scholarly journals Glucagon-like peptide-1 analog prevents obesity-related glomerulopathy by inhibiting excessive autophagy in podocytes

2018 ◽  
Vol 314 (2) ◽  
pp. F181-F189 ◽  
Author(s):  
Honglei Guo ◽  
Bin Wang ◽  
Hongmei Li ◽  
Lilu Ling ◽  
Jianying Niu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Plasma Membrane ◽  
High Fat Diet ◽  
Glucose Transporter ◽  
Periodic Acid ◽  
Fasting Blood Glucose ◽  
High Fat ◽  
Periodic Acid Schiff ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

To investigate the role of glucagon-like peptide-1 analog (GLP-1) in high-fat diet-induced obesity-related glomerulopathy (ORG). Male C57BL/6 mice fed a high-fat diet for 12 wk were treated with GLP-1 (200 μg/kg) or 0.9% saline for 4 wk. Fasting blood glucose and insulin and the expression of podocin, nephrin, phosphoinositide 3-kinase (PI3K), glucose transporter type (Glut4), and microtubule-associated protein 1A/1B-light chain 3 (LC3) were assayed. Glomerular morphology and podocyte foot structure were evaluated by periodic acid-Schiff staining and electron microscopy. Podocytes were treated with 150 nM GLP-1 and incubated with 400 μM palmitic acid (PA) for 12 h. The effect on autophagy was assessed by podocyte-specific Glut4 siRNA. Insulin resistance and autophagy were assayed by immunofluorescence and Western blotting. The high-fat diet resulted in weight gain, ectopic glomerular lipid accumulation, increased insulin resistance, and fusion of podophyte foot processes. The decreased translocation of Glut4 to the plasma membrane and excess autophagy seen in mice fed a high-fat diet and in PA-treated cultured podocytes were attenuated by GLP-1. Podocyte-specific Glut4 siRNA promoted autophagy, and rapamycin-enhanced autophagy worsened the podocyte injury caused by PA. Excess autophagy in podocytes was induced by inhibition of Glut4 translocation to the plasma membrane and was involved in the pathology of ORG. GLP-1 restored insulin sensitivity and ameliorated renal injury by decreasing the level of autophagy.

MiR-425-5p Regulates Glucagon-like Peptide-1 Production and Affects Blood Glucose Levels in High-fat Diet-fed Mice

2021 ◽  
Author(s):  
Lirui Wei ◽  
Xuenan Zhao ◽  
Feng Guo ◽  
Fengjiao Huang ◽  
Yanyan Zhao ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Protein Level ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Tolerance Test ◽  
Control Group ◽  
High Fat ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract BackgroundIn modern society, obesity has become a global problem with resulting in metabolic disorders and poses high risk for type 2 diabetes mellitus (T2DM). The glucagon-like peptide-1 (GLP-1) has been taken as an effective drug for the therapy of T2DM and obesity. In the present study, the regulatory roles and molecular mechanisms of miR-425-5p in GLP-1 secretion in high-fat diet (HFD)-induced diabetic mice were explored. MethodsOral glucose tolerance test and insulin tolerance test were performed to assess glucose metabolism and GLP-1 and LPS levels. Quantitative real time polymerase chain reaction (qRT-PCR) was employed to detect the expression of LPS, GLP-1, GLP-1 receptors, miR-425-5p, phosphatase and tensin homology (PTEN), proglucagon, p65 and β-catenin. Western blot was performed to determine the expression of proglucagon, p65, β-catenin and PTEN. ResultsThe results showed that plasma GLP-1 level was negatively correlated with plasma LPS level in HFD-fed mice, and miR-425-5p expression and LPS level were up-regulated in the ileal fluid compared with control groups. LPS injection boosted miR-425-5p expression in ileum. MiR-425-5p ameliorated glucose intolerance and insulin resistance in HFD-fed mice by increasing GLP-1 secretion. Furthermore, p65 protein level in the cytoplasmic and nuclear in the ileum of HFD-fed mice was increased compared with the control group. MiR-425-5p agomir elevated nuclear β-catenin protein level, but reduced PTEN protein level in HFD-fed mice compared with HFD-fed mice treated with the miR-425-5p antagomir. ConclusionsOur results suggest that miR-425-5p promotes GLP-1 secretion and improves glucose tolerance and insulin resistance in high-fat diet-fed mice.

scholarly journals Brain Glucagon-Like Peptide 1 Signaling Controls the Onset of High-Fat Diet-Induced Insulin Resistance and Reduces Energy Expenditure

Endocrinology ◽  
2008 ◽  
Vol 149 (10) ◽  
pp. 4768-4777 ◽  
Author(s):  
Claude Knauf ◽  
Patrice D. Cani ◽  
Afifa Ait-Belgnaoui ◽  
Alexandre Benani ◽  
Cédric Dray ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Energy Expenditure ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Carbon Dioxide Production ◽  
High Fat ◽  
Ambulatory Activity ◽  
Ucp2 Expression ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1) is a peptide released by the intestine and the brain. We previously demonstrated that brain GLP-1 increases glucose-dependent hyperinsulinemia and insulin resistance. These two features are major characteristics of the onset of type 2 diabetes. Therefore, we investigated whether blocking brain GLP-1 signaling would prevent high-fat diet (HFD)-induced diabetes in the mouse. Our data show that a 1-month chronic blockage of brain GLP-1 signaling by exendin-9 (Ex9), totally prevented hyperinsulinemia and insulin resistance in HFD mice. Furthermore, food intake was dramatically increased, but body weight gain was unchanged, showing that brain GLP-1 controlled energy expenditure. Thermogenesis, glucose utilization, oxygen consumption, carbon dioxide production, muscle glycolytic respiratory index, UCP2 expression in muscle, and basal ambulatory activity were all increased by the exendin-9 treatment. Thus, we have demonstrated that in response to a HFD, brain GLP-1 signaling induces hyperinsulinemia and insulin resistance and decreases energy expenditure by reducing metabolic thermogenesis and ambulatory activity.

scholarly journals Effect of Baicalein on GLUT4 Translocation in Adipocytes of Diet-Induced Obese Mice

2018 ◽  
Vol 50 (2) ◽  
pp. 426-436 ◽  
Author(s):  
Wen Min ◽  
Mingjie Wu ◽  
Penghua Fang ◽  
Mei Yu ◽  
Mingyi Shi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Plasma Membranes ◽  
Glucose Transporter ◽  
Fasting Blood Glucose ◽  
Enzyme Linked Immunosorbent Assay ◽  
Obese Mice ◽  
Glut4 Translocation ◽  
Intracellular Membrane ◽  
High Fat

Background/Aims: Although baicalein has been shown to increase insulin sensitivity in liver of mice, there is no literature available about the effect of baicalein on glucose transporter 4 (GLUT4) translocation from intracellular membrane pools to plasma membranes in adipocytes of diet-induced obese mice. Methods: In the present study, the obese model was induced in mice fed a high fat diet (20% carbohydrates, 21% protein and 59% fat) for 16 weeks. The diet-induced obese mice were given 20mg/kg baicalein intraperitoneally (i.p.) once a day for 21 days. The plasma insulin was measured by enzyme-linked immunosorbent assay. Fasting blood glucose and insulin resistance indexes were measured by glucose tolerance test (GTT). The expression levels of PGC-1α, UCP1, GLUT4, PPARγ, pP38MAPK, pERK and pAKT in adipocytes were determined by quantitative real-time polymerase chain reaction and western blotting. Results: The present findings showed that administration of baicalein decreased pP38MAPK, pERK and PPARγ levels, but enhanced pAKT, PGC-1α and UCP1 contents as well as GLUT4 expression in adipocytes, and reversed high fat diet-induced glucose intolerance, hyperglycemia and insulin resistance in diet-induced obese mice. Moreover, baicalein treatment increased GLUT4 concentration in plasma membranes of adipocytes, i.e. baicalein may prevent insulin resistance through the GLUT4 translocation from intracellular membrane compartments to plasma membranes in adipocytes. Conclusion: These results suggest that baicalein is a powerful and promising agent for treatment of obesity and insulin resistance via Akt/GLUT4 pathway.

High-fat diet reduces glucose transporter responses to both insulin and exercise

1994 ◽  
Vol 266 (1) ◽  
pp. R95-R101 ◽  
Author(s):  
M. N. Rosholt ◽  
P. A. King ◽  
E. S. Horton
Keyword(s):  
Insulin Resistance ◽  
Plasma Membrane ◽  
Glucose Transport ◽  
High Fat Diet ◽  
Glucose Transporter ◽  
Membrane Vesicles ◽  
Intrinsic Activity ◽  
Sprague Dawley ◽  
High Fat ◽  
Plasma Membrane Vesicles

High-fat diet (HFD) induces skeletal muscle insulin resistance. To investigate associated changes in the plasma membrane glucose transporter, male Sprague-Dawley rats were fed either chow [high-carbohydrate diet (HCD)] or HFD for 3 wk. Plasma membrane vesicles were prepared from hindlimb muscle of control, insulin-stimulated (Ins), and acutely exercised (Ex) rats. Maximal vesicle glucose transport activity (Vmax) increased threefold with Ins and Ex treatment compared with controls in HCD rats; in HFD rats, increases were less than twofold. Transporter numbers (measured by cytochalasin B binding, CB) approximately doubled with Ins and Ex in both diet groups. Intrinsic activity (carrier turnover, Vmax/CB) increased significantly with stimulation in HCD but not HFD rats. Therefore, vesicles from HFD rats showed resistance to both exercise and insulin stimulation of muscle glucose transport. Transporter number increased normally, but intrinsic activity in HFD rats did not respond. Two conclusions are discussed: 1) translocation and activation are distinct, separable steps in transporter stimulation and 2) HFD produces effects that resemble the insulin resistance of starvation.

Electroacupuncture Mitigates Endothelial Dysfunction via Effects on the Pi3K/Akt Signalling Pathway in High Fat Diet-Induced Insulin-Resistant Rats

2018 ◽  
Vol 36 (3) ◽  
pp. 162-169 ◽  
Author(s):  
Danchun Lan ◽  
Nenggui Xu ◽  
Jian Sun ◽  
Zhixing Li ◽  
Rongzhen Liao ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Endothelial Dysfunction ◽  
Pancreatic Islet ◽  
High Fat Diet ◽  
Negative Impact ◽  
Fasting Blood Glucose ◽  
Signalling Pathway ◽  
Control Group ◽  
Model Assessment ◽  
High Fat

Objective To investigate the effect of electroacupuncture (EA) on endothelial dysfunction related to high fat diet (HFD)-induced insulin resistance through the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signalling pathway. Methods Twenty-four male Sprague-Dawley rats were fed a regular diet (Control group, n=8) or a HFD (n=16) for 12 weeks to induce an insulin resistance model. HFD-fed rats were divided into two groups that remained untreated (HFD group, n=8) or received electroacupuncture (HFD+EA group, n=8). EA was applied at PC6, ST36, SP6 and BL23. At the end of the experiment, fasting blood glucose (FBG), serum insulin (FINS), serum C-peptide (C-P) and homeostatic model assessment of insulin resistance (HOMA-IR) indices were determined. Pancreatic islet samples were subjected to histopathological examination. The thoracic aorta was immunostained with anti-rat insulin receptor substrate (IRS)-1, Akt and endothelial nitric oxide synthase (eNOS) antibodies. mRNA and protein expression of IRS-1, PI3K, Akt2 and eNOS in the vascular endothelium were determined by real-time PCR and Western blot analysis, respectively. Results The bodyweight increase of the HFD+EA group was smaller than that of the untreated HFD group. Compared with the HFD group, the levels of FBG, FINS, C-P and HOMA-IR in the HFD+EA group decreased significantly (P<0.01). Histopathological evaluation indicated that EA improved pancreatic islet inflammation. The expression of endothelial markers, such as IRS-1, PI3K, Akt2 and eNOS, decreased in the HFD group, while EA treatment appeared to ameliorate the negative impact of diet. Conclusion EA may improve insulin resistance and attenuate endothelial dysfunction, and therefore could play a potential role in the prevention or treatment of diabetic complications and cardiovascular disease through the PI3K/Akt signalling pathway.

scholarly journals Oleacein Prevents High Fat Diet-Induced A Diposity and Ameliorates Some Biochemical Parameters of Insulin Sensitivity in Mice

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1829 ◽  
Author(s):  
Lepore ◽  
Maggisano ◽  
Bulotta ◽  
Mignogna ◽  
Arcidiacono ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
High Fat Diet ◽  
Fatty Acid Synthase ◽  
Glucose Transporter ◽  
Regulatory Element ◽  
Regulatory Elements ◽  
High Fat

Oleacein is one of the most abundant polyphenolic compounds of olive oil, which has been shown to play a protective role against several metabolic abnormalities, including dyslipidemia, insulin resistance, and glucose intolerance. Herein, we investigated the effects of oleacein on certain markers of adipogenesis and insulin-resistance in vitro, in 3T3-L1 adipocytes, and in vivo in high-fat diet (HFD)-fed mice. During the differentiation process of 3T3-L1 preadipocytes into adipocytes, oleacein strongly inhibited lipid accumulation, and decreased protein levels of peroxisome proliferator-activated receptor gamma (PPARγ) and fatty acid synthase (FAS), while increasing Adiponectin levels. In vivo, treatment with oleacein of C57BL/6JOlaHsd mice fed with HFD for 5 and 13 weeks prevented the increase in adipocyte size and reduced the inflammatory infiltration of macrophages and lymphocytes in adipose tissue. These effects were accompanied by changes in the expression of adipose tissue-specific regulatory elements such as PPARγ, FAS, sterol regulatory element-binding transcription factor-1 (SREBP-1), and Adiponectin, while the expression of insulin-sensitive muscle/fat glucose transporter Glut-4 was restored in HFD-fed mice treated with oleacein. Collectively, our findings indicate that protection against HFD-induced adiposity by oleacein in mice is mediated by the modulation of regulators of adipogenesis. Protection against HFD-induced obesity is effective in improving peripheral insulin sensitivity.

Effects of glucagon-like peptide-1 analog liraglutide on the systemic inflammation in high-fat-diet-induced mice

Endocrine ◽  
2019 ◽  
Vol 66 (3) ◽  
pp. 494-502 ◽  
Author(s):  
Sha Sha ◽  
Xiaoming Liu ◽  
Ruxing Zhao ◽  
Li Qing ◽  
Qin He ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
High Fat Diet ◽  
High Fat ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1
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