Isoalantolactone derivative promotes glucose utilization in skeletal muscle cells and increases energy expenditure in db/db mice via activating AMPK-dependent signaling

Arha, Deepti; Ramakrishna, E.; Gupta, Anand P.; Amit, K.; Sharma, Aditya; Ahmad, Ishbal; Riyazuddin, Mohammed; Gayen, Jiaur R.; Maurya, Rakesh; Tamrakar, Akhilesh K.

doi:10.1016/j.mce.2017.07.015

Cited by 19 publications

(13 citation statements)

References 56 publications

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“…Furthermore, it is the most abundant tissue in the whole body and thus, the proper function of skeletal tissue is important to maintain normal blood glucose levels. In fact, L6 cells represent a good model for glucose uptake because they have been used extensively to elucidate the mechanisms of glucose uptake in muscle, have an intact insulin signalling pathway and express the insulin-sensitive GLUT4 31 . Based on our findings showed that root extract displays a better activity with the increased stimulation of the 2-NBDG uptake in both of the cell lines as compared with fruit extract.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory evaluation ofCurculigo latifoliaon α-glucosidase, DPP (IV) andin vitrostudies in antidiabetic with molecular docking relevance to type 2 diabetes mellitus

Zabidi

Ishak

Hamid

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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The inhibition of a-glucosidase and DPP enzymes capable of effectively reducing blood glucose level in the management of type 2 diabetes. The purpose of the present study is to evaluate the inhibitory potential of a-glucosidase and DPP (IV) activity including with the 2-NBDG uptake assay and insulin secretion activities through in vitro studies. The selected of active compounds obtained from the screening of compounds by LC-MS were docked with the targeted enzyme that involved in the mechanism of T2DM. From the results, root extracts displayed a better promising outcome in a-glucosidase (IC 50 2.72 ± 0.32) as compared with the fruit extracts (IC 50 3.87 ± 0.32). Besides, root extracts also displayed a better activity in the inhibition of DPP (IV), enhance insulin secretion and glucose uptake activity. Molecular docking results revealing that phlorizin binds strongly with a-glucosidase, DPP (IV) and Insulin receptor (IR) enzymes with achieving the lowest binding energy value. The present work suggests several of the compounds have the potential that contribute towards inhibiting a-glucosidase and DPP (IV) and thus effective in lowering post-prandial hyperglycaemia.

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Section: Discussionmentioning

confidence: 99%

Inhibitory evaluation ofCurculigo latifoliaon α-glucosidase, DPP (IV) andin vitrostudies in antidiabetic with molecular docking relevance to type 2 diabetes mellitus

Zabidi

Ishak

Hamid

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Studies in isolated rat myocytes have shown that testosterone treatment increase the insulin responsive glucose transporter, Glut 4 translocation to plasma membrane of the skeletal muscle, resulting in increased glucose uptake by skeletal muscle cells [6]. Glut 4 translocation can be both insulin dependent and independent as certain bioactive molecules can increase Glut 4 translocation in skeletal muscle and testosterone activates Glut 4 translocation in 3T3-L1 adipocytes by stimulating the LKB1/AMPK pathway, in an insulin independent manner [7, 8]. However, in these studies, the underlying mechanism of action of testosterone on the insulin signaling pathway and insulin responsiveness in the major glucose homeostatic tissues, resulting in the enhanced glycemic control remained unanswered.…”

Section: Introductionmentioning

confidence: 99%

Testosterone supplementation improves insulin responsiveness in HFD fed male T2DM mice and potentiates insulin signaling in the skeletal muscle and C2C12 myocyte cell line

et al. 2019

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BackgroundType 2 Diabetes Mellitus (T2DM) is characterised by hyperglycemia due to the incidence of insulin resistance. Testosterone supplementation has been shown to have a positive co-relation with improved glycemic control in T2DM males. Clinical studies have reported that Androgen Replacement Therapy (ART) to hypogonadic males with T2DM resulted in improved glycemic control and metabolic parameters, but, these studies did not address in detail how testosterone acted on the key glucose homeostatic organs.MethodIn this study, we delineate the effect of testosterone supplementation to high-fat diet (HFD) induced T2DM in male C57BL6J mice and the effect of testosterone supplementation on the skeletal muscle insulin responsiveness. We also studied the effect of testosterone on the insulin signaling pathway proteins in C2C12 myocyte cells to validate the in vivo findings.ResultsWe found that testosterone had a potentiating effect on the skeletal muscle insulin signaling pathway to improve glycaemic control. We demonstrate that, in males, testosterone improves skeletal muscle insulin responsiveness by potentiating the PI3K-AKT pathway. The testosterone treated animals showed significant increase in the skeletal muscle Insulin Receptor (IR), p85 subunit of PI3K, P-GSK3α (Ser-21), and P-AKT (Ser-473) levels as compared to the control animals; but there was no significant change in total AKT and GSK3α. Testosterone supplementation inhibited GSK3α in the myocytes in a PI3K/AKT pathway dependent manner; on the other hand GSK3β gene expression was reduced in the skeletal muscle upon testosterone supplementation.ConclusionTestosterone increases insulin responsiveness by potentiating insulin signaling in the skeletal muscle cells, which is in contrast to the increased insulin resistance in the liver of testosterone treated T2DM male animals.

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“…The increase in triglyceride observed in some treated groups may probably be as a result of insufficient insulin availability to trigger the uptake or utilization of glucose. Unusually high concentration of serum lipids caused by increase in the transportation of free fatty acids from the peripheral fat depots due to inhibition of the sensitive lipase by insulin has been reported [26,27]. This prominent high lipid in the blood may therefore be taken as a result of the uninhibited actions of hormones involved in lipids catabolism on the fat depots caused probably by administration of the extract of the herb.…”

Section: Discussionmentioning

confidence: 99%

<i>Brillantasia patula</i> Aqueous Leaf Extract Averts Hyperglycermia, Lipid Peroxidation, and Alterations in Hematological Parameters in Alloxan-Induced Diabetic Rats

Anigboro¹,

Avwioroko²,

Tonukari³

2018

IJBSE

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The protective effects of aqueous leaf extract of Brillantasia patula against hyperglycermia, lipid peroxidation, and alterations in hematological parameters in diabetic Wistar rats were investigated. The study consisted of six treatment groups, with five animals each, designated as Group-1 (healthy), Group-2 (diabetic control) and Groups 3-6 (diabetic rats treated with 500, 1000, 1500, and 2000 mg/kgbwt of extract, respectively). Rats were administered their respective doses orally, and daily, for 14 days. Thereafter, the effects on serum glucose levels, liver and kidney functions, lipid peroxidation, free radical scavenger and hematological parameters were analyzed. Blood glucose levels reduced markedly in diabetic rats given the plant extract relative to diabetic control. Both serum creatinine and urea decreased significantly in treated diabetic rats at extract doses of 1000 mg/kgbwt and above. Reductions in serum cholesterol (p<0.05) and triglyceride levels (p<0.05) were also observed. Elevated total serum protein and globulin in diabetic control was decreased in all treated groups. Haematological indices of groups given the extract were noticeably enhanced. Similarly, kidney, heart and liver glutathione (GSH) levels increased significantly in groups treated compared to diabetic control; lipid peroxidation in kidney and heart also decreased significantly in all the treated groups. Liver catalase activity improved. Serum alanine and aspartate aminotransferases activities widely lowered in Groups 3 and 4. The study indicates that Brillantaisia patula aqueous leaf extract exhibits potential hypoglycemic effect, prevents lipid peroxidation, boosts haematological parameters, and could protect liver and renal damage associated with diabetes especially at doses of 500 -1000 mg/kgbwt.

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Isoalantolactone derivative promotes glucose utilization in skeletal muscle cells and increases energy expenditure in db/db mice via activating AMPK-dependent signaling

Cited by 19 publications

References 56 publications

Inhibitory evaluation ofCurculigo latifoliaon α-glucosidase, DPP (IV) andin vitrostudies in antidiabetic with molecular docking relevance to type 2 diabetes mellitus

Inhibitory evaluation ofCurculigo latifoliaon α-glucosidase, DPP (IV) andin vitrostudies in antidiabetic with molecular docking relevance to type 2 diabetes mellitus

Testosterone supplementation improves insulin responsiveness in HFD fed male T2DM mice and potentiates insulin signaling in the skeletal muscle and C2C12 myocyte cell line

<i>Brillantasia patula</i> Aqueous Leaf Extract Averts Hyperglycermia, Lipid Peroxidation, and Alterations in Hematological Parameters in Alloxan-Induced Diabetic Rats

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Isoalantolactone derivative promotes glucose utilization in skeletal muscle cells and increases energy expenditure in db/db mice via activating AMPK-dependent signaling

Cited by 19 publications

References 56 publications

Inhibitory evaluation ofCurculigo latifoliaon α-glucosidase, DPP (IV) andin vitrostudies in antidiabetic with molecular docking relevance to type 2 diabetes mellitus

Inhibitory evaluation ofCurculigo latifoliaon α-glucosidase, DPP (IV) andin vitrostudies in antidiabetic with molecular docking relevance to type 2 diabetes mellitus

Testosterone supplementation improves insulin responsiveness in HFD fed male T2DM mice and potentiates insulin signaling in the skeletal muscle and C2C12 myocyte cell line

&lt;i&gt;Brillantasia patula&lt;/i&gt; Aqueous Leaf Extract Averts Hyperglycermia, Lipid Peroxidation, and Alterations in Hematological Parameters in Alloxan-Induced Diabetic Rats

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<i>Brillantasia patula</i> Aqueous Leaf Extract Averts Hyperglycermia, Lipid Peroxidation, and Alterations in Hematological Parameters in Alloxan-Induced Diabetic Rats