scholarly journals 9-PAHSA Improves Cardiovascular Complications by Promoting Autophagic Flux and Reducing Myocardial Hypertrophy in Db/Db Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Yan-Mei Wang ◽  
Shou-Ling Mi ◽  
Hong Jin ◽  
Qi-Lin Guo ◽  
Zhong-Yu Yu ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Blood Glucose ◽  
Western Blot ◽  
Vascular Calcification ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Myocardial Hypertrophy ◽  
Autophagic Flux ◽  
Glucose Levels ◽  
Blood Glucose Levels

Atherosclerotic cardiovascular disease is a common and severe complication of diabetes. There is a large need to identify the effective and safety strategies on diabetic cardiovascular disease (DCVD). 9-PAHSA is a novel endogenous fatty acid, and has been reported to reduce blood glucose levels and attenuate inflammation. We aim to evaluate the effects of 9-PAHSA on DCVD and investigate the possible mechanisms underlying it. Firstly, serum 9-PAHSA levels in human were detected by HPLC-MS/MS analysis. Then 9-PAHSA was synthesized and purified. The synthesized 9-PAHSA was gavaged to db/db mice with 50 mg/kg for 4 weeks. The carotid arterial plaque and cardiac structure was assessed by ultrasound. Cardiac autophagy was tested by western blot analysis, electron microscope and iTRAQ. The results showed that 9-PAHSA, in patients with type 2 diabetes mellitus (T2DM), was significantly lower than that in non-diabetic subjects. Administration of 9-PAHSA for 2 weeks reduced blood glucose levels. Ultrasound observed that continue administration of 9-PAHSA for 4 weeks ameliorated carotid vascular calcification, and attenuated myocardial hypertrophy and dysfunction in db/db mice. Electron microscopy showed continue 9-PAHSA treatment significantly increased autolysosomes, while dramatically decreased greases in the myocardial cells of the db/db mice. Moreover, iTRAQ analysis exhibited that continue 9-PAHSA treatment upregulated BAG3 and HSPB8. Furthermore, western blot analysis confirmed that 9-PAHSA down-regulated Akt/mTOR and activated PI3KIII/BECN1 complex in diabetic myocardium. Thus, 9-PAHSA benefits DCVD in diabetic mice by ameliorating carotid vascular calcification, promoting autophagic flux and reducing myocardial hypertrophy.

scholarly journals Study on the prevalence of dyslipidemia in type 2 diabetes mellitus

2019 ◽  
Vol 6 (3) ◽  
pp. 786
Author(s):  
Eda Dayakar ◽  
C. Sathya Sree ◽  
E. Sanjay
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Diabetic Patients ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Type 2 Diabetic

Background: Diabetes mellitus is a common health problem globally. Dyslipidaemia is a major risk factor to develop cardiovascular disease in diabetics. They present study was undertaken to find out the prevalence of dyslipidaemia in type 2 diabetic patients.Methods: The present study was a cross sectional study consisting of 46 (23 male and 23 female) known type 2 diabetes mellitus patients. Age, gender, duration of diabetes, body mass index (BMI) was recorder in all the diabetic patients.  Fasting blood glucose levels, total cholesterol, triglycerides, HDL, LDL, VLDL levels were measured using standard methods and recorded.Results: The average total cholesterol, triglycerides, LDL, HDL and VLDL were 200±42mg/dl, 169.62±89.79mg/dl, 132.45±36.38mg/dl,39.1±16.6mg/dl and 35.85±17.09mg/dl respectively. The incidence of occurrence of hypercholesterolemia was 58.6% and hypertriglyceridemia 36.9%. Increased levels of LDL were observed in 30 (65.2%) patients and reduced HDL was observed in 43 (93.4%) patients. The incidence rate of dyslipidaemia was higher in female diabetic patients when compared to male diabetic patients.Conclusions: Awareness on the dyslipidaemia and its risk factors should be provided to the type 2 diabetic patients as they are more prone to get cardiovascular disease and lipid profile also should be monitored regularly along with blood glucose levels.

scholarly journals Cardiovascular effects of glucagon-like peptide 1 receptor agonists: from mechanistic studies in humans to clinical outcomes

2019 ◽  
Vol 116 (5) ◽  
pp. 916-930 ◽  
Author(s):  
Valerie D Heuvelman ◽  
Daniël H Van Raalte ◽  
Mark M Smits
Keyword(s):  
Cardiovascular Disease ◽  
Blood Glucose ◽  
Cardiovascular Effects ◽  
Lifestyle Changes ◽  
Mechanistic Studies ◽  
Receptor Agonists ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Type 2 diabetes mellitus (T2DM) is currently one of the most prevalent diseases, with as many as 415 million patients worldwide. T2DM is characterized by elevated blood glucose levels and is often accompanied by several comorbidities, such as cardiovascular disease. Treatment of T2DM is focused on reducing glucose levels by either lifestyle changes or medical treatment. One treatment option for T2DM is based on the gut-derived hormone glucagon-like peptide 1 (GLP-1). GLP-1 reduces blood glucose levels by stimulating insulin secretion, however, it is rapidly degraded, and thereby losing its glycaemic effect. GLP-1 receptor agonists (GLP-1RAs) are immune to degradation, prolonging the glycaemic effect. Lately, GLP-1RAs have spiked the interest of researchers and clinicians due to their beneficial effects on cardiovascular disease. Preclinical and clinical data have demonstrated that GLP-1 receptors are abundantly present in the heart and that stimulation of these receptors by GLP-1 has several effects. In this review, we will discuss the effects of GLP-1RA on heart rate, blood pressure, microvascular function, lipids, and inflammation, as measured in human mechanistic studies, and suggest how these effects may translate into the improved cardiovascular outcomes as demonstrated in several trials.

scholarly journals Korelasi Lingkar Pinggang dengan Kadar Gula Darah Puasa, Kadar Trigliserida, dan Tekanan Darah pada Mahasiswa Fakultas Kedokteran Universitas HKBP Nommensen

2021 ◽  
Vol 3 (2) ◽  
pp. 08-13
Author(s):  
Ervina Julien Sitanggang
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Young Adults ◽  
Blood Glucose ◽  
Waist Circumference ◽  
Blood Sugar ◽  
Fasting Blood Glucose ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Sugar Levels

Introduction: Cardiovascular disease is the number one cause of death globally with an incidence of adolescents and young adults in Indonesia as many as 153.705 cases. Central obesity is associated with the risk of cardiovascular disease due to increase in fasting blood glucose levels, cholesterol and triglyceride levels, and blood pressure. Aims: to determine the correlation between waist circumference and fasting blood glucose levels, triglyceride levels, and blood pressure in young adults. Method: This analytic study with a cross-sectional approach involved 53 young adult subjects (18-25 years old). Waist circumference is measured using a tape measure. Blood sugar and triglyceride levels were measured using Cobas® 6000 analyzer machine from blood samples of subjects after fasting for 8-12 hours. Blood pressure data are obtained by measurement using aneroid sphygmomanometer. Results: In this study, the mean waist circumference of the research subjects was 77,4 cm. No correlation was found between waist circumference and fasting blood sugar levels (p = 0,159). However, a positive correlation was found between waist circumference and triglyceride levels (p = 0,008; r = 0,332), between waist circumference and systolic blood pressure (p = 0,049; r = 0,230), and between waist circumference and diastolic blood pressure (p = 0,017; r = 0,293). Conclusion: waist circumference is positively correlated with triglyceride levels and blood pressure, but does not correlate with fasting blood sugar levels.

scholarly journals PERBANDINGAN KADAR GULA DARAH POST-PRANDIAL PADA WANITA OBES SENTRAL DENGAN DAN TANPA RIWAYAT KELUARGA PENYAKIT KARDIOVASKULAR

2013 ◽  
Vol 5 (1) ◽  
Author(s):  
Arum P. S. Widyaningrum ◽  
Sunny Wangko ◽  
George N. Tanudjaja
Keyword(s):  
Cardiovascular Disease ◽  
Blood Glucose ◽  
Inflammatory Process ◽  
Obese Women ◽  
Cross Sectional ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Family Histories ◽  
Significant Difference ◽  
Disease Family

Abstract: Inflammatory process plays some important roles in the occurence of insulin resistance in obesity which inhibits the glucose molecules from entering the cells. In obesity, adipocytes produce active biological molecules called adipokines, some of which worsen the inflammatory process. Insulin resistance results in increases of fasting and post-prandial blood glucose. This study aimed to determine the comparison of post-prandial glucose in central obese women with and without family histories of cardiovascular diseases. This was a cross sectional design study, using a purposive sampling method. This study was carried out at Kairagi Weru Lingkungan IV, Manado.There were 44 respondents that met the inclusion criteria. The data used were BMI, waist circumference, questionnaires, and 2-hour-post-prandial blood glucose examinations. The results showed that most of the respondents were 46-50 years old. For all respondents, there was no significant correlation (P > 0.05) between ages and post-prandial blood glucose levels, or between the BMIs and post-prandial blood glucose levels. The statistic analysis showed that there was no correlation (P = 0.680) between cardiovascular disease family histories and post-prandial blood glucose levels. Besides that, there was no significant difference (P = 0.209) between post-prandial blood glucose levels among samples with or without cardiovascular disease family histories. Conclusion: There was no significant difference in the 2-hour-post-prandial blood glucose levels among the central obese women with or without family histories of cardiovascular diseases. Keywords: cardiovascular disease, central obesity, family history, postprandial.    Abstrak: Reaksi inflamasi berperan dalam resistensi insulin pada obesitas yang mengakibatkan glukosa sulit memasuki sel. Pada obesitas, adiposit menghasilkan molekul biologis aktif, yaitu adipokin; beberapa di antaranya memperburuk proses inflamasi. Resistensi insulin menghasilkan peningkatan kadar gula darah puasa dan post-prandial. Penelitian ini bertujuan untuk mengetahui perbandingan kadar gula darah dua jam post-prandial pada wanita obes sentral dengan atau tanpa riwayat keluarga penyakit kardiovaskular. Penelitian ini menggunakan desain cross sectional dan dilakukan di Kelurahan Kairagi Weru Lingkungan IV pada bulan Oktober-November 2012. Sampel sebanyak 44 orang, yang didapatkan dengan menggunakan teknik purposive sampling. Data diperoleh melalui pemeriksaan IMT dan LP, pengisian kuesioner, serta pemeriksaan kadar gula darah dua jam post-prandial. Hasil penelitian memperlihatkan bahwa sebagian besar sampel berusia 46-50 tahun. Analisis statistik menunjukkan untuk semua sampel tidak terdapat korelasi bermakna (P > 0,05) antara usia dan kadar gula darah post-prandial, atau antara IMT dan kadar gula darah post-prandial. Tidak terdapat korelasi (P = 0,680) antara sampel yang dengan atau tanpa riwayat keluarga penyakit kardiovaskular dan kadar gula darah post-prandial. Selain itu, tidak terdapat perbedaan bermakna (P = 0,209) antara kadar gula darah post-prandial blood glucose levels pada sampel dengan dan tanpa riwayat keluarga penyakit kardiovaskular. Simpulan: Tidak terdapat perbedaan bermakna antara kadar gula darah dua jam postprandial pada wanita obes sentral dengan dan tanpa riwayat keluarga penyakit kardiovaskular. Kata kunci: obes sentral, postprandial, penyakit kardiovaskular, riwayat keluarga.

Abstract 29: MiR-33 Coordinately Regulates Macrophage Autophagy

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Mireille Ouimet ◽  
Hasini Ediriweera ◽  
Bhama Ramkhelawon ◽  
Elizabeth Hennessy ◽  
Denuja Karunakaran ◽  
...  
Keyword(s):  
Western Blot ◽  
Quantitative Pcr ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Cholesterol Efflux ◽  
Energy Homeostasis ◽  
Cholesterol Metabolism ◽  
Autophagic Flux ◽  
Microrna Target

Macrophage autophagy is thought to be essential for protecting from atherosclerosis, and compromised autophagy in macrophages of the artery wall leads to a number of pathologic processes including activation of the inflammasome, defective efferocytosis, and impaired cholesterol metabolism. Autophagy of lipid droplets (LDs) or “lipophagy” catabolizes stored lipids to maintain cellular energy homeostasis and plays a key role in cholesterol efflux by regulating LD-cholesterol mobilization, a rate-limiting step in macrophage reverse cholesterol transport (RCT). MicroRNA-33 (miR-33) is a well-established post-transcriptional RCT regulator, yet the complete mechanisms by which anti-miR33 exerts its beneficial effects on cholesterol metabolism are not known. Notably, microRNA target prediction algorithms identify a number of essential autophagy-related proteins (ATG5, ATG7) and lysosomal effectors (lysosomal-associated membrane protein 1 [LAMP1], lysosomal acid lipase [LAL]) as putative miR-33 targets. Quantitative PCR array profiling in mouse peritoneal macrophages revealed that a high proportion of autophagy genes are reciprocally regulated by miR-33 overexpression and inhibition. We validated a subset of genes in the autophagy pathway as bona fide miR-33 targets using 3′UTR luciferase assays and confirmed regulation of these targets by miR-33 using quantitative PCR and western blot analysis. Furthermore, we show that miR-33 indirectly regulates the expression of two master regulators of autophagy and lysosomal biogenesis gene programs: forkhead box O (FOXO) 3 and transcription factor EB (TFEB), via targeting of 5' AMP-activated protein kinase (AMPK). Inhibition of miR-33 in peritoneal macrophage in vitro enhanced cellular autophagic flux, as observed by fluorescence microscopy and western blot analysis, and autophagy was required for anti-miR33 promotion of cholesterol efflux. Furthermore, anti-miR33 treatment of atherosclerotic Ldlr-/- mice enhanced autophagy in plaque macrophages and triggered atherosclerosis regression. These data describe a novel role for miR-33 in the regulation of autophagy and identify additional mechanisms by which anti-miR33 therapy protects against atherosclerosis.

Dihydroartemisinin Ameliorates Decreased Neuroplasticity-Associated Proteins and Excessive Neuronal Apoptosis in APP/PS1 Mice

2020 ◽  
Vol 17 ◽  
Author(s):  
Yueyang Zhao ◽  
Zhimin Long ◽  
Yuanjie Liu ◽  
Min Luo ◽  
Yu Qiu ◽  
...  
Keyword(s):  
Western Blot ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Neuronal Apoptosis ◽  
Caspase 3 ◽  
Senile Plaques ◽  
Autophagic Flux ◽  
Neuron Loss ◽  
Associated Proteins

Objective: Alzheimer’s disease (AD) is one of the worst neurodegenerative disorders worldwide, with extracellular senile plaques (SP), subsequent intracellular neurofibrillary tangles (NFTs) and final neuron loss and synaptic dysfunction as the main pathological characteristics. Excessive apoptosis is the main cause of irreversible neuron loss. Thus, therapeutic intervention for these pathological features has been considered a promising strategy to treat or prevent AD. Dihydroartemisin (DHA) is a widely used first-line drug for malaria. Our previous study showed that DHA treatment significantly accelerated Aβ clearance, improved memory and cognitive deficits in vivo and restored autophagic flux both in vivo and in vitro. Methods: The present study intended to explore the neuroprotective effect of DHA on neuron loss in APP/PS1 double-transgenic mice and the underlying mechanisms involved. Transmission electron microscope (TEM) analysis showed that DHA significantly reduced the swollen endoplasmic reticulum (ER) in APP/PS1 mice. Western blot analysis indicated that DHA upregulated the level of NeuN, NeuroD, MAP2, and synaptophysin and promoted neurite outgrowth. Meanwhile, DHA greatly corrected the abnormal levels of Brain-derived neurotrophic factor (BDNF) and rescued the neuronal loss in the hippocampal CA1 area. Western blot analysis revealed that DHA notably down-regulated the protein expression of full length caspase-3, cleaved caspase-3 and Bax. Results: In parallel, the expression of the antiapoptotic protein Bcl-2 increased after oral DHA treatment. Altogether, these results indicate that DHA protected AD mice from neuron loss via promoting the expression of BDNF and other neuroplasticity-associated proteins and suppressing the inhibition of neuronal apoptosis.

scholarly journals Sennoside A induces GLP-1 secretion through activation of the ERK1/2 pathway in L-cells

2020 ◽  
Author(s):  
Li Ma ◽  
Xinyu Cao ◽  
Xiaotong Ye ◽  
Jianping Ye ◽  
Yongning Sun
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Blood Glucose ◽  
Western Blot ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Oral Glucose ◽  
High Dose ◽  
L Cells

Abstract Background Glucagon-like peptide-1 (GLP-1) is secreted from the intestinal L-cells to stimulate insulin secretion in the control of blood glucose. Sennoside A (SA), derived from Rhubarb extract of traditional Chinese medicine, is often used to treat constipation and lose weight. Our previous study suggests that SA can increase the plasma GLP-1 level in a mouse model of type 2 diabetes. However, the mechanism of SA activity remains unknown. This issue was addressed in this study. Methods C57bl/6 mice were divided randomly into four groups at n = 12. Group one was used as a control group without drug treatment. The other three groups were treated with (SA) at three dosages: a low dose (15 mg/kg/day), medium dose (30mg/kg/day) or high dose (45 mg/kg/day). SA was delivered into the mice through drinking water. Bodyweight was monitored. After treatment, blood glucose was assayed by OGTT. Plasma GLP-1 and insulin were determined at 15 mins of oral glucose challenge. Colon tissues were collected for mRNA or western blot analysis. Immunofluorescence staining assays was used to evaluate the number of β-cells and L-cells. NCI-H716 cells were employed to investigate the mechanism of SA-induced GLP-1 secretion, and the cells were subjected to western blot analysis. In the study of extracellular signal-regulated kinases 1/2 (ERK1/2) pathway, NCI-H716 cells were pretreated with ERK1/2 inhibitors (PD98059, 50 μM) for 30 min in the presence of SA (100 μM). Results In the current study, SA can reduce body weight during 5 weeks of weight monitoring and improve OGTT in C57BL/6 mice on the Chow diet. Furthermore, plasma GLP-1 was significantly elevated in the mouse treated by SA at the dosage of 45 mg/kg/day. The SA activity was supported by improving glucose-induced insulin secretion. Meanwhile, increased expression of EKR1/2 and prohormone convertase 1/3 (PC1/3) proteins was observed in the large intestine of SA-treated mice. The number of L-cells was not altered in each group. In the NCI-H716 cells, GLP-1 secretion was induced by SA with activation of the ERK1/2 pathway and elevation of PC1/3 protein. The SA effect was blocked by the ERK1/2 inhibitor. These data suggest that SA induced GLP-1 secretion in L-cells through activation of the ERK1/2 pathway in the mouse intestine. Conclusion Our study provides direct evidence that SA interacts with L cells for GLP-1 secretion. The data suggest that the SA effect is dependent on the ERK1/2 signaling pathway. Therefore, SA is a new drug candidate for the treatment of type 2 diabetes by induction of GLP-1 secretion.

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