scholarly journals Pengaruh Latihan Fisik terhadap Perbaikan Resistensi Insulin

2021 ◽  
Vol 2 (2) ◽  
pp. 110-114
Author(s):  
Devitya Angielevi Sukarno
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Protein Kinase ◽  
Cell Membrane ◽  
Blood Glucose Level ◽  
Insulin Signaling ◽  
Glucose Transporter ◽  
Insulin Receptor Substrate ◽  
Glucose Transporter 4 ◽  
Glut 4

Abstract--Insulin resistance underlies the pathogenesis of chronic disease, such as diabetes mellitus which has high morbidity and mortality rate. Insulin resistance is a pathological condition when cells fail to respond normally to the insulin hormone, because of insulin signaling pathway disruption. Bound between insulin and insulin’s receptor cannot phosphorylate tyrosine and fail to activate insulin receptor substrate-1 (IRS-1). This failure decrease Glucose transporter-4 (GLUT-4) expression on the skeletal muscle’s cell membrane, that leads to decrease glucose influx and increase blood glucose level. A routine physical training which does according to adequate training dose, will activate adenosin 5’monophosphate-activated protein kinase (AMPK) and lead to the translocation of GLUT-4 vesicles without insulin and insulin’s receptor bonding.GLUT-4 expression on the skeletal muscle’s cell membrane which is stimulated by muscle contraction will increase glucose influx and decrease blood glucose level. Keywords: insulin resistance; physical training; insulin signaling pathway   Abstrak--Resistensi insulin merupakan penyebab yang mendasari terjadinya penyakit kronis seperti diabetes melitus yang memiliki angka morbiditas dan mortalitas tinggi.Resistensi insulin merupakan keadaan patologis dimana terjadi kegagalan respon seluler terhadap hormon insulin akibat gangguan pada jalur sinyal insulin.Ikatan insulin pada reseptornya tidak dapat menyebabkan fosforilasi tirosin sehingga tidak dapat mengaktivasi insulin receptor substrate-1 (IRS-1). Kegagalan aktivasi tersebut akan menyebabkan penurunan ekspresi Glucose transporter-4 (GLUT-4) pada membran sel otot rangka sehingga ambilan glukosa oleh sel menurun dan glukosa darah meningkat. Latihan fisik yang dilakukan secara rutin, teratur dan sesuai dengan dosis latihan yang tepat dapat mengaktivasi adenosin 5’monophosphate-activated protein kinase (AMPK), sehingga menyebabkan translokasi vesikel berisi GLUT-4, tanpa melalui ikatan insulin dengan reseptornya. Ekspresi GLUT-4 pada membran sel yang dirangsang oleh kontraksi otot akan meningkatkan ambilan glukosa dan menurunkan glukosa darah. Kata kunci: resistensi insulin; latihan fisik; jalur sinyal insulin

scholarly journals Interleukin-1β-Induced Insulin Resistance in Adipocytes through Down-Regulation of Insulin Receptor Substrate-1 Expression

Endocrinology ◽  
2007 ◽  
Vol 148 (1) ◽  
pp. 241-251 ◽  
Author(s):  
Jennifer Jager ◽  
Thierry Grémeaux ◽  
Mireille Cormont ◽  
Yannick Le Marchand-Brustel ◽  
Jean-François Tanti
Keyword(s):  
Insulin Resistance ◽  
Protein Kinase ◽  
Insulin Receptor ◽  
Glucose Uptake ◽  
Insulin Signaling ◽  
Protein Kinase B ◽  
Transcriptional Level ◽  
Insulin Receptor Substrate ◽  
Down Regulation ◽  
Glut 4

Inflammation is associated with obesity and insulin resistance. Proinflammatory cytokines produced by adipose tissue in obesity could alter insulin signaling and action. Recent studies have shown a relationship between IL-1β level and metabolic syndrome or type 2 diabetes. However, the ability of IL-1β to alter insulin signaling and action remains to be explored. We demonstrated that IL-1β slightly increased Glut 1 translocation and basal glucose uptake in 3T3-L1 adipocytes. Importantly, we found that prolonged IL-1β treatment reduced the insulin-induced glucose uptake, whereas an acute treatment had no effect. Chronic treatment with IL-1β slightly decreased the expression of Glut 4 and markedly inhibited its translocation to the plasma membrane in response to insulin. This inhibitory effect was due to a decrease in the amount of insulin receptor substrate (IRS)-1 but not IRS-2 expression in both 3T3-L1 and human adipocytes. The decrease in IRS-1 amount resulted in a reduction in its tyrosine phosphorylation and the alteration of insulin-induced protein kinase B activation and AS160 phosphorylation. Pharmacological inhibition of ERK totally inhibited IL-1β-induced down-regulation of IRS-1 mRNA. Moreover, IRS-1 protein expression and insulin-induced protein kinase B activation, AS160 phosphorylation, and Glut 4 translocation were partially recovered after treatment with the ERK inhibitor. These results demonstrate that IL-1β reduces IRS-1 expression at a transcriptional level through a mechanism that is ERK dependent and at a posttranscriptional level independently of ERK activation. By targeting IRS-1, IL-1β is capable of impairing insulin signaling and action, and could thus participate in concert with other cytokines, in the development of insulin resistance in adipocytes.

Oxidative stress impairs insulin signal in skeletal muscle and causes insulin resistance in postinfarct heart failure

2011 ◽  
Vol 300 (5) ◽  
pp. H1637-H1644 ◽  
Author(s):  
Yukihiro Ohta ◽  
Shintaro Kinugawa ◽  
Shouji Matsushima ◽  
Taisuke Ono ◽  
Mochamad A. Sobirin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Signaling ◽  
Glucose Transporter ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Serine Phosphorylation ◽  
Glucose Transporter 4

Insulin resistance has been shown to occur as a consequence of heart failure. However, its exact mechanisms in this setting remain unknown. We have previously reported that oxidative stress is enhanced in the skeletal muscle from mice with heart failure after myocardial infarction (MI) ( 30 ). This study is aimed to investigate whether insulin resistance in postinfarct heart failure is due to the impairment of insulin signaling in the skeletal muscle caused by oxidative stress. Mice were divided into four groups: sham operated (sham); sham treated with apocynin, an inhibitor of NAD(P)H oxidase activation (10 mmol/l in drinking water); MI; and MI treated with apocynin. After 4 wk, intraperitoneal insulin tolerance tests were performed, and skeletal muscle samples were obtained for insulin signaling measurements. MI mice showed left ventricular dilation and dysfunction by echocardiography and increased left ventricular end-diastolic pressure and lung weight. The decrease in glucose level after insulin load significantly attenuated in MI compared with sham. Insulin-stimulated serine phosphorylation of Akt and glucose transporter-4 translocation were decreased in MI mice by 61 and 23%, respectively. Apocynin ameliorated the increase in oxidative stress and NAD(P)H oxidase activities measured by the lucigenin assay in the skeletal muscle after MI. It also improved insulin resistance and inhibited the decrease of Akt phosphorylation and glucose transporter-4 translocation. Insulin resistance was induced by the direct impairment of insulin signaling in the skeletal muscle from postinfarct heart failure, which was associated with the enhanced oxidative stress via NAD(P)H oxidase.

scholarly journals Adipocytes Exhibit Abnormal Subcellular Distribution and Translocation of Vesicles Containing Glucose Transporter 4 and Insulin-Regulated Aminopeptidase in Type 2 Diabetes Mellitus: Implications Regarding Defects in Vesicle Trafficking

2001 ◽  
Vol 86 (11) ◽  
pp. 5450-5456 ◽  
Author(s):  
Lidia Maianu ◽  
Susanna R. Keller ◽  
W. Timothy Garvey
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Body Mass ◽  
Glucose Transporter ◽  
Diabetic Patients ◽  
Low Density ◽  
Glucose Transporter 4 ◽  
Glut 4

Insulin resistance in type 2 diabetes is due to impaired stimulation of the glucose transport system in muscle and fat. Different defects are operative in these two target tissues because glucose transporter 4 (GLUT 4) expression is normal in muscle but markedly reduced in fat. In muscle, GLUT 4 is redistributed to a dense membrane compartment, and insulin-mediated translocation to plasma membrane (PM) is impaired. Whether similar trafficking defects are operative in human fat is unknown. Therefore, we studied subcellular localization of GLUT4 and insulin-regulated aminopeptidase (IRAP; also referred to as vp165 or gp160), which is a constituent of GLUT4 vesicles and also translocates to PM in response to insulin. Subcutaneous fat was obtained from eight normoglycemic control subjects (body mass index, 29 ± 2 kg/m2) and eight type 2 diabetic patients (body mass index, 30 ± 1 kg/m2; fasting glucose, 14 ± 1 mm). In adipocytes isolated from diabetics, the basal 3-O-methylglucose transport rate was decreased by 50% compared with controls (7.1 ± 2.9 vs. 14.1 ± 3.7 mmol/mm2 surface area/min), and there was no increase in response to maximal insulin (7.9 ± 2.7 vs. 44.5 ± 9.2 in controls). In membrane subfractions from controls, insulin led to a marked increase of IRAP in the PM from 0.103 ± 0.04 to 1.00± 0.33 relative units/mg protein, concomitant with an 18% decrease in low-density microsomes and no change in high-density microsomes (HDM). In type 2 diabetes, IRAP overall expression in adipocytes was similar to that in controls; however, two abnormalities were observed. First, in basal cells, IRAP was redistributed away from low-density microsomes, and more IRAP was recovered in HDM (1.2-fold) and PM (4.4-fold) from diabetics compared with controls. Second, IRAP recruitment to PM by maximal insulin was markedly impaired. GLUT4 was depleted in all membrane subfractions (43–67%) in diabetes, and there was no increase in PM GLUT4 in response to insulin. Type 2 diabetes did not affect the fractionation of marker enzymes. We conclude that in human adipocytes: 1) IRAP is expressed and translocates to PM in response to insulin; 2) GLUT4 depletion involves all membrane subfractions in type 2 diabetes, although cellular levels of IRAP are normal; and 3) in type 2 diabetes, IRAP accumulates in membrane vesicles cofractionating with HDM and PM under basal conditions, and insulin-mediated recruitment to PM is impaired. Therefore, in type 2 diabetes, adipocytes express defects in trafficking of GLUT4/IRAP-containing vesicles similar to those causing insulin resistance in skeletal muscle.

scholarly journals Inhibitory effect of hyperglycemia on insulin-induced Akt/protein kinase B activation in skeletal muscle

2001 ◽  
Vol 280 (5) ◽  
pp. E816-E824 ◽  
Author(s):  
Akira Oku ◽  
Masao Nawano ◽  
Kiichiro Ueta ◽  
Takuya Fujita ◽  
Itsuro Umebayashi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Protein Kinase ◽  
Insulin Receptor ◽  
Soleus Muscle ◽  
Insulin Signaling ◽  
Skeletal Muscles ◽  
Glucose Transporter ◽  
Protein Kinase B ◽  
Diabetic Rats

To determine the molecular mechanism underlying hyperglycemia-induced insulin resistance in skeletal muscles, postreceptor insulin-signaling events were assessed in skeletal muscles of neonatally streptozotocin-treated diabetic rats. In isolated soleus muscle of the diabetic rats, insulin-stimulated 2-deoxyglucose uptake, glucose oxidation, and lactate release were all significantly decreased compared with normal rats. Similarly, insulin-induced phosphorylation and activation of Akt/protein kinase B (PKB) and GLUT-4 translocation were severely impaired. However, the upstream signal, including phosphorylation of the insulin receptor (IR) and insulin receptor substrate (IRS)-1 and -2 and activity of phosphatidylinositol (PI) 3-kinase associated with IRS-1/2, was enhanced. The amelioration of hyperglycemia by T-1095, a Na+-glucose transporter inhibitor, normalized the reduced insulin sensitivity in the soleus muscle and the impaired insulin-stimulated Akt/PKB phosphorylation and activity. In addition, the enhanced PI 3-kinase activation and phosphorylation of IR and IRS-1 and -2 were reduced to normal levels. These results suggest that sustained hyperglycemia impairs the insulin-signaling steps between PI 3-kinase and Akt/PKB, and that impaired Akt/PKB activity underlies hyperglycemia-induced insulin resistance in skeletal muscle.

scholarly journals Antcin K, a Triterpenoid Compound fromAntrodia camphorata, Displays Antidiabetic and Antihyperlipidemic Effects via Glucose Transporter 4 and AMP-Activated Protein Kinase Phosphorylation in Muscles

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Yueh-Hsiung Kuo ◽  
Cheng-Hsiu Lin ◽  
Chun-Ching Shih ◽  
Chang-Syun Yang
Keyword(s):  
Fatty Acid ◽  
Blood Glucose ◽  
Protein Kinase ◽  
Total Cholesterol ◽  
Fatty Acid Synthase ◽  
Glucose Transporter ◽  
Control Group ◽  
Mrna Levels ◽  
Glucose Transporter 4 ◽  
Amp Activated Protein Kinase

The purpose of this study was to screen firstly the potential effects of antcin K (AnK), the main constituent of the fruiting body ofAntrodia camphorata,in vitroand further evaluate the activities and mechanisms in high-fat-diet- (HFD-) induced mice. Following 8-week HFD-induction, mice were treated with AnK, fenofibrate (Feno), metformin (Metf), or vehicle for 4 weeks afterward. In C2C12 myotube cells, the membrane GLUT4 and phospho-Akt expressions were higher in insulin and AnK-treated groups than in the control group. It was observed that AnK-treated mice significantly lowered blood glucose, triglyceride, total cholesterol, and leptin levels in AnK-treated groups. Of interest, AnK at 40 mg/kg/day dosage displayed both antihyperglycemic effect comparable to Metf (300 mg/kg/day) and antihypertriglyceridemic effect comparable to Feno (250 mg/kg/day). The combination of significantly increased skeletal muscular membrane expression levels of glucose transporter 4 (GLUT4) but decreased hepatic glucose-6-phosphatase (G6 Pase) mRNA levels by AnK thus contributed to a decrease in blood glucose levels. Furthermore, AnK enhanced phosphorylation of AMP-activated protein kinase (phospho-AMPK) expressions in the muscle and liver. Moreover, AnK treatment exhibited inhibition of hepatic fatty acid synthase (FAS) but enhancement of fatty acid oxidation peroxisome proliferator-activated receptorα(PPARα) expression coincident with reduced sterol response element binding protein-1c (SREBP-1c) mRNA levels in the liver may contribute to decreased plasma triglycerides, hepatic steatosis, and total cholesterol levels. The present findings indicate that AnK displays an advantageous therapeutic potential for the management of type 2 diabetes and hyperlipidemia.

Regulation of glucose transporter and hexokinase II expression in tissues of diabetic rats

1993 ◽  
Vol 265 (3) ◽  
pp. E392-E401 ◽  
Author(s):  
R. Burcelin ◽  
R. L. Printz ◽  
J. Kande ◽  
R. Assan ◽  
D. K. Granner ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Blood Glucose ◽  
Blood Glucose Level ◽  
Glucose Transport ◽  
Glucose Level ◽  
Glucose Transporter ◽  
Diabetic Rats ◽  
Hexokinase Ii ◽  
Glut 4

Glucose transport and phosphorylation are decreased in muscle and adipose tissue in diabetes mellitus. The glucose transporter GLUT-4 and hexokinase II (HK II) are the main isoforms of proteins involved in glucose transport and phosphorylation in insulin-sensitive tissues, adipose tissue, skeletal muscle, and heart. The molecular mechanisms responsible for the decrease of glucose transport and phosphorylation have been studied during the first 3 days after streptozotocin (STZ) administration in adult male Wistar rats. GLUT-4 mRNA and protein and HK II mRNA and enzyme activity were measured. After the injection of STZ (30 h), GLUT-4 and HK II mRNAs were decreased to 10 +/- 1 and 20 +/- 3% that found in nondiabetic rats, respectively; they remained at these low levels for 72 h. Normalization of the blood glucose level by phlorizin infusion did not restore GLUT-4 and HK II mRNA concentrations to normal. In contrast, normalization of the blood glucose level by physiological infusion of insulin resulted in a total normalization of GLUT-4 and HK II mRNA concentrations. When insulin therapy was stopped, GLUT-4 and HK II mRNA and protein concentrations fell in 6 h to 40 and 20% of control levels, respectively. Minimal changes of GLUT-4 and HK II mRNA, and of HK II activity, were observed in skeletal muscle and heart of diabetic rats. We conclude that GLUT-4 and HK II mRNA are coordinately expressed in white adipose tissue. They are rapidly affected by an acute decrease of the plasma insulin concentrations but are not modified by hyperglycemia. In contrast, skeletal muscle and heart GLUT-4 and HK II mRNA are not greatly affected by short-term diabetes.

scholarly journals Potential Role of Protein Kinase B in Glucose Transporter 4 Translocation in Adipocytes*

Endocrinology ◽  
1997 ◽  
Vol 138 (5) ◽  
pp. 2005-2010 ◽  
Author(s):  
Jean-François Tanti ◽  
Sophie Grillo ◽  
Thierry Grémeaux ◽  
Paul J. Coffer ◽  
Emmanuel Van Obberghen ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cell Surface ◽  
Okadaic Acid ◽  
Potential Role ◽  
Glucose Transporter ◽  
Protein Kinase B ◽  
Glucose Transporter 4 ◽  
Glut 4 ◽  
Glut 4 Translocation

Abstract Phosphatidylinositol 3-kinase (PI 3-kinase) activation promotes glucose transporter 4 (Glut 4) translocation in adipocytes. In this study, we demonstrate that protein kinase B, a serine/threonine kinase stimulated by PI 3-kinase, is activated by both insulin and okadaic acid in isolated adipocytes, in parallel with their effects on Glut 4 translocation. In 3T3-L1 adipocytes, platelet-derived growth factor activated PI 3-kinase as efficiently as insulin but was only half as potent as insulin in promoting protein kinase B (PKB) activation. To look for a potential role of PKB in Glut 4 translocation, adipocytes were transfected with a constitutively active PKB (Gag-PKB) together with an epitope tagged transporter (Glut 4 myc). Gag-PKB was associated with all membrane fractions, whereas the endogenous PKB was mostly cytosolic. Expression of Gag-PKB led to an increase in Glut 4 myc amount at the cell surface. Our results suggest that PKB could play a role in promoting Glut 4 appearance at the cell surface following exposure of adipocytes to insulin and okadaic acid stimulation.

scholarly journals Antidiabetic and Antihyperlipidemic Effects ofClitocybe nudaon Glucose Transporter 4 and AMP-Activated Protein Kinase Phosphorylation in High-Fat-Fed Mice

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Mei-Hsing Chen ◽  
Cheng-Hsiu Lin ◽  
Chun-Ching Shih
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Glucose Transporter ◽  
Body Weight Gain ◽  
Glucose Production ◽  
Hypolipidemic Effect ◽  
Glucose Transporter 4 ◽  
High Fat ◽  
Hepatic Expression ◽  
Amp Activated Protein Kinase

The objective of this study was to evaluate the antihyperlipidemic and antihyperglycemic effects and mechanism of the extract ofClitocybe nuda(CNE), in high-fat- (HF-) fed mice. C57BL/6J was randomly divided into two groups: the control (CON) group was fed with a low-fat diet, whereas the experimental group was fed with a HF diet for 8 weeks. Then, the HF group was subdivided into five groups and was given orally CNE (including C1: 0.2, C2: 0.5, and C3: 1.0 g/kg/day extracts) or rosiglitazone (Rosi) or vehicle for 4 weeks. CNE effectively prevented HF-diet-induced increases in the levels of blood glucose, triglyceride, insulin (P<0.001,P<0.01,P<0.05, resp.) and attenuated insulin resistance. By treatment with CNE, body weight gain, weights of white adipose tissue (WAT) and hepatic triacylglycerol content were reduced; moreover, adipocytes in the visceral depots showed a reduction in size. By treatment with CNE, the protein contents of glucose transporter 4 (GLUT4) were significantly increased in C3-treated group in the skeletal muscle. Furthermore, CNE reduces the hepatic expression of glucose-6-phosphatase (G6Pase) and glucose production. CNE significantly increases protein contents of phospho-AMP-activated protein kinase (AMPK) in the skeletal muscle and adipose and liver tissues. Therefore, it is possible that the activation of AMPK by CNE leads to diminished gluconeogenesis in the liver and enhanced glucose uptake in skeletal muscle. It is shown that CNE exhibits hypolipidemic effect in HF-fed mice by increasing ATGL expression, which is known to help triglyceride to hydrolyze. Moreover, antidiabetic properties of CNE occurred as a result of decreased hepatic glucose production via G6Pase downregulation and improved insulin sensitization. Thus, amelioration of diabetic and dyslipidemic states by CNE in HF-fed mice occurred by regulation of GLUT4, G6Pase, ATGL, and AMPK phosphorylation.

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