scholarly journals Increased Inflammation in Atherosclerotic Lesions of DiabeticAkita-LDLr−/−Mice Compared to NondiabeticLDLr−/−Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Daniel Engelbertsen ◽  
Fong To ◽  
Pontus Dunér ◽  
Olga Kotova ◽  
Ingrid Söderberg ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Plasma Cholesterol ◽  
Microvascular Complications ◽  
Fold Increase ◽  
Inflammatory Cells ◽  
Glucose Levels ◽  
Atherosclerotic Lesions ◽  
Blood Glucose Levels ◽  
Plaque Inflammation

Background. Diabetes is associated with increased cardiovascular disease, but the underlying cellular and molecular mechanisms are poorly understood. One proposed mechanism is that diabetes aggravates atherosclerosis by enhancing plaque inflammation. TheAkitamouse has recently been adopted as a relevant model for microvascular complications of diabetes. Here we investigate the development of atherosclerosis and inflammation in vessels ofAkitamice onLDLr−/−background.Methods and Results.Akita-LDLr−/−andLDLr−/−mice were fed high-fat diet from 6 to 24 weeks of age. Blood glucose levels were higher in both male and femaleAkita-LDLr−/−mice (137% and 70%, resp.). MaleAkita-LDLr−/−mice had markedly increased plasma cholesterol and triglyceride levels, a three-fold increase in atherosclerosis, and enhanced accumulation of macrophages and T-cells in plaques. In contrast, femaleAkita-LDLr−/−mice demonstrated a modest 29% increase in plasma cholesterol and no significant increase in triglycerides, atherosclerosis, or inflammatory cells in lesions. MaleAkita-LDLr−/−mice had increased levels of plasma IL-1βcompared to nondiabetic mice, whereas no such difference was seen between female diabetic and nondiabetic mice.Conclusion.Akita-LDLr−/−mice display considerable gender differences in the development of diabetic atherosclerosis. In addition, the increased atherosclerosis in maleAkita-LDLr−/−mice is associated with an increase in inflammatory cells in lesions.

Effects of Maternal Flaxseed Supplementation on Female Offspring of Diabetic Rats in Serum Concentration of Glucose, Insulin, and Thyroid Hormones

2019 ◽  
Vol 89 (1-2) ◽  
pp. 45-54
Author(s):  
Akemi Suzuki ◽  
André Manoel Correia-Santos ◽  
Gabriela Câmara Vicente ◽  
Luiz Guillermo Coca Velarde ◽  
Gilson Teles Boaventura
Keyword(s):  
Thyroid Hormones ◽  
High Fat Diet ◽  
Female Offspring ◽  
Flaxseed Oil ◽  
Diabetic Rats ◽  
High Fat ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Flaxseed Flour ◽  
Maternal Consumption

Abstract. Objective: This study aimed to evaluate the effect of maternal consumption of flaxseed flour and oil on serum concentrations of glucose, insulin, and thyroid hormones of the adult female offspring of diabetic rats. Methods: Wistar rats were induced to diabetes by a high-fat diet (60%) and streptozotocin (35 mg/kg). Rats were mated and once pregnancy was confirmed, were divided into the following groups: Control Group (CG): casein-based diet; High-fat Group (HG): high-fat diet (49%); High-fat Flaxseed Group (HFG): high-fat diet supplemented with 25% flaxseed flour; High-fat Flaxseed Oil group (HOG): high-fat diet, where soya oil was replaced with flaxseed oil. After weaning, female pups (n = 6) from each group were separated, received a commercial rat diet and were sacrificed after 180 days. Serum insulin concentrations were determined by ELISA, the levels of triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH) were determined by chemiluminescence. Results: There was a significant reduction in body weight at weaning in HG (−31%), HFG (−33%) and HOG (44%) compared to CG (p = 0.002), which became similar by the end of 180 days. Blood glucose levels were reduced in HFG (−10%, p = 0.044) when compared to CG, and there was no significant difference between groups in relation to insulin, T3, T4, and TSH after 180 days. Conclusions: Maternal severe hyperglycemia during pregnancy and lactation resulted in a microsomal offspring. Maternal consumption of flaxseed reduces blood glucose levels in adult offspring without significant effects on insulin levels and thyroid hormones.

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.

scholarly journals Effects of Indian Gooseberry Fruit on Anxiety-Related Behaviors and Memory Performance in High-fat Diet-induced Obese Mice

2021 ◽  
Vol 20 (4) ◽  
Author(s):  
Sirikran Juntapremjit ◽  
◽  
Yoottana Janthakhin ◽  
Keyword(s):  
High Fat Diet ◽  
Fruit Juice ◽  
Memory Performance ◽  
Normal Diet ◽  
Obese Mice ◽  
High Fat ◽  
Glucose Levels ◽  
Indian Gooseberry ◽  
Blood Glucose Levels ◽  
Diet Control

Abstract Indian gooseberry (Phyllanthus emblica L.) is widely used in Ayurvedic medicine, traditional Chinese medicine, as well as traditional medicine to treat health complications including disorders of diabetes and obesity. The aim of this study was to investigate the effects of Indian gooseberry fruit on anxiety-related behaviors and memory performance in high-fat diet-induced obese mice. C57BL/6 mice were randomly divided into four groups (n = 11 pre group); group 1: normal diet control, 2: normal diet treated with Indian gooseberry fruit juice, 3: high-fat diet control, and 4: high-fat diet treated with Indian gooseberry fruit juice. Each mouse was orally and daily administrated with 5mL/kg of Indian gooseberry fruit juice. After six weeks, all groups were tested for blood glucose levels, anxiety and memory performances, and the level of interleukin 6 (IL-6) in the hippocampus. The results revealed that the treatment with Indian gooseberry juice for six weeks produced a significant decrease in blood glucose levels (P <0.05). In anxiety-related behaviors, Indian gooseberry juice showed a remarkable decrease in self-grooming behavior (P <0.001). In addition, there was a significant increase in memory performance in the high-fat diet treated with Indian gooseberry fruit juice compared to the high-fat diet control (P <0.05). Furthermore, the level of inflammatory cytokine IL-6 in the hippocampus was significantly decreased after oral administration of Indian gooseberry fruit juice (P <0.05). These findings suggest that Indian gooseberry fruit can serve as a natural nutritional treatment for preventing high-fat diet-induced cognitive impairment. Keywords: Anxiety-related behaviors, High-fat diet, Indian gooseberry, Memory performance, Obesity

scholarly journals Hydroxytyrosol Plays Antiatherosclerotic Effects through Regulating Lipid Metabolism via Inhibiting the p38 Signal Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Xinxin Zhang ◽  
Yating Qin ◽  
Xiaoning Wan ◽  
Hao Liu ◽  
Chao Iv ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Molecular Mechanisms ◽  
Cholesterol Metabolism ◽  
Fold Increase ◽  
Heart Tissue ◽  
Control Group ◽  
Atherosclerotic Lesions ◽  
Serum Crp

Purpose. Hydroxytyrosol (HT) processes multiaspect pharmacological properties such as antithrombosis and antidiabetes. The aim of this study was to explore the antistherosclerotic roles and relevant mechanisms of HT. Methods. Male apoE-/- mice were randomly divided into 2 groups: the control group and the HT group (10 mg/kg/day orally). After 16 weeks, blood tissue, heart tissue, and liver tissue were obtained to detect the atherosclerotic lesions, histological analysis, lipid parameters, and inflammation. And the underlying molecular mechanisms of HT were also studied in vivo and in vitro. Results. HT administration significantly reduced the extent of atherosclerotic lesions in the aorta of apoE-/- mice. We found that HT markedly lowered the levels of serum TG, TC, and LDL-C approximately by 17.4% (p=0.004), 15.2% (p=0.003), and 17.9% (p=0.009), respectively, as well as hepatic TG and TC by 15.0% (p<0.001) and 12.3% (p=0.003), respectively, while inducing a 26.9% (p=0.033) increase in serum HDL-C. Besides, HT improved hepatic steatosis and lipid deposition. Then, we discovered that HT could regulate the signal flow of AMPK/SREBP2 and increase the expression of ABCA1, apoAI, and SRBI. In addition, HT reduced the levels of serum CRP, TNF-α, IL-1β, and IL-6 approximately by 23.5% (p<0.001), 27.8% (p<0.001), 18.4% (p<0.001), and 19.1% (p<0.001), respectively, and induced a 1.4-fold increase in IL-10 level (p=0.014). Further, we found that HT might regulate cholesterol metabolism via decreasing phosphorylation of p38, followed by activation of AMPK and inactivation of NF-κB, which in turn triggered the blockade of SREBP2/PCSK9 and upregulation of LDLR, apoAI, and ABCA1, finally leading to a reduction of LDL-C and increase of HDL-C in the circulation. Conclusion. Our results provide the first evidence that HT displays antiatherosclerotic actions via mediating lipid metabolism-related pathways through regulating the activities of inflammatory signaling molecules.

Single-unit responses of serotonergic neurons to glucose and insulin administration in behaving cats

1989 ◽  
Vol 257 (6) ◽  
pp. R1345-R1353 ◽  
Author(s):  
C. A. Fornal ◽  
W. J. Litto ◽  
D. A. Morilak ◽  
B. L. Jacobs
Keyword(s):  
Blood Glucose ◽  
Single Unit ◽  
Fold Increase ◽  
Insulin Administration ◽  
Behavioral Arousal ◽  
Serotonergic Neurons ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Arousal Response ◽  
Freely Moving Cats

Extracellular single-unit activity of serotonergic neurons in the dorsal raphe nucleus (DRN) was recorded in response to glucose loading and insulin administration in conscious, freely moving cats. Serotonergic neurons were identified based on their discharge characteristics, activity across states of behavioral arousal, response to systemic administration of serotonin autoreceptor agonists, and histological localization to the DRN. The spontaneous activity of serotonergic neurons varied in association with behavioral state, reaching their highest level during arousal and their lowest level during rapid-eye-movement sleep, when cells typically stopped firing. The activity of serotonergic DRN neurons was not significantly altered by a glucose load (500 mg/kg iv) that produced an approximately 3.5-fold increase in blood glucose levels. Furthermore, serotonergic DRN neuronal activity was not significantly altered after insulin administration (2-4 IU/kg iv), which lowered blood glucose approximately 50% below control levels, or after the rapid reversal of hypoglycemia by subsequent glucose administration. These results indicate that the activity of serotonergic DRN neurons is unrelated to alterations in blood glucose and is not sensitive to elevations of endogenous circulating insulin levels or to exogenous insulin administration. Furthermore, changes in the activity of serotonergic DRN neurons does not appear to be a component of glucoregulatory mechanisms invoked by either hyper- or hypoglycemia. Overall, these results do not support a role for serotonergic DRN neurons in glucoregulation in the cat.

scholarly journals Study on optimization and stability of a single dose streptozotocin-induced diabetic modeling in rats

2020 ◽  
Author(s):  
Yao Zhang ◽  
jiao Zhang ◽  
Ming Hong ◽  
Jingyi Huang ◽  
Rui Wang ◽  
...  
Keyword(s):  
Blood Glucose ◽  
High Fat Diet ◽  
Female Rats ◽  
Male Rats ◽  
Control Group ◽  
High Fat ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Sd Rats ◽  
Male And Female Rats

Abstract BackgroundOptimization of experimental conditions in streptozotocin induced diabetic model in Sprague Dawley (SD) rats to evaluate the stability of the model.MethodsMale and female SD rats were randomly divided into control group, STZ 45 group (STZ: 45 mg / kg), STZ 65 group (STZ: 65 mg / kg), STZ 85 group (STZ: 85 mg / kg), high fat diet with STZ 45 group (STZ: 45 mg / kg), high fat diet with STZ 65 group (STZ: 65 mg / kg), high fat diet with STZ 85 group (STZ: 85 mg / kg). N = 6 in each group. The changes of body weight and blood glucose were observed dynamically.ResultsThere was no significant difference in blood glucose or body weight between the STZ 45 group and the control group in both male and female rats, whether or not they were on a high-fat diet. However, there were significant differences in blood glucose between the high-dose STZ group and the control group in both male and female rats, regardless of whether the rats were on a high-fat diet or not (P < 0.05 or P < 0.01). Compared with the control group, there were significant differences in blood glucose levels (P < 0.05 or P < 0.01) and higher blood glucose levels in the male rats fed with the normal diet than that in those fed with the high-fat diet.ConclusionsIn this study, male rats fed with ordinary feed and injected STZ dose of 65 mg / kg were the most stable and ideal diabetic rat.

scholarly journals PA and OA Induce Abnormal Glucose Metabolism by Inhibiting KLF15 in Adipocytes

2021 ◽  
Author(s):  
Cuizhe Wang ◽  
Xiaolong Chu ◽  
Yuchun Deng ◽  
Jingzhou Wang ◽  
Tongtong Qiu ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
P38 Mapk ◽  
High Fat Diet ◽  
Elevated Serum ◽  
Glucose Levels ◽  
Abnormal Glucose Metabolism ◽  
Blood Glucose Levels ◽  
Visceral Adipose ◽  
Mapk Signal Pathway

Abstract Background: Obesity-induced elevated serum free fatty acids (FFAs) levels result in the occurrence of type 2 diabetes mellitus (T2DM). However, the molecular mechanism remains largely enigmatic. This study was to explore the effect and mechanism of KLF15 on FFAs-induced abnormal glucose metabolism. Methods: Levels of TG, TC, HDL-C, LDL-C, and glucose were measured by different assay kits. qRT-PCR and Western Blot were used to detect the levels of GPR120, GPR40, phosphorylation of p38 MAPK, KLF15, and downstream factors. Results: KLF15 was decreased in visceral adipose tissue of obesity subjects and high-fat diet (HFD) mice. In HFD mice, GPR120 antagonist significantly promoted KLF15 protein expression level and phosphorylation of p38 MAPK, meanwhile reduced the blood glucose levels. While, blocking GPR40 inhibited the KLF15 expression. In 3T3-L1 adipocytes, 1500 μM PA inhibited KLF15 through a GPR120/P-p38 MAPK signal pathway, and 750 μM OA inhibited KLF15 mainly through GPR120 while not dependent on P-p38 MAPK, ultimately resulting in abnormal glucose metabolism. Unfortunately, GPR40 didn’t contribute to PA or OA-induced KLF15 reduction. Conclusions: Both PA and OA inhibit KLF15 expression through GPR120, leading to abnormal glucose metabolism in adipocytes. Notably, the inhibition of KLF15 expression by PA depends on phosphorylation of p38 MAPK.

Abstract 347: Water-soluble Components of Sesame Oil Reduces Inflammation and Atherosclerosis

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Chandrakala Aluganti Narasimhulu ◽  
Krithika Selvarajan ◽  
Kathryn Burge ◽  
Dmitry Litvinov ◽  
Bhaswati Sengupta ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Plasma Lipids ◽  
Cholesterol Metabolism ◽  
Plasma Cholesterol ◽  
Sesame Oil ◽  
Water Soluble ◽  
Gene Analysis ◽  
High Fat ◽  
Atherosclerotic Lesions ◽  
Anti Inflammatory

Background: Atherosclerosis, a major form of cardiovascular disease, has now been recognized as a chronic inflammatory disease. Non-pharmacological means of treating chronic diseases have gained attention recently. We previously reported that the sesame oil aqueous extract (SOAE) has anti-inflammatory properties both in vitro and in vivo. In this study, we have determined whether SOAE has anti-atherosclerotic properties, and mechanisms by which it might modulate atherosclerosis by identifying genes and inflammatory markers. Methods and results: Low-density lipoprotein receptor knockout (LDLR-/-) female mice were fed with either high fat diet or high fat diet supplemented with SOAE. Plasma lipids and atherosclerotic lesions were quantified after 3 months of feeding. Plasma samples were used for global cytokine array. RNA was extracted from the liver tissue and the aorta and used for gene analysis. The SOAE-supplemented high fat diet significantly reduced atherosclerotic lesions, plasma cholesterol, and LDL cholesterol levels in LDLR-/- mice. Plasma inflammatory cytokines were reduced, but not significantly, demonstrating an anti-inflammatory property of SOAE. Gene analysis showed that SOAE-supplemented high fat diet reduced the genes involved in inflammation, and induced genes involved in cholesterol metabolism and reverse cholesterol transport. Conclusion: In conclusion, our studies suggest that a SOAE-enriched diet could be an effective non-pharmacological treatment for atherosclerosis by controlling inflammation and regulating lipid metabolism.

scholarly journals Discovery, optimization, and evaluation of non-bile acid FXR/TGR5 dual agonists

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sachiho Miyata ◽  
Yuji Kawashima ◽  
Miku Sakai ◽  
Masaya Matsubayashi ◽  
Keisuke Motoki ◽  
...  
Keyword(s):  
Bile Acid ◽  
High Fat Diet ◽  
Farnesoid X Receptor ◽  
High Concentration ◽  
Vitro Assay ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
G Protein Coupled ◽  
Dual Agonist

AbstractAlthough several potent bile acid Farnesoid X receptor (FXR) and Takeda G-protein-coupled receptor 5 (TGR5, GPBAR1) dual agonists such as INT-767 have been reported, no non-bile acid FXR/TGR5 dual agonist has been investigated to date. Therefore, we attempted to discover potent non-bile acid FXR/TGR5 dual agonists and identified some non-bile acid FXR/TGR5 dual agonists, such as isonicotinamide derivatives in vitro assay. Compound 20p was evaluated in C57BL/6J mice, that were administered a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) consisting of 60 kcal% fat and 0.1% methionine by weight for one week. Compound 20p dose-dependently induced small heterodimer partner (SHP) mRNA and decreased cytochrome P450 7A1 (CYP7A1) in the liver at 10 and 30 mg/kg, respectively, which were used as FXR agonist markers. Compound 20p significantly increased the plasma levels of GLP-1 as a TGR5 agonist, and a high concentration of GLP-1 lowered blood glucose levels. We confirmed that compound 20p was a non-bile acid FXR/TGR5 dual agonist.

Compensatory Recovery of Blood Glucose Levels in KKAy Mice Fed a High-Fat Diet: Insulin-Sparing Effects of PACAP Overexpression in β Cells

2012 ◽  
Vol 48 (3) ◽  
pp. 647-653 ◽  
Author(s):  
Yusuke Sakurai ◽  
Hiroaki Inoue ◽  
Norihito Shintani ◽  
Akihiro Arimori ◽  
Ken-ichi Hamagami ◽  
...  
Keyword(s):  
Blood Glucose ◽  
High Fat Diet ◽  
High Fat ◽  
Β Cells ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Kkay Mice
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