English Journal

GdCl3 reduces hyperglycaemia through Akt/FoxO1-induced suppression of hepatic gluconeogenesis in Type 2 diabetic mice.

Wang Q, Wang N, Dong M, Chen F, Li Z, Chen Y.Author information *Jiangsu Province Key Laboratory of Human Functional Genomics, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing 210029, China.AbstractGdCl3 (gadolinium chloride) has been shown to reduce blood glucose; however, the underlying mechanism remains unclear. Liver gluconeogenesis is an important pathway involved in the maintenance of glucose homoeostasis. The aim of the present study was to investigate the role of GdCl3 in hepatic gluconeogenesis and explore the precise molecular mechanism. Animals from a classical Type 2 diabetic mouse model, created by exposing C57BL/6J mice to a high-fat diet for 4 months, were treated with GdCl3 or saline. Body weight, blood glucose and insulin sensitivity were monitored. It was observed that GdCl3 significantly reduced blood glucose levels and improved insulin sensitivity. A pyruvate tolerance test showed further that GdCl3 suppressed gluconeogenesis in diabetic mice. In the livers of GdCl3-treated mice, the expression of Pepck (phosphoenolpyruvate carboxykinase) and G6pase (glucose-6-phosphatase), the key enzymes in gluconeogenesis, were dramatically reduced. Furthermore, experiments in hepatocarcinoma cells revealed that GdCl3 activated the Akt pathway to promote the phosphorylation of FoxO1 (forkhead box O1), leading to the suppression of gluconeogenesis by reducing the expression of PEPCK and G6Pase and resulting in decreased cellular production of glucose. Comparable results were observed in the livers of GdCl3-treated mice. In addition, we have shown that GdCl3 augmented the role of insulin to control hepatic glucose production. We conclude that GdCl3 reduces hyperglycaemia via the Akt/FoxO1-induced suppression of hepatic gluconeogenesis, both in Type 2 diabetic mice (in vivo) and in hepatocarcinoma cells (in vitro), suggesting that GdCl3 may be a potential therapeutic agent for diabetes.
Clinical science (London, England : 1979).Clin Sci (Lond).2014 Jul 1;127(2):91-100. doi: 10.1042/CS20130670.
GdCl3 (gadolinium chloride) has been shown to reduce blood glucose; however, the underlying mechanism remains unclear. Liver gluconeogenesis is an important pathway involved in the maintenance of glucose homoeostasis. The aim of the present study was to investigate the role of GdCl3 in hepatic gluco
PMID 24444370

Acute and long-term effects of arsenite in HepG2 cells: modulation of insulin signaling.

Hamann I1, Petroll K, Hou X, Anwar-Mohamed A, El-Kadi AO, Klotz LO.Author information 1Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada.AbstractEpidemiological studies have indicated a relationship between the prevalence of diabetes and exposure to arsenic. Mechanisms by which arsenic may cause this diabetogenic effect are largely unknown. The phosphoinositide 3'-kinase (PI3K)/Akt signaling pathway plays an important role in insulin signaling by controlling glucose metabolism, in part through regulating the activity of FoxO transcription factors. The present study aimed at investigating the effect of short and long-term exposure to arsenite on insulin signaling in HepG2 human hepatoma cells, the role of PI3K/Akt signaling therein and the modulation of target genes controlled by insulin. Exposure of cells to arsenite for 24 h rendered cells less responsive toward stimulation of Akt by insulin. At the same time, short-term exposure to arsenite induced a concentration-dependent increase in phosphorylation of Akt at Ser-473, followed by phosphorylation of FoxO proteins at sites known to be phosphorylated by Akt. Phosphorylation of FoxOs was prevented by wortmannin, pointing to the involvement of PI3K. Arsenite exposure resulted in attenuation of FoxO DNA binding and in nuclear exclusion of FoxO1a-EGFP. A 24-h exposure of HepG2 cells to submicromolar concentrations of arsenite resulted in downregulation of glucose 6-phosphatase (G6Pase) and selenoprotein P (SelP) mRNA levels. Curiously, arsenite had a dual effect on SelP protein levels, inducing a small increase in the nanomolar and a distinct decrease in the micromolar concentration range. Interestingly, arsenite-induced long-term effects on G6Pase and SelP mRNA or SelP protein levels were not blocked by the PI3K inhibitor, wortmannin. In conclusion, arsenite perturbs cellular signaling pathways involved in fuel metabolism: it impairs cellular responsiveness toward insulin, while at the same time stimulating insulin-like signaling to attenuate the expression of genes involved in glucose metabolism and the release of the hepatokine SelP, which is known to modulate peripheral insulin sensitivity.
Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine.Biometals.2014 Apr;27(2):317-32. doi: 10.1007/s10534-014-9714-y. Epub 2014 Feb 18.
Epidemiological studies have indicated a relationship between the prevalence of diabetes and exposure to arsenic. Mechanisms by which arsenic may cause this diabetogenic effect are largely unknown. The phosphoinositide 3'-kinase (PI3K)/Akt signaling pathway plays an important role in insulin signali
PMID 24535192

Polysaccharides from Liriopes Radix ameliorates hyperglycemia via various potential mechanisms in diabetic rats.

Xiao ZQ1, Wang YL, Gan SR, Chen JC.Author information 1Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji School of Pharmaceutical Sciences, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.AbstractBACKGROUND: Liriopes Radix, which is regarded as both drug and healthy diet, is drunk as tea and used in traditional Chinese medicine to treat diabetes. Based on our previous studies, investigated the hypoglycemic effects and explored the mechanisms of total polysaccharides from Liriope spicata var. prolifera (Liriopes Radix) in a diabetic rat model.
Journal of the science of food and agriculture.J Sci Food Agric.2014 Mar 30;94(5):975-82. doi: 10.1002/jsfa.6347. Epub 2013 Sep 10.
BACKGROUND: Liriopes Radix, which is regarded as both drug and healthy diet, is drunk as tea and used in traditional Chinese medicine to treat diabetes. Based on our previous studies, investigated the hypoglycemic effects and explored the mechanisms of total polysaccharides from Liriope spicata var.
PMID 23939938

Japanese Journal

Water Extracts of Immature Rubus coreanus Regulate Lipid Metabolism in Liver Cells

Bhandary Bidur,Lee Geum-Hwa,Marahatta Anu [他],Lee Hak-Yong,Kim Sun-Young,So Byung-Ok,Kwon Ji-Wung,Song Ji-Young,Lee Hee-Kwon,Kim Hyung-Ryong,Chae Soo-Wan,Chae Han-Jung
Biological and Pharmaceutical Bulletin 35(11), 1907-1913, 2012
… RCE treatment also showed an increase in phosphorylation of foxhead box protein 01 (FoXo-1) and 5-adenosine monophosphate-activated protein kinase (AMPK), thus lowering expression of phosphoenolpyruvate carboxykinase (PEPCK) and G6Pase, which might be a major pathway for cholesterol biosynthesis inhibition. …
NAID 130001872247

An Active Part of Artemisia sacrorum Ledeb. Suppresses Gluconeogenesis through AMPK Mediated GSK3β and CREB Phosphorylation in Human HepG2 Cells

Yuan Hai-Dan,Piao Guang-Chun
Bioscience, biotechnology, and biochemistry 75(6), 1079-1084, 2011-06-23
… PEASL downregulated the gluconeogenesis gene expression of peroxisome proliferation activated receptor-γ coactivator-1α (PGC-1α), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6Pase) in a concentration-dependent manner. …
NAID 10029327928

Anti-Diabetic Effects of Actinidia arguta Polyphenols on Rats and KK-A^y Mice

KURAKANE Shizue,YAMADA Noriko,SATO Hideyo,IGARASHI Kiharu
Food science and technology research 17(2), 93-102, 2011-03-01
… A decrease in the G6Pase activity and increase in the ACO or CPT activities in the liver of KK-Ay mice fed AP or isoquercitrin suggested that the suppression of glu-coneogenesis and the enhancement of β-oxidation of lipids, as well as the inhibition of maltase by AP and isoquercitrin, might also be related to their anti-diabetic effects. …
NAID 10028188956

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