scholarly journals Effect of Sucralose on Glucose Uptake in Rat L6 Myotubes

2017 ◽  
Vol 21 (2) ◽  
pp. 162-165
Author(s):  
Shubha N Prakash ◽  
Jayakumari Shanthakumari ◽  
Anitha Devanath
Keyword(s):  
Insulin Resistance ◽  
Cell Culture ◽  
Glucose Uptake ◽  
Cell Line ◽  
Artificial Sweeteners ◽  
Public Concern ◽  
Insulin Stimulation ◽  
L6 Myotubes ◽  
Sugar Levels ◽  
Basal Glucose Uptake

ABSTRACT Introduction With growing awareness of the link between diet and health and the problem of obesity, public concern over sugar levels in the diet is forcing a worldwide trend toward cutting down on sugar by using artificial sweeteners (AS). Aim To study the effect of increasing concentrations of sucralose (an AS) on glucose uptake in rat L6 myotubes. Materials and methods The L6 cell line from American type cell culture (ATCC) was grown in Dulbecco's Modified Eagle's Medium (DMEM) and differentiated into myotubes. The wells were exposed to either 0, 1 nM, 1 μM, or 1 mM of sucralose alone or with 10 nM insulin for 24 hours. Glucose uptake was studied after this period. Results Significant decrease was seen between the insulin-stimulated basal glucose uptake and insulin-stimulated glucose uptake across all the concentrations of sucralose treatment. Conclusion Increased concentration of sucralose appears to decrease glucose uptake even on insulin stimulation. Clinical significance It may not be beneficial to use sucralose in certain groups of people who have insulin resistance or are prone to it. How to cite this article Prakash SN, Shanthakumari J, Devanath A. Effect of Sucralose on Glucose Uptake in Rat L6 Myotubes. Indian J Med Biochem 2017;21(2):162-165.

DAG accumulation from saturated fatty acids desensitizes insulin stimulation of glucose uptake in muscle cells

2001 ◽  
Vol 280 (2) ◽  
pp. E229-E237 ◽  
Author(s):  
Eulàlia Montell ◽  
Marco Turini ◽  
Mario Marotta ◽  
Matthew Roberts ◽  
Véronique Noé ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Glucose Uptake ◽  
Insulin Response ◽  
Insulin Stimulation ◽  
Kinase C ◽  
Basal Glucose Uptake ◽  
Stimulation Of

The increased availability of saturated lipids has been correlated with development of insulin resistance, although the basis for this impairment is not defined. This work examined the interaction of saturated and unsaturated fatty acids (FA) with insulin stimulation of glucose uptake and its relation to the FA incorporation into different lipid pools in cultured human muscle. It is shown that basal or insulin-stimulated 2-deoxyglucose uptake was unaltered in cells preincubated with oleate, whereas basal glucose uptake was increased and insulin response was impaired in palmitate- and stearate-loaded cells. Analysis of the incorporation of FA into different lipid pools showed that palmitate, stearate, and oleate were similarly incorporated into phospholipids (PL) and did not modify the FA profile. In contrast, differences were observed in the total incorporation of FA into triacylglycerides (TAG): unsaturated FA were readily diverted toward TAG, whereas saturated FA could accumulate as diacylglycerol (DAG). Treatment with palmitate increased the activity of membrane-associated protein kinase C, whereas oleate had no effect. Mixture of palmitate with oleate diverted the saturated FA toward TAG and abolished its effect on glucose uptake. In conclusion, our data indicate that saturated FA-promoted changes in basal glucose uptake and insulin response were not correlated to a modification of the FA profile in PL or TAG accumulation. In contrast, these changes were related to saturated FA being accumulated as DAG and activating protein kinase C. Therefore, our results suggest that accumulation of DAG may be a molecular link between an increased availability of saturated FA and the induction of insulin resistance.

Saturated, but not n-6 polyunsaturated, fatty acids induce insulin resistance: role of intramuscular accumulation of lipid metabolites

2006 ◽  
Vol 100 (5) ◽  
pp. 1467-1474 ◽  
Author(s):  
Jong Sam Lee ◽  
Srijan K. Pinnamaneni ◽  
Su Ju Eo ◽  
In Ho Cho ◽  
Jae Hwan Pyo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acids ◽  
Insulin Sensitivity ◽  
Polyunsaturated Fatty Acids ◽  
Glucose Uptake ◽  
High Fat ◽  
Insulin Resistant ◽  
L6 Myotubes ◽  
Lipid Metabolites

Consumption of a Western diet rich in saturated fats is associated with obesity and insulin resistance. In some insulin-resistant phenotypes this is associated with accumulation of skeletal muscle fatty acids. We examined the effects of diets high in saturated fatty acids (Sat) or n-6 polyunsaturated fatty acids (PUFA) on skeletal muscle fatty acid metabolite accumulation and whole-body insulin sensitivity. Male Sprague-Dawley rats were fed a chow diet (16% calories from fat, Con) or a diet high (53%) in Sat or PUFA for 8 wk. Insulin sensitivity was assessed by fasting plasma glucose and insulin and glucose tolerance via an oral glucose tolerance test. Muscle ceramide and diacylglycerol (DAG) levels and triacylglycerol (TAG) fatty acids were also measured. Both high-fat diets increased plasma free fatty acid levels by 30%. Compared with Con, Sat-fed rats were insulin resistant, whereas PUFA-treated rats showed improved insulin sensitivity. Sat caused a 125% increase in muscle DAG and a small increase in TAG. Although PUFA also resulted in a small increase in DAG, the excess fatty acids were primarily directed toward TAG storage (105% above Con). Ceramide content was unaffected by either high-fat diet. To examine the effects of fatty acids on cellular lipid storage and glucose uptake in vitro, rat L6 myotubes were incubated for 5 h with saturated and polyunsaturated fatty acids. After treatment of L6 myotubes with palmitate (C16:0), the ceramide and DAG content were increased by two- and fivefold, respectively, concomitant with reduced insulin-stimulated glucose uptake. In contrast, treatment of these cells with linoleate (C18:2) did not alter DAG, ceramide levels, and glucose uptake compared with controls (no added fatty acids). Both 16:0 and 18:2 treatments increased myotube TAG levels (C18:2 vs. C16:0, P < 0.05). These results indicate that increasing dietary Sat induces insulin resistance with concomitant increases in muscle DAG. Diets rich in n-6 PUFA appear to prevent insulin resistance by directing fat into TAG, rather than other lipid metabolites.

scholarly journals Attenuation of Free Fatty Acid-Induced Muscle Insulin Resistance by Rosemary Extract

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1623 ◽  
Author(s):  
Filip Vlavcheski ◽  
Evangelia Tsiani
Keyword(s):  
Insulin Resistance ◽  
Glucose Uptake ◽  
Muscle Cell ◽  
Serine Phosphorylation ◽  
Rosemary Extract ◽  
Muscle Insulin Resistance ◽  
Insulin Resistant ◽  
L6 Myotubes ◽  
P70 S6k ◽  
Amp Activated Protein Kinase

Elevated blood free fatty acids (FFAs), as seen in obesity, impair muscle insulin action leading to insulin resistance and Type 2 diabetes mellitus. Serine phosphorylation of the insulin receptor substrate (IRS) is linked to insulin resistance and a number of serine/threonine kinases including JNK, mTOR and p70 S6K have been implicated in this process. Activation of the energy sensor AMP-activated protein kinase (AMPK) increases muscle glucose uptake, and in recent years AMPK has been viewed as an important target to counteract insulin resistance. We reported recently that rosemary extract (RE) increased muscle cell glucose uptake and activated AMPK. However, the effect of RE on FFA-induced muscle insulin resistance has never been examined. In the current study, we investigated the effect of RE in palmitate-induced insulin resistant L6 myotubes. Exposure of myotubes to palmitate reduced the insulin-stimulated glucose uptake, increased serine phosphorylation of IRS-1, and decreased the insulin-stimulated phosphorylation of Akt. Importantly, exposure to RE abolished these effects and the insulin-stimulated glucose uptake was restored. Treatment with palmitate increased the phosphorylation/activation of JNK, mTOR and p70 S6K whereas RE completely abolished these effects. RE increased the phosphorylation of AMPK even in the presence of palmitate. Our data indicate that rosemary extract has the potential to counteract the palmitate-induced muscle cell insulin resistance and further studies are required to explore its antidiabetic properties.

scholarly journals Reduction of Insulin-Stimulated Glucose Uptake in L6 Myotubes by the Protein Kinase Inhibitor SB203580 Is Independent of p38MAPK Activity

Endocrinology ◽  
2005 ◽  
Vol 146 (9) ◽  
pp. 3773-3781 ◽  
Author(s):  
C. N. Antonescu ◽  
C. Huang ◽  
W. Niu ◽  
Z. Liu ◽  
P. A. Eyers ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Kinase Inhibitor ◽  
Dominant Negative ◽  
Small Interfering Rnas ◽  
Insulin Stimulation ◽  
L6 Myotubes ◽  
Low Levels ◽  
Glucose Transporter Glut4

Abstract Insulin increases glucose uptake through translocation of the glucose transporter GLUT4 to the plasma membrane. We previously showed that insulin activates p38MAPK, and inhibitors of p38MAPKα and p38MAPKβ (e.g. SB203580) reduce insulin-stimulated glucose uptake without affecting GLUT4 translocation. This observation suggested that insulin may increase GLUT4 activity via p38α and/or p38β. Here we further explore the possible participation of p38MAPK through a combination of molecular strategies. SB203580 reduced insulin stimulation of glucose uptake in L6 myotubes overexpressing an SB203580-resistant p38α (drug-resistant p38α) but barely affected phosphorylation of the p38 substrate MAPK-activated protein kinase-2. Expression of dominant-negative p38α or p38β reduced p38MAPK phosphorylation by 70% but had no effect on insulin-stimulated glucose uptake. Gene silencing via isoform-specific small interfering RNAs reduced expression of p38α or p38β by 60–70% without diminishing insulin-stimulated glucose uptake. SB203580 reduced photoaffinity labeling of GLUT4 by bio-LC-ATB-BMPA only in the insulin-stimulated state. Unless low levels of p38MAPK suffice to regulate glucose uptake, these results suggest that the inhibition of insulin-stimulated glucose transport by SB203580 is likely not mediated by p38MAPK. Instead, changes experienced by insulin-stimulated GLUT4 make it susceptible to inhibition by SB203580.

1147-P: Pseudo Insulin Resistance: Palmitate Inactivates Insulin Signaling but Stimulates Basal Glucose Uptake in 3T3-L1 Adipocytes

Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 1147-P
Author(s):  
NIKITA PODKUYCHENKO ◽  
SVETLANA MICHURINA ◽  
IURII STAFEEV ◽  
ASKER Y. KHAPCHAEV ◽  
VLADIMIR P. SHIRINSKY ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Uptake ◽  
Insulin Signaling ◽  
Basal Glucose Uptake

scholarly journals Fenofibrate Reverses Palmitate Induced Impairment in Glucose Uptake in Skeletal Muscle Cells by Preventing Cytosolic Ceramide Accumulation

2015 ◽  
Vol 37 (4) ◽  
pp. 1315-1328 ◽  
Author(s):  
Sudarshan Bhattacharjee ◽  
Nabanita Das ◽  
Ashok Mandala ◽  
Satinath Mukhopadhyay ◽  
Sib Sankar Roy
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Glucose Uptake ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
Stoichiometric Ratio ◽  
Mrna Levels ◽  
L6 Myotubes ◽  
Hypolipidemic Agents ◽  
Ceramide Accumulation

Backgrounds/Aims: The lipid induced insulin resistance is a major pathophysiologic mechanism underlying glucose intolerance of varying severity. PPARα-agonists are proven as effective hypolipidemic agents. The aim of this study was to see if impaired glucose uptake in palmitate treated myotubes is reversed by fenofibrate. Methods: Palmitate-treated myotubes were used as a model for insulin resistance, impaired glucose uptake, fatty acid oxidation and ceramide synthesis. mRNA levels of CPT1 and CPT2 were determined by PCR array and Q-PCR. Results: The incubation of myotubes with 750 uM palmitate not only reduced glucose uptake but also impaired fatty acid oxidation and cytosolic ceramide accumulation. Palmitate upregulated CPT1b expression in L6 myotubes, while CPT2 expression level remained unchanged. The altered stoichiometric ratio between the two CPT isoforms led to reduced fatty acid oxidation (FAO), ceramide accumulation and impaired glucose uptake, whereas administration of 200 µM fenofibrate signifcantly reversed the above abnormalities by increasing CPT2 mRNA levels and restoring CPT1b to CPT2 ratio. Conclusion: Palmitate-induced alteration in the stoichiometric ratio of mitochondrial CPT isoforms leads to incomplete FAO and enhanced cytosolic ceramide accumulation that lead to insulin resistance. Fenofibrate ameliorated insulin resistance by restoring the altered stoichiometry by upregulating CPT2 and preventing, cytoplasmic ceramide accumulation.

scholarly journals Depletion of Branched-Chain Ketoacid Dehydrogenase Kinase (BDK) Upregulates Insulin-Stimulated Glucose Uptake in Muscle Cells

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 511-511
Author(s):  
Gagandeep Mann
Keyword(s):  
Insulin Resistance ◽  
Amino Acids ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Negative Regulator ◽  
Funding Sources ◽  
L6 Myotubes ◽  
Transport Assay ◽  
Branched Chain ◽  
Ketoacid Dehydrogenase

Abstract Objectives Plasma levels of branched-chain amino acids (BCAAs) and their metabolites, branched-chain ketoacids (BCKAs) are increased in insulin resistance, a condition that can lead to type 2 diabetes mellitus (T2DM). BCAA catabolic enzymes are downregulated in diabetes and obesity. We previously showed that leucine and KIC suppressed insulin-stimulated glucose uptake in L6 myotubes. We have also shown that knocking down branched-chain ketoacid dehydrogenase (BCKD), an enzyme that decarboxylates BCKAs, suppressed insulin-stimulated glucose uptake. The objective of this study is to analyze how stimulating BCAA catabolic flux, by depleting branched-chain ketoacid dehydrogenase kinase (BDK), a negative regulator of BCKD, affects insulin sensitivity. We hypothesize that upregulating BCAA catabolism will increase insulin-stimulated glucose transport and attenuate insulin resistance. Methods L6 myoblasts were cultured in differentiation media for 4 days. On day 4 of differentiation, cells were transfected with control (SCR) or branched-chain ketoacid dehydrogenase kinase (BDK) siRNA oligonucleotides. Forty-eight hours later, myotubes were starved of serum- and amino acids for 3 hours then supplemented with or without KIC (200 mM) for 30 minutes. After, cells were incubated with or without insulin (100 nM) for 20 minutes. They were then harvested for immunoblotting or used for glucose transport assay. Results There was a 32% increase in insulin-stimulated glucose uptake with BDK depletion. KIC suppressed insulin-stimulated glucose uptake by 25% in control (SCR) cells; this suppression was attenuated in cells depleted of BDK. BDK depletion also reduced KIC-induced IRS-1Ser612 phosphorylation by 64% but had no effect on AktSer473 phosphorylation. Conclusions BDK depletion increased insulin-stimulated glucose transport, and attenuated KIC-induced suppression of insulin-stimulated glucose uptake, suggesting that increasing BCKD activity can be a therapeutic strategy against insulin resistance. Funding Sources Natural Science and Research Council (NSERC)

scholarly journals Leukocyte antigen-related inhibition attenuates palmitate-induced insulin resistance in muscle cells

2012 ◽  
Vol 215 (1) ◽  
pp. 71-77 ◽  
Author(s):  
Sattar Gorgani-Firuzjaee ◽  
Salar Bakhtiyari ◽  
Abolfazl Golestani ◽  
Reza Meshkani
Keyword(s):  
Insulin Resistance ◽  
Glucose Uptake ◽  
Cell Line ◽  
C2c12 Cell ◽  
Muscle Cells ◽  
C2c12 Cells ◽  
Stable Cell Line ◽  
Protein Levels ◽  
Induce Insulin Resistance ◽  
And Control

Palmitate has been shown to induce insulin resistance in skeletal muscle cells. The aim of this study was to investigate the role of the leukocyte common antigen-related (LAR) gene in palmitate-induced insulin resistance in C2C12 cells. A stable C2C12 cell line was generated using LAR short hairpin RNA. The levels of LAR protein and phosphorylation of insulin receptor substrate-1 (IRS1) and Akt were detected by western blot analysis. 2-Deoxyglucose uptake was measured in LAR knockdown and control cells using d-[2-3H]glucose. LAR protein level was decreased by 65% in the stable cell line compared with the control cells. Palmitate (0.5 mM) significantly induced LAR mRNA (65%) and protein levels (40%) in myotubes compared with untreated cells. Palmitate significantly reduced insulin-stimulated glucose uptake in both the control and LAR knockdown cells by 33 and 51% respectively. However, LAR depletion improved insulin-stimulated glucose uptake in myotubes treated with palmitate. Furthermore, the inhibition of LAR prevented palmitate-induced decreases in phosphorylation of IRS1Tyr632 and AktSer473 in C2C12 cells. In conclusion, these results reveal that palmitate induces LAR expression in C2C12 cells. We also provided evidence that the inhibition of LAR attenuates palmitate-induced insulin resistance in myotubes.

Reversal of Insulin Resistance by ATP in Hemorrhagic Shock

1975 ◽  
Vol 53 (5) ◽  
pp. 859-865 ◽  
Author(s):  
Irshad H. Chaudry ◽  
Mohammed M. Sayeed ◽  
Arthur E. Baue
Keyword(s):  
Insulin Resistance ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Hemorrhagic Shock ◽  
Glucose Uptake ◽  
Insulin Concentration ◽  
Insulin Effect ◽  
Intracellular Atp ◽  
Basal Glucose Uptake ◽  
Stimulation Of

Hemorrhagic shock was produced by bleeding rats to a mean arterial pressure of 40 mm Hg (1 mm Hg = 133 N/m2), which was maintained for 2 h. Muscles from these animals ('shock' muscles) showed resistance to the stimulation of glucose uptake by insulin. Addition of 1 mM ATP–MgCl2 to the medium had no effect on basal glucose uptake in either group of muscles, but it permitted insulin to exert its stimulatory effect in 'shock' muscles. An optimal insulin effect on glucose uptake in 'shock' muscles incubated without ATP was observed at an insulin concentration of 0.2 Unit/ml. When 1 mM ATP–MgCl2 was added to the medium, optimal insulin effect in 'shock' muscles was observed at an insulin concentration of 0.007 Unit/ml. Increasing the concentration of ATP–MgCl2 to 2.5 mM in the medium resulted in an optimal insulin effect at an insulin concentration of 0.001 Unit/ml in 'shock' muscles. Following 1 h incubation in Krebs–HCO3 medium, intracellular ATP contents of 'shock' muscles were approximately 50% lower than in control muscles. Addition of 1 mM ATP–MgCl2 to the incubation medium had no effect on the intracellular ATP contents of either group of muscles following incubation; however, 2.5 mM ATP–MgCl2 elevated intracellular ATP contents of 'shock' muscles but had no effect in control muscles. Possible mechanisms for this reversal of insulin resistance by ATP-MgCl2 in shock are discussed.

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