scholarly journals Empagliflozin, a sodium glucose co-transporter-2 inhibitor, alleviates atrial remodeling and improves mitochondrial function in high-fat diet/streptozotocin-induced diabetic rats

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Qingmiao Shao ◽  
Lei Meng ◽  
Sharen Lee ◽  
Gary Tse ◽  
Mengqi Gong ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Atrial Fibrillation ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Function ◽  
High Fat Diet ◽  
Low Dose ◽  
Control Group ◽  
High Dose ◽  
Atrial Remodeling ◽  
High Fat

Abstract Background Diabetes mellitus is an important risk factor for atrial fibrillation (AF) development. Sodium–glucose co-transporter-2 (SGLT-2) inhibitors are used for the treatment of type 2 diabetes mellitus (T2DM). Their cardioprotective effects have been reported but whether they prevent AF in T2DM patients are less well-explored. We tested the hypothesis that the SGLT-2 inhibitor, empagliflozin, can prevent atrial remodeling in a diabetic rat model. Methods High-fat diet and low-dose streptozotocin (STZ) treatment were used to induce T2DM. A total of 96 rats were randomized into the following four groups: (i) control (ii) T2DM, (iii) low-dose empagliflozin (10 mg/kg/day)/T2DM; and (iv) high-dose empagliflozin (30 mg/kg/day)/T2DM by the intragastric route for 8 weeks. Results Compared with the control group, left atrial diameter, interstitial fibrosis and the incidence of AF inducibility were significantly increased in the DM group. Moreover, atrial mitochondrial respiratory function, mitochondrial membrane potential, and mitochondrial biogenesis were impaired. Empagliflozin treatment significantly prevented the development of these abnormalities in DM rats, likely via the peroxisome proliferator-activated receptor-c coactivator 1α (PGC-1α)/nuclear respiratory factor-1 (NRF-1)/mitochondrial transcription factor A (Tfam) signaling pathway. Conclusions Empagliflozin can ameliorate atrial structural and electrical remodeling as well as improve mitochondrial function and mitochondrial biogenesis in T2DM, hence may be potentially used in the prevention of T2DM-related atrial fibrillation.

scholarly journals Berberine elevates cardiolipin in heart of offspring from mouse dams with high fat diet-induced gestational diabetes mellitus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Laura K. Cole ◽  
Genevieve C. Sparagna ◽  
Marilyne Vandel ◽  
Bo Xiang ◽  
Vernon W. Dolinsky ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Mitochondrial Function ◽  
High Fat Diet ◽  
Fatty Acid Uptake ◽  
Isoquinoline Alkaloid ◽  
Acid Uptake ◽  
High Fat ◽  
Low Fat

AbstractBerberine (BBR) is an isoquinoline alkaloid from plants known to improve cardiac mitochondrial function in gestational diabetes mellitus (GDM) offspring but the mechanism is poorly understood. We examined the role of the mitochondrial phospholipid cardiolipin (CL) in mediating this cardiac improvement. C57BL/6 female mice were fed either a Lean-inducing low-fat diet or a GDM-inducing high-fat diet for 6 weeks prior to breeding. Lean and GDM-exposed male offspring were randomly assigned a low-fat, high-fat, or high-fat diet containing BBR at weaning for 12 weeks. The content of CL was elevated in the heart of GDM offspring fed a high fat diet containing BBR. The increase in total cardiac CL was due to significant increases in the most abundant and functionally important CL species, tetralinoleoyl-CL and this correlated with an increase in the expression of the CL remodeling enzyme tafazzin. Additionally, BBR treatment increased expression of cardiac enzymes involved in fatty acid uptake and oxidation and electron transport chain subunits in high fat diet fed GDM offspring. Thus, dietary BBR protection from cardiac dysfunction in GDM exposed offspring involves improvement in mitochondrial function mediated through increased synthesis of CL.

scholarly journals Establishment of long-term high-fat diet and low dose streptozotocin-induced experimental type-2 diabetes mellitus model of insulin resistance and evaluation of seed extracts of Syzygium cumini

2021 ◽  
Vol 10 (3) ◽  
pp. 331-338
Author(s):  
Pratibha Nadig ◽  
Meharban Asanaliyar ◽  
Kevin Manohar Salis
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
High Fat Diet ◽  
Low Dose ◽  
Syzygium Cumini ◽  
High Fat ◽  
Glut 4 ◽  
Seed Extracts

Introduction: The principal mechanism responsible for reducing blood glucose is through insulin-stimulated glucose transport into skeletal muscle. The transporter protein that mediates this uptake is GLUT-4. A defect in this step is associated with reduced glucose utilization in muscle and adipose tissue, as observed in insulin-resistant type-2 diabetes mellitus (T2DM) patients. This study aimed to develop an experimental T2DM model and evaluate altered glucose transporter type 4 (GLUT-4) levels as a biomarker of insulin resistance. Antidiabetic activities of Syzygium cumini hydro-ethanolic seed extracts (SCE) were also evaluated. Methods: Adult male Wistar albino rats were fed a high-fat diet for 12 weeks and dosed intraperitoneally with streptozotocin (35 mg/kg). After treatment for 21 days, all investigations were done. The homeostasis model of assessment (HOMA) was used for the calculation of insulin resistance (HOMA-IR) and beta-cell function (HOMA-B) index. Diaphragm muscle and retroperitoneal fat were collected for real-time polymerase chain reaction (RT-PCR) studies. Results: A significant increase in fasting blood glucose, HOMA-IR, and serum lipids, and a decrease in serum insulin and HOMA-B were observed in the diabetic group, effects that reversed following pioglitazone and SCE treatment. The diabetic group showed a downregulation of GLUT-4 expression in skeletal muscle while an increase was observed in adipose tissue. Conclusion: A high-fat diet and low dose streptozotocin-induced experimental T2DM model of insulin resistance was developed to screen novel insulin sensitizers. Data generated demonstrated that altered GLUT-4 levels could be used as a biomarker of insulin resistance. Antidiabetic activity of S. cumini hydro-ethanolic seed extract was also confirmed in this study.

scholarly journals Establishment of Type 2 Diabetes Mellitus Models Using High-Fat Diet and STZ in Bama Minipigs

2021 ◽  
Author(s):  
Yuqiong Zhao ◽  
Miaomiao Niu ◽  
Jia Yunxiao ◽  
Yuan Jifang ◽  
Xiang Lei ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Low Dose ◽  
Normal Diet ◽  
Large Animal Model ◽  
Control Group ◽  
Large Animal ◽  
High Cholesterol ◽  
High Fat ◽  
Accelerated Atherosclerosis ◽  
Atherosclerotic Lesions

Abstract BackgroundIn the past 20 years, the number of adults with diabetes has tripled. For most of the researches are often conducted in rodent T2DM models, and effective drugs developed have low clinical conversion efficiency. Therefore, it is urgent to establish a large animal model to explore the pathogenesis of T2DM and formulate disease prevention and control strategies. MethodsThis study was designed to establish and validate a T2DM model in minipigs with notable hyperglycemia using a high-fat diet and low-dose streptozotocin (STZ)，and examined the influence of STZ infusion time, the difference between a high-fat diet and a high-cholesterol and high-fat diet, and the atherosclerotic lesions accelerated by diabetes. Male Bama minipigs (n=24) were randomly divided into 5 groups; the control group was fed with normal diet for 9 months; STZ+HFD group and STZ+HCFD group were infused with 90 mg/kg STZ and then fed with a high-fat diet or high-cholesterol and high-fat diet for 9 months, respectively; HFD + STZ group and HCFD + STZ group were fed with a high-fat diet or high-cholesterol and high-fat diet, respectively, for nine months (after 3 months, pigs were injected with 90 mg/kg STZ intravenously). ResultsThe results showed the serum glucose concentrations were within the normal range in all groups except for HFD + STZ group and HCFD + STZ group. Animals fed with a high-fat diet for 9 months, did not develop apparent atherosclerotic lesions; nevertheless, atherosclerotic lesions were seen in animals fed with high-cholesterol and high-fat diets. Moreover, hyperglycemia accelerated atherosclerosis (lesions on the intimal surface of the abdominal aorta, 0.44±0.29 vs. 0.28±0.26) in minipigs. ConclusionsHigh-fat/high-cholesterol and high-fat diet combined with low-dose streptozotocin successfully established T2DM in minipigs. High-fat diet could not induce apparent atherosclerosis lesions but high-cholesterol and high-fat diet could during the nine months period. Hyperglycemia accelerated atherosclerosis in the minipigs.

scholarly journals The protective effects of Crocin on testopathy in fat-fed and streptozotocin-treated diabetic rats: An experimental study

2019 ◽  
Vol 17 (2) ◽  
pp. 89 ◽  
Author(s):  
Saeed Mirzaee ◽  
Mohammad Ehsan Bayatpoor ◽  
Shima Shahyad ◽  
Mohammad Taghi Mohammadi ◽  
Zahra Bahari
Keyword(s):  
Diabetes Mellitus ◽  
Experimental Study ◽  
High Fat Diet ◽  
Sperm Count ◽  
Diabetic Group ◽  
Control Group ◽  
Male Hypogonadism ◽  
Protective Effects ◽  
Type Ii ◽  
High Fat

Background: Male hypogonadism is associated with type II diabetes mellitus due totesticular dysfunction. Medicinal plants have received considerable attention for themanagement of diabetes and its complications.Objective: The aim of present study was to evaluate the anti-diabetic and protectiveinfluence of Crocin on testopathy in diabetic rats.Materials and Methods: In this experimental study, type II of diabetes mellitus wasinduced by high-fat diet and low dose of streptozotocin. Male Wistar rats (8 weeks,150–200 gr, 18 rats; n= 6 per group) were divided into a control group (standarddiet), diabetic group (streptozotocin+high-fat diet), and treatment group (High-fatdiet+streptozotocin+Crocin at 20 mg/kg/day, i.p. for 60 days). After 60 days, animalswere euthanized, testis and epididymis were dissected, and weights of testes andsperm count were analyzed. Hematoxylin-eosin-stained was done for histopathologicalexamination. Blood samples were collected for the assessment of serum glucose andcholesterol.Results: High-fat diet and streptozotocin significantly increased the serum glucoseand cholesterol levels as compared to the control group (p≤ 0. 001). Moreover, therewas a significant decrease in the weight of right (p= 0.008) and left testes (p≤ 0. 001)and also the total sperm count (p= 0.023) in the diabetic group compared with thecontrol

The effectiveness comparisons of eugenosedin-A, glibenclamide and pioglitazone on diabetes mellitus induced by STZ/NA and high-fat diet in SHR

2021 ◽  
Author(s):  
Hui-Li Lin ◽  
Pei-Wen Cheng ◽  
Yi-Chen Tu ◽  
Bor-Chun Yeh ◽  
Bin-Nan Wu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
High Fat Diet ◽  
Lipid Synthesis ◽  
Normal Diet ◽  
Lipid Homeostasis ◽  
Control Group ◽  
Protective Effects ◽  
High Fat ◽  
Effective Agent ◽  
Treatment Groups

Abstract Objectives Eugenosedin-A (Eu-A), an adrenergic and serotonergic antagonist, is known to have anti-metabolic syndrome effects. In this study, we evaluated its protective effects against diabetes mellitus (DM) in spontaneous hypertensive rats (SHR) and compared it with two anti-diabetes medications, glibenclamide (Gli) and pioglitazone (Pio). Methods We divided 10-week-old SHRs into five groups: a control group fed a normal diet; an untreated DM group induced by injecting the SHRs with STZ/NA and feeding them a high-fat diet (HFD); and three treated groups (after giving STZ/NA and HFD) gavage given with Eu-A, Gli or Pio (5 mg/kg per day) for 4 weeks. Key findings The untreated DM group weighed less and had hyperglycaemia, hypoinsulinemia and hyperlipidemia. They were also found to have aberrant glucose-dependent insulin pathways, glucose metabolism and lipid synthesis proteins, while the controls did not. Eu-A, Gli and Pio ameliorated the above biochemical parameters in the treatment groups. Eu-A and Pio, but not Gli, improved hypertension and tachycardia. Conclusions Taken together, Eu-A ameliorated DM, hypertension and tachycardia by improving glucose, lipid homeostasis and anti-adrenergic, serotonergic activities. We concluded that Eu-A could be used in the development of an effective agent for controlling DM and its complications.

scholarly journals Farrerol ameliorates diabetic hepatopathy in rat model of type 2 diabetes mellitus via modulation of oxidativeinflammatory stress

2020 ◽  
Vol 19 (1) ◽  
pp. 71-76
Author(s):  
Li Dong ◽  
Lixia Yang ◽  
Fengsui Liu ◽  
Haitao Zhan ◽  
Xinwei Chen
Keyword(s):  
Diabetes Mellitus ◽  
Normal Control ◽  
High Fat Diet ◽  
Diabetic Control ◽  
Control Group ◽  
High Fat ◽  
Sod Activity ◽  
Treatment Groups ◽  
Tnf Α

Purpose: To investigate the effect of farrerol on diabetic hepatopathy in a rat model of type 2 diabetes mellitus (T2DM).Methods: Adult male Wistar rats (n = 40) were randomly assigned to four groups of ten rats each: normal control, diabetic control, farrerol control and treatment groups. With the exception of normal control and farrerol control groups, the rats were fed high-fat diet (HFD) for four weeks, and thereafter injected streptozotocin (STZ) at a dose of 30 mg/kg body weight intraperitoneally (i.p.) for induction of T2DM. Rats in farrerol control and treatment groups received 50 mg/kg farrerol orally/day. Serum levels of triacylglycerol (TG), total cholesterol (TC), high-density lipoprotein  cholesterol (HDL-C) and lowdensity lipoprotein cholesterol (LDL-C) were determined. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were assessed in liver homogenate while mRNA and protein expressions of glucose transporter 2 (GLUT2) were assayed in liver using real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting, respectively. Expression levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were also determined using qRT-PCR.Results: Diabetes mellitus (DM) led to significant reductions in rat body weight and SOD activity, while increasing fasting blood glucose (FBG) and MDA levels (p < 0.05). However, treatment with farrerol significantly reversed the effect of DM on these parameters (p < 0.05). The mRNA expressions of TNF-α and IL-1β were significantly higher in diabetic control group than in normal control group, but were significantly reduced after farrerol treatment (p < 0.05). Treatment with farrerol also significantly reversed the effect of DM on rat lipid profile (p < 0.05). The expression of GLUT2 protein was significantly downregulated in the liver of diabetic control rats, when compared with normal control rats, but was significantly upregulated after treatment with farrerol (p < 0.05).Conclusion: The results of this study show that farrerol alleviates STZ-induced hyperglycemia and dyslipidemia via reduction in oxidative stress and inflammation, and upregulation of GLUT2 protein expression. Thus, farrerol has antidiabetic and hepatoprotective potentials for clinical use in  humans. Keywords: Diabetes mellitus, Dyslipidemia, Farrerol, Hepatopathy, High-fat diet

scholarly journals TheMagnoliaBioactive Constituent 4-O-Methylhonokiol Protects against High-Fat Diet-Induced Obesity and Systemic Insulin Resistance in Mice

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Zhiguo Zhang ◽  
Jing Chen ◽  
Xin Jiang ◽  
Jian Wang ◽  
Xiaoqing Yan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Triglyceride Level ◽  
High Fat Diet ◽  
Low Dose ◽  
Body Weight Gain ◽  
Normal Diet ◽  
High Dose ◽  
High Fat ◽  
Bioactive Constituent

Obesity is caused by a combination of both genetic and environmental risks. Disruption in energy balance is one of these risk factors. In the present study, the preventive effect on high-fat diet- (HFD-) induced obesity and insulin resistance in mice byMagnoliabioactive constituent 4-O-methylhonokiol (MH) was compared withMagnolia officinalisextract BL153. C57BL/6J mice were fed by normal diet or by HFD with gavage-administered vehicle, BL153, low-dose MH, and high-dose MH simultaneously for 24 weeks, respectively. Either MH or BL153 slightly inhibited body-weight gain of mice by HFD feeding although the food intake had no obvious difference. Body fat mass and the epididymal white adipose tissue weight were also mildly decreased by MH or BL153. Moreover, MH significantly lowered HFD-induced plasma triglyceride, cholesterol levels and activity of alanine transaminase (ALT), liver weight and hepatic triglyceride level, and ameliorated hepatic steatosis. BL153 only significantly reduced ALT and liver triglyceride level. Concurrently, low-dose MH improved HFD-induced hyperinsulinemia and insulin resistance. Furthermore, the infiltration of mast cells in adipose tissue was decreased in MH or in BL153 treatment. These results suggested thatMagnoliabioactive constituent MH might exhibit potential benefits for HFD-induced obesity by improvement of lipid metabolism and insulin resistance.

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