scholarly journals Stevioside Attenuates Insulin Resistance in Skeletal Muscle by Facilitating IR/IRS-1/Akt/GLUT 4 Signaling Pathways: An In Vivo and In Silico Approach

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7689
Author(s):  
Abilasha Deenadayalan ◽  
Vijayalakshmi Subramanian ◽  
Vijayalakshmi Paramasivan ◽  
Vishnu Priya Veeraraghavan ◽  
Gayathri Rengasamy ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Insulin Receptor ◽  
Lipid Profile ◽  
Insulin Signaling ◽  
In Silico ◽  
Gastrocnemius Muscle ◽  
Glut 4 ◽  
Gastrocnemius Muscles

Type-2 diabetes mellitus (T2DM), the leading global health burden of this century majorly develops due to obesity and hyperglycemia-induced oxidative stress in skeletal muscles. Hence, developing novel drugs that ameliorate these pathological events is an immediate priority. The study was designed to analyze the possible role of Stevioside, a characteristic sugar from leaves of Stevia rebaudiana (Bertoni) on insulin signaling molecules in gastrocnemius muscle of obesity and hyperglycemia-induced T2DM rats. Adult male Wistar rats rendered diabetic by administration of high fat diet (HFD) and sucrose for 60 days were orally administered with SIT (20 mg/kg/day) for 45 days. Various parameters were estimated including fasting blood glucose (FBG), serum lipid profile, oxidative stress markers, antioxidant enzymes and expression of insulin signaling molecules in diabetic gastrocnemius muscle. Stevioside treatment improved glucose and insulin tolerances in diabetic rats and restored their elevated levels of FBG, serum insulin and lipid profile to normalcy. In diabetic gastrocnemius muscles, Setvioside normalized the altered levels of lipid peroxidase (LPO), hydrogen peroxide (H2O2) and hydroxyl radical (OH*), antioxidant enzymes (CAT, SOD, GPx and GSH) and molecules of insulin signaling including insulin receptor (IR), insulin receptor substrate-1 (IRS-1) and Akt mRNA levels. Furthermore, Stevioside enhanced glucose uptake (GU) and oxidation in diabetic muscles by augmenting glucose transporter 4 (GLUT 4) synthesis very effectively in a similar way to metformin. Results of molecular docking analysis evidenced the higher binding affinity with IRS-1 and GLUT 4. Stevioside effectively inhibits oxidative stress and promotes glucose uptake in diabetic gastrocnemius muscles by activating IR/IRS-1/Akt/GLUT 4 pathway. The results of the in silico investigation matched those of the in vivo study. Hence, Stevioside could be considered as a promising phytomedicine to treat T2DM.

scholarly journals Canthin-6-one ameliorates TNBS-induced colitis in rats by modulating inflammation and oxidative stress. An in vivo and in silico approach

2021 ◽  
Vol 186 ◽  
pp. 114490
Author(s):  
Karuppusamy Arunachalam ◽  
Amilcar Sabino Damazo ◽  
Antonio Macho ◽  
Monica Steffi Matchado ◽  
Eduarda Pavan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
In Silico ◽  
And Oxidative Stress

Regulation of glucose transporter GLUT-4 and hexokinase II gene transcription by insulin and epinephrine

1997 ◽  
Vol 273 (4) ◽  
pp. E682-E687 ◽  
Author(s):  
Jared P. Jones ◽  
G. Lynis Dohm
Keyword(s):  
Skeletal Muscle ◽  
Gene Transcription ◽  
Glucose Transporter ◽  
Male Rats ◽  
Rat Skeletal Muscle ◽  
Hexokinase Ii ◽  
Epinephrine Infusion ◽  
Glut 4 ◽  
Gastrocnemius Muscles

Transport of glucose across the plasma membrane by GLUT-4 and subsequent phosphorylation of glucose by hexokinase II (HKII) constitute the first two steps of glucose utilization in skeletal muscle. This study was undertaken to determine whether epinephrine and/or insulin regulates in vivo GLUT-4 and HKII gene transcription in rat skeletal muscle. In the first experiment, adrenodemedullated male rats were fasted 24 h and killed in the control condition or after being infused for 1.5 h with epinephrine (30 μg/ml at 1.68 ml/h). In the second experiment, male rats were fasted 24 h and killed after being infused for 2.5 h at 1.68 ml/h with saline or glucose (625 mg/ml) or insulin (39.9 μg/ml) plus glucose (625 mg/ml). Nuclei were isolated from pooled quadriceps, tibialis anterior, and gastrocnemius muscles. Transcriptional run-on analysis indicated that epinephrine infusion decreased GLUT-4 and increased HKII transcription compared with fasted controls. Both glucose and insulin plus glucose infusion induced increases in GLUT-4 and HKII transcription of twofold and three- to fourfold, respectively, compared with saline-infused rats. In conclusion, epinephrine and insulin may regulate GLUT-4 and HKII genes at the level of transcription in rat skeletal muscle.

Genistein and Momordica charantia L. prevents oxidative stress and upregulate proglucagon and insulin receptor mRNA in diabetic rats.

2021 ◽  
Author(s):  
Wusa Makena ◽  
Abdullahi Ibrahim Iliya ◽  
Joseph Olajide Hambolu ◽  
James Abrak Timbuak ◽  
Uduak Emmanuel Umana ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Insulin Receptor ◽  
Mrna Expression ◽  
Insulin Signaling ◽  
Diabetic Rats ◽  
Momordica Charantia ◽  
Receptor Mrna ◽  
Group I

Type 2 diabetes (T2D) occur as a result of insulin resistance and malfunction in insulin signaling. Controlling hyperglycemia and activation of insulin signaling are important in the management of T2D. The study aimed to evaluate the effect of Genistein and Momordica charantia L. fruit on oxidative stress, markers of inflammation, and their role on proglucagon and insulin receptor mRNA expression by RT-PCR in diabetic rats. Thirty-five albino rats were divided into seven groups (n=5). Group I (non-diabetic) and group II (diabetic control) were treated with distilled water, groups III and IV received 250mg/kg and 500mg/kg lyophilized MCF respectively. Groups V and VI received 10mg/kg and 20mg/kg Genistein respectively while group VII received 500mg/kg Metformin. The administration lasted for 28 days. MCF and Genistein significantly reduced IL-1β and TNFα levels that was elevated in serum of diabetic rats. Treatment with MCF and Genistein significant increased the expression of proglucagon mRNA in the small intestine and insulin receptor mRNA in the liver of diabetic rats. In conclusion, MCF and Genistein ameliorate type 2 diabetes complications by preventing the loss of insulin-positive cells, inhibiting IL-1β and TNFα and up-regulating proglucagon and insulin receptor mRNA expression. Novelty: • MCF and Genistein has an inhibitory effect on diabetic induced IL-1β and TNFα production. • MCF and Genistein up-regulates proglucagon and insulin receptor mRNA expression.

scholarly journals Gosha-jinki-gan (a Herbal Complex) Corrects Abnormal Insulin Signaling

2004 ◽  
Vol 1 (3) ◽  
pp. 269-276 ◽  
Author(s):  
Bolin Qin ◽  
Masaru Nagasaki ◽  
Ming Ren ◽  
Gustavo Bajotto ◽  
Yoshiharu Oshida ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Receptor ◽  
Protein Content ◽  
Insulin Signaling ◽  
Molecular Mechanisms ◽  
Diabetic Rats ◽  
Metabolic Clearance ◽  
Long Term Effects ◽  
Β Protein

Previous studies have shown that the traditional herbal complex Gosha-jinki-gan (GJG) improves diabetic neuropathy and insulin resistance. The present study was undertaken to elucidate the molecular mechanisms related with the long-term effects of GJG administration on insulin actionin vivoand the early steps of insulin signaling in skeletal muscle in streptozotocin (STZ) diabetes. Rats were randomized into five subgroups: (1) saline treated control, (2) GJG treated control, (3) 2-unit insulin + saline treated diabetic, (4) saline + GJG treated diabetic and (5) 2-unit insulin + GJG treated diabetic groups. After seven days of treatment, euglycemic clamp experiment at an insulin infusion rate of 6 mU/kg/min was performed in overnight fasted rats. Despite the 2-unit insulin treatment, the metabolic clearance rates of glucose (MCR, ml/kg/min) in diabetic rats were significantly lower compared with the controls (11.4 ± 1.0 vs 44.1 ± 1.5;P< 0.001), and were significantly improved by insulin combined with GJG or GJG alone (26 ± 3.2 and 24.6 ± 2.2,P< 0.01, respectively). The increased insulin receptor (IR)-β protein content in skeletal muscle of diabetic rats was not affected by insulin combined with GJG administration. However, the decreased insulin receptor substrate-1 (IRS-1) protein content was significantly improved by treatment with GJG. Additionally, the increased tyrosine phosphorylation levels of IR-β and IRS-1 were significantly inhibited in insulin combined with GJG treated diabetes. The present results suggest that the improvement of the impaired insulin sensitivity in STZ-diabetic rats by administration of GJG may be due, at least in part, to correction in the abnormal early steps of insulin signaling in skeletal muscle.

Effect of in vivo injection of cholera and pertussis toxin on glucose transport in rat skeletal muscle

1997 ◽  
Vol 272 (1) ◽  
pp. E7-E17 ◽  
Author(s):  
T. Ploug ◽  
X. Han ◽  
L. N. Petersen ◽  
H. Galbo
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
Pertussis Toxin ◽  
Plasma Catecholamines ◽  
Plasma Free Fatty Acid ◽  
Glut 1 ◽  
Glut 4 ◽  
Gastrocnemius Muscles ◽  
Muscle Glucose Transport

Cholera toxin (CTX) and pertussis toxin (PTX) were examined for their ability to inhibit glucose transport in perfused skeletal muscle. Twenty-five hours after an intravenous injection of CTX, basal transport was decreased approximately 30%, and insulin- and contraction-stimulated transport was reduced at least 86 and 49%, respectively, in both the soleus and red and white gastrocnemius muscles. In contrast, PTX treatment was much less efficient. Impairment of glucose transport appeared to develop 10-15 h after CTX administration, which coincided with development of hyperglycemia despite hyperinsulinimia, increased plasma free fatty acid levels, increased adenosine 3',5'-cyclic monophosphate (cAMP) concentrations in muscle, but no difference in plasma catecholamines. Twenty-five hours after CTX treatment, GLUT-4 protein in both soleus and red gastrocnemius muscles was decreased, whereas no change in GLUT-1 protein content was found. In contrast, GLUT-4 mRNA was unchanged, but transcripts for GLUT-1 were increased > or = 150% in all three muscles from CTX-treated rats. The findings suggest that CTX via increased cAMP impairs basal as well as insulin- and contraction-stimulated muscle glucose transport, at least in part from a decrease in intramuscular GLUT-4 protein.

Exercise-associated differences in an array of proteins involved in signal transduction and glucose transport

2001 ◽  
Vol 90 (1) ◽  
pp. 29-34 ◽  
Author(s):  
Mei Yu ◽  
Eva Blomstrand ◽  
Alexander V. Chibalin ◽  
Harriet Wallberg-Henriksson ◽  
Juleen R. Zierath ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Protein Kinase ◽  
Insulin Receptor ◽  
Insulin Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Signaling Cascade ◽  
Vastus Lateralis Muscle ◽  
Glut 4 ◽  
Mitogen Activated Protein ◽  
Kinase Expression

Vastus lateralis muscle biopsies were obtained from endurance-trained (running ∼50 km/wk) and untrained (no regular physical exercise) men, and the expression of an array of insulin-signaling intermediates was determined. Expression of insulin receptor and insulin receptor substrate-1 and -2 was decreased 44% ( P < 0.05), 57% ( P < 0.001), and 77% ( P < 0.001), respectively, in trained vs. untrained muscle. The downstream signaling target, Akt kinase, was not altered in trained subjects. Components of the mitogenic signaling cascade were also assessed. Extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase expression was 190% greater ( P < 0.05), whereas p38 mitogen-activated protein kinase expression was 32% lower ( P < 0.05), in trained vs. untrained muscle. GLUT-4 protein expression was twofold higher ( P < 0.05), and the GLUT-4 vesicle-associated protein, the insulin-regulated aminopeptidase, was increased 4.7-fold ( P < 0.05) in trained muscle. In conclusion, the expression of proteins involved in signal transduction is altered in skeletal muscle from well-trained athletes. Downregulation of early components of the insulin-signaling cascade may occur in response to increased insulin sensitivity associated with endurance training.

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