma lipid values in rabbits but that fasting is important for determining the glucose level in rabbits. These findings may be helpful for future rabbit experiments and beneficial for animal welfare.

scholarly journals Drug-Herb Interaction between Metformin and Momordica charantia in Diabetic Mice

2019 ◽  
Vol 3 (2) ◽  
pp. 81
Author(s):  
Asri Dwi Endah Dewi Pramesthi ◽  
Mirhansyah Ardana ◽  
Niken Indriyanti
Keyword(s):  
Fruit Juice ◽  
Negative Control ◽  
Momordica Charantia ◽  
Bitter Gourd ◽  
Diabetic Mice ◽  
Once Daily ◽  
Glucose Lowering ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Significant Difference

Background: Bitter gourd has various metabolites, such as momordicosides, polypeptide-P, v-insulin, charantin, and vicine that have antidiabetic effect. It has synergistically effect while combined with oral diabetic drugs, such as metformin as glucose lowering agent. The aim of this study is to investigate the interaction of bitter gourd fruit juice and metformin as glucose lowering agent in mice.Materials and Methods: Alloxan-induced diabetic mice were treated with bitter gourd fruit juice, metformin, and the combination of those two for 21 days. Glucose level was checked on first and last day of treatment.Results: Furthermore, blood glucose levels measurement showed no significant difference between groups compared with negative control, which was p>0.05. The stomach of groups that treated with metformin and bitter gourd fruit juice histopathologically showed no significant differences.Conclusion: The use of bitter gourd once daily together with metformin is a better choice, while twice daily might induce hypoglycemia and mice death. There is no interaction between them on lowering blood glucose.Keywords: metformin, Momordica charantia, diabetes mellitus

scholarly journals Berberine decreases plasma triglyceride levels and upregulates hepatic TRIB1 in LDLR wild type mice and in LDLR deficient mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Amar Bahadur Singh ◽  
Jingwen Liu
Keyword(s):  
Mrna Expression ◽  
Plasma Cholesterol ◽  
Lipid Lowering ◽  
High Cholesterol Diet ◽  
Chow Diet ◽  
Mrna Levels ◽  
New Findings ◽  
Deficient Mice

Abstract TRIB1 is a GWAS locus associated with plasma cholesterol and triglycerides (TG) levels. In mice, liver-specific overexpression of TRIB1 lowers plasma lipid levels. Berberine (BBR) is a natural lipid lowering drug that reduces plasma LDL-cholesterol (LDL-C), total cholesterol (TC) and TG in hyperlipidemic patients and in mice by mechanisms involving upregulation of hepatic LDL receptor (LDLR). Here, we demonstrated that BBR treatment reduced plasma LDL-C, TC and TG in LDLR wildtype (WT) mice fed a high fat and high cholesterol diet and it only lowered TG in LDLR WT mice fed a normal chow diet. In hypercholesterolemic LDLR deficient mice (Ldlr−/−), BBR treatment reduced plasma TG levels by 51% compared to the vehicle control without affecting plasma cholesterol levels. Hepatic gene expression analysis revealed that Trib1 mRNA levels were significantly elevated by BBR treatment in all three mouse models and increases of Trib1 mRNA expression were associated with reduced expression of lipogenic genes including Cebpa, Acc1 and Scd1. In vitro studies further demonstrate that BBR induces TRIB1 mRNA expression by a transcriptional mechanism via ERK signaling pathway. These new findings warrant future in vivo studies to determine the causal role of Trib1 in BBR-mediated TG lowering independent of LDLR regulation.

Effects of krill oil intake on plasma cholesterol and glucose levels in rats fed a high-cholesterol diet

2013 ◽  
Vol 93 (11) ◽  
pp. 2669-2675 ◽  
Author(s):  
Dong-Mei Li ◽  
Da-Yong Zhou ◽  
Bei-Wei Zhu ◽  
Ya-Li Chi ◽  
Li-Ming Sun ◽  
...  
Keyword(s):  
Plasma Cholesterol ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
Krill Oil ◽  
High Cholesterol ◽  
Glucose Levels

Evaluation of Glucose and Lipid Lowering Activity of Arganimide A in Normal and Streptozotocin-Induced Diabetic Rats

2019 ◽  
Vol 19 (4) ◽  
pp. 503-510 ◽  
Author(s):  
Mohamed Eddouks ◽  
Farid Khallouki ◽  
Robert W. Owen ◽  
Morad Hebi ◽  
Remy Burcelin
Keyword(s):  
Body Weight ◽  
Blood Glucose ◽  
Oral Administration ◽  
Lipid Profile ◽  
Plasma Cholesterol ◽  
Diabetic Rats ◽  
Lipid Lowering ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Lowering Activity

Aims: Arganimide A (4,4-dihydroxy-3,3-imino-di-benzoic acid) is a compound belonging to a family of aminophenolics found in fruit of Argania spinosa. The purpose of this study was to investigate the glucose and lipid lowering activity of Arganimide A (ARG A). Methods: The effect of a single dose and daily oral administration of Arganimide A (ARG A) on blood glucose levels and plasma lipid profile was tested in normal and streptozotocin (STZ) diabetic rats at a dose of 2 mg/kg body weight. Results: Single oral administration of ARG A reduced blood glucose levels from 26.50±0.61 mmol/L to 14.27±0.73 mmol/L (p<0.0001) six hours after administration in STZ diabetic rats. Furthermore, blood glucose levels were decreased from 5.35±0.30 mmol/L to 3.57±0.17 mmol/L (p<0.0001) and from 26.50±0.61 mmol/L to 3.67±0.29 mmol/L (p<0.0001) in normal and STZ diabetic rats, respectively, after seven days of treatment. Moreover, no significant changes in body weight in normal and STZ rats were shown. According to the lipid profile, the plasma triglycerides levels were decreased significantly in diabetic rats after seven days of ARG treatment (p<0.05). Moreover, seven days of ARG A treatment decreased significantly the plasma cholesterol concentrations (p<0.001). Conclusion: ARG A possesses glucose and lipid-lowering activity in diabetic rats and this natural compound may be beneficial in the treatment of diabetes.

Deficiency of endothelial CD40 induces a stable plaque phenotype and limits inflammatory cell recruitment to atherosclerotic lesions in mice

2021 ◽  
Author(s):  
Mark Colin Gissler ◽  
Philipp Scherrer ◽  
Nathaly Anto Michel ◽  
Jan Pennig ◽  
Natalie Hoppe ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Inflammatory Cell ◽  
Leukocyte Adhesion ◽  
Critical Role ◽  
Atherosclerotic Lesion ◽  
Intercellular Adhesion Molecule ◽  
Atherosclerotic Plaques ◽  
Chow Diet ◽  
Stable Plaque ◽  
Plaque Phenotype

Objectives: The co-stimulatory CD40L-CD40 dyad exerts a critical role in atherosclerosis by modulating leukocyte accumulation into developing atherosclerotic plaques. The requirement for cell-type specific expression of both molecules, however, remains elusive. Here, we evaluate the contribution of CD40 expressed on endothelial cells (ECs) in a mouse model of atherosclerosis. Approach & Results: Atherosclerotic plaques of Apolipoprotein E deficient (Apoe-/-) mice and humans displayed increased expression of CD40 on ECs compared to controls. To interrogate the role of CD40 on ECs in atherosclerosis, we induced EC-specific (BmxCreERT2-driven) deficiency of CD40 in Apoe-/- mice. After feeding a chow diet for 25 weeks, EC-specific deletion of CD40 (iEC-CD40) ameliorated plaque lipid deposition and lesional macrophage accumulation but increased intimal smooth muscle cell and collagen content, while atherosclerotic lesion size did not change. Leukocyte adhesion to the vessel wall was impaired in iEC-CD40-deficient mice as demonstrated by intravital microscopy. In accord, expression of vascular adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 in the vascular endothelium declined after deletion of CD40. In vitro, antibody-mediated inhibition of human endothelial CD40 significantly abated monocyte adhesion on ECs. Conclusions: Endothelial deficiency of CD40 in mice promotes structural features associated with a stable plaque phenotype in humans and decreases leukocyte adhesion. These results suggest that endothelial-expressed CD40 contributes to inflammatory cell migration and consecutive plaque formation in atherogenesis.

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