Palbinone and triterpenes from Moutan Cortex (Paeonia suffruticosa, Paeoniaceae) stimulate glucose uptake and glycogen synthesis via activation of AMPK in insulin-resistant human HepG2 Cells

2009 ◽  
Vol 19 (19) ◽  
pp. 5556-5559 ◽  
Author(s):  
Do Thi Ha ◽  
Dao Trong Tuan ◽  
Nguyen Bich Thu ◽  
Nguyen Xuan Nhiem ◽  
Tran Minh Ngoc ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Hepg2 Cells ◽  
Glycogen Synthesis ◽  
Paeonia Suffruticosa ◽  
Insulin Resistant ◽  
Moutan Cortex

Selected compounds derived from Moutan Cortex stimulated glucose uptake and glycogen synthesis via AMPK activation in human HepG2 cells

2010 ◽  
Vol 131 (2) ◽  
pp. 417-424 ◽  
Author(s):  
Do Thi Ha ◽  
Trinh Nam Trung ◽  
Tran Thi Hien ◽  
Trong Tuan Dao ◽  
Namhui Yim ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Hepg2 Cells ◽  
Glycogen Synthesis ◽  
Ampk Activation ◽  
Moutan Cortex

Muscle glucose uptake during and after exercise is normal in insulin-resistant rats

1993 ◽  
Vol 264 (2) ◽  
pp. E167-E172 ◽  
Author(s):  
M. Kusunoki ◽  
L. H. Storlien ◽  
J. MacDessi ◽  
N. D. Oakes ◽  
C. Kennedy ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Glucose Transporter ◽  
Treadmill Exercise ◽  
Glycogen Synthesis ◽  
Insulin Stimulation ◽  
Adult Rats ◽  
Insulin Resistant ◽  
Glucose Levels ◽  
Hindlimb Muscles ◽  
Postexercise Recovery

It is not generally known whether impaired stimulation of muscle glucose metabolism in insulin-resistant states is specific to insulin stimulation. Our aim was to examine whether glucose uptake responded normally to exercise and postexercise recovery in insulin-resistant high-fat-fed (HFF) rats. Three-week HFF or Chow-fed [control (Con)] adult rats were studied 5 days after cannulation. Before, during, or immediately after (recovery) 50 min of treadmill exercise, bolus 2-deoxy-[3H]glucose and [14C]glucose were administered to estimate muscle glucose uptake (R'g) and glycogen incorporation rates. Mean exercise and recovery plasma glucose levels were similar in HFF and Con rats. In hindlimb muscles sampled, exercise and recovery R'g were similar in HFF and Con (e.g., red quadriceps exercise 104 +/- 13 vs. 113 +/- 8, recovery 45.3 +/- 3.9 vs. 47.7 +/- 4.5 mumol.100 g-1.min-1, respectively). Moreover, muscle glucose transporter (GLUT-4) content was not reduced in HFF rats. Glycogen resynthesis accounted almost entirely for R'g during recovery and was equivalent between groups. We conclude that impaired muscle glucose uptake and glycogen synthesis in HFF rats are characteristic of insulin but not of exercise or postexercise stimulation.

scholarly journals Anti-Diabetic Activity of 2,3,6-Tribromo-4,5-Dihydroxybenzyl Derivatives from Symphyocladia latiuscula through PTP1B Downregulation and α-Glucosidase Inhibition

Marine Drugs ◽  
2019 ◽  
Vol 17 (3) ◽  
pp. 166 ◽  
Author(s):  
Pradeep Paudel ◽  
Su Seong ◽  
Hye Park ◽  
Hyun Jung ◽  
Jae Choi
Keyword(s):  
Glucose Uptake ◽  
Methyl Ether ◽  
In Silico ◽  
Hepg2 Cells ◽  
Halogen Bond ◽  
Biological Activities ◽  
Tyrosine Phosphatase ◽  
Docking Simulations ◽  
Insulin Resistant ◽  
Ring Number

The marine alga, Symphyocladia latiuscula (Harvey) Yamada, is a good source of bromophenols with numerous biological activities. This study aims to characterize the anti-diabetic potential of 2,3,6-tribromo-4,5-dihydroxybenzyl derivatives isolated from S. latiuscula via their inhibition of tyrosine phosphatase 1B (PTP1B) and α-glucosidase. Additionally, this study uses in silico modeling and glucose uptake potential analysis in insulin-resistant (IR) HepG2 cells to reveal the mechanism of anti-diabetic activity. This bioassay-guided isolation led to the discovery of three potent bromophenols that act against PTP1B and α-glucosidase: 2,3,6-tribromo-4,5-dihydroxybenzyl alcohol (1), 2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether (2), and bis-(2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether) (3). All compounds inhibited the target enzymes by 50% at concentrations below 10 μM. The activity of 1 and 2 was comparable to ursolic acid (IC50; 8.66 ± 0.82 μM); however, 3 was more potent (IC50; 5.29 ± 0.08 μM) against PTP1B. Interestingly, the activity of 1–3 against α-glucosidase was 30–110 times higher than acarbose (IC50; 212.66 ± 0.35 μM). Again, 3 was the most potent α-glucosidase inhibitor (IC50; 1.92 ± 0.02 μM). Similarly, 1–3 showed concentration-dependent glucose uptake in insulin-resistant HepG2 cells and downregulated PTP1B expression. Enzyme kinetics revealed different modes of inhibition. In silico molecular docking simulations demonstrated the importance of the 7–OH group for H-bond formation and bromine/phenyl ring number for halogen-bond interactions. These results suggest that bromophenols from S. latiuscula, especially highly brominated 3, are inhibitors of PTP1B and α-glucosidase, enhance insulin sensitivity and glucose uptake, and may represent a novel class of anti-diabetic drugs.

scholarly journals Exposure to Perfluoro-Octanoic Acid Associated With Upstream Uncoupling of the Insulin Signaling in Human Hepatocyte Cell Line

2021 ◽  
Vol 12 ◽  
Author(s):  
Luca De Toni ◽  
Andrea Di Nisio ◽  
Maria Santa Rocca ◽  
Diego Guidolin ◽  
Alice Della Marina ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Hepg2 Cells ◽  
Octanoic Acid ◽  
Periodic Acid ◽  
Glycogen Synthesis ◽  
Human Hepatocyte ◽  
Pathogenic Mechanism ◽  
Low Grade ◽  
Glut 4 ◽  
Long Term Treatment

Perfluoro–alkyl substances (PFAS) are chemical pollutants with prevalent stability and environmental persistence. Exposure to PFAS, particularly perfluoro-octanoic acid (PFOA), has been associated with increased diabetes-related cardiovascular mortality in subjects residing areas of high environmental contamination, however the exact pathogenic mechanism remains elusive. Here we used HepG2 cells, an in vitro model of human hepatocyte, to investigate the possible role of PFOA exposure in the alteration of hepatic glucose metabolism. HepG2 cells were exposed for 24 hours to PFOA at increasing concentration from 0 to 1000 ng/mL and then stimulated with 100 nm Insulin (Ins). The consequent effect on glycogen synthesis, glucose uptake and Glut-4 glucose transporter translocation was then evaluated by, respectively, Periodic Acid Schiff (PAS) staining, 2-deoxyglucose (2-DG) uptake assay and immunofluorescence. Exposure to PFOA was associated with reduced glycogen synthesis and glucose uptake, at concentration equal or greater than, respectively, 0,1 ng/mL and 10 ng/mL, with parallel impaired membrane translocation of Glut-4 upon Ins stimulation. Western blot analysis showed early uncoupling of Insulin Receptor (InsR) activation from the downstream Akt and GSK3 phosphorylation. Computational docking analysis disclosed the possible stabilizing effect of PFOA on the complex between InsR and GM3 ganglioside, previously shown to be associated with the low grade chronic inflammation-related insulin resistance. Consistently, long term treatment with glucosyl-ceramide synthase inhibitor PDMP was able to largely restore glycogen synthesis, glucose uptake and Glut-4 translocation upon Ins stimulation in HepG2 exposed to PFOA. Our data support a novel pathogenic mechanism linking exposure to PFOA to derangement of hepatocyte cell metabolism.

Skeletal muscle glucose metabolism in obesity-prone and obesity-resistant rats

1993 ◽  
Vol 264 (6) ◽  
pp. R1224-R1228 ◽  
Author(s):  
M. J. Pagliassotti ◽  
K. A. Shahrokhi ◽  
J. O. Hill
Keyword(s):  
Skeletal Muscle ◽  
Body Weight ◽  
Weight Gain ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Glycogen Synthase ◽  
Body Weight Gain ◽  
Glycogen Synthesis ◽  
Insulin Resistant ◽  
Wide Range

Ad libitum access to a high-fat (HF) diet produces a wide range of weight gain in rats. Rats most susceptible to weight gain on such a diet (obesity prone; OP) are more insulin resistant after 4-5 wk of diet exposure than are those most resistant (obesity resistant; OR) to weight gain. To investigate whether skeletal muscle glucose metabolism contributes to insulin resistance in this model, insulin-stimulated glucose metabolism was assessed in the perfused hindquarter of rats exposed to either a low-fat (LF, n = 6) or HF diet for 5 wk. Delineation of OP (n = 6) and OR (n = 6) rats was based on body weight gain. OP rats gained 60% more body weight while eating only 10% more energy than OR rats. Single-pass perfusions were carried out for 2 h in the presence of glucose, insulin, and [U-14C]glucose. Insulin-stimulated glucose uptake (mumol.100 g-1.min-1) was 14.2 +/- 0.9 in LF, 11.1 +/- 0.8 in OR, and 6.2 +/- 0.6 in OP. Glucose oxidation (mumol.100 g-1.min-1) was 1.7 +/- 0.3 and 1.2 +/- 0.3 in LF and OR, respectively, but was 0.2 +/- 0.1 in OP. Net glycogen synthesis was significantly reduced in OP compared with OR and LF despite similar glycogen synthase I activity. Muscle triglyceride concentration was not significantly different in OR and OP rats. These results demonstrate significant defects in skeletal muscle glucose uptake and disposal in rats most susceptible to HF diet-induced obesity. Clearly, the heterogeneous response to a HF diet involves not only body weight gain but also skeletal muscle fuel metabolism.

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