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Gsk3 AND Akt AND Glucose

Nelly T Fabre, Karina Thieme, Karolline S Silva, Sérgio Catanozi, Ana Mercedes Cavaleiro, Danilo A C Pinto, Maristela M Okamoto, Mychel Raony P T Morais, Bárbara Falquetto, Telma M Zorn, Ubiratan F Machado, Marisa Passarelli, Maria Lúcia Correa-Giannella
Because of the paucity of information regarding metabolic effects of advanced glycation end products (AGEs) on liver, we evaluated effects of AGEs chronic administration in (1) insulin sensitivity; (2) hepatic expression of genes involved in AGEs, glucose and fat metabolism, oxidative stress and inflammation and; (3) hepatic morphology and glycogen content. Rats received intraperitoneally albumin modified (AlbAGE) or not by advanced glycation for 12 weeks. AlbAGE induced whole-body insulin resistance concomitantly with increased hepatic insulin sensitivity, evidenced by activation of AKT, inactivation of GSK3, increased hepatic glycogen content, and decreased expression of gluconeogenesis genes...
February 24, 2017: Molecular and Cellular Endocrinology
Dan Tang, Qi-Bin Chen, Xue-Lei Xin, Haji-Akber Aisa
Diabetes is a metabolic disease with the characteristic of high blood glucose (hyperglycemia). In our previous study, we found that nigelladines A-C (compounds A-C), three norditerpenoid alkaloids from the seeds of Nigella glandulifera Freyn (Ranunculaceae) exhibited protein of tyrosine phosphatase 1B (PTP1B) inhibitory activity in vitro. In the present study, we further investigated their anti-diabetes activities in L6 moytubes and illuminated the mechanisms of action of compounds A-C. Several parameters of glucose metabolism such as glucose consumption, glycogen content and hexokinase activity were increased by compounds A-C...
March 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Fujie Yan, Guanhai Dai, Xiaodong Zheng
This study evaluated the capacity of mulberry anthocyanin extract (MAE) on insulin resistance amelioration in HepG2 cells induced by high glucose and palmitic acid and diabetes-related metabolic changes in type 2 diabetic mice. In vitro, MAE alleviated insulin resistance in HepG2 cells and increased glucose consumption, glucose uptake and glycogen content. Enzyme activities of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) were decreased due to PPARγ coactivator 1α (PGC-1α) and forkhead box protein O1 (FOXO1) inhibition...
October 2016: Journal of Nutritional Biochemistry
Jia-Jia Song, Qian Wang, Min Du, Tian-Ge Li, Bin Chen, Xue-Ying Mao
SCOPE: Recently, casein glycomacropeptide (GMP)-derived peptide was found to possess potent antioxidant and anti-inflammatory activities. In this study, the improvement effects and underlying molecular mechanisms of GMP-derived peptide on hepatic insulin resistance were investigated. METHODS AND RESULTS: The peptide IPPKKNQDKTE was identified from GMP papain hydrolysates by LC-ESI-MS/MS. Effects of IPPKKNQDKTE on glucose metabolism and expression levels of the hepatic insulin signaling proteins in high glucose-induced insulin-resistant HepG2 cells were evaluated...
August 9, 2016: Molecular Nutrition & Food Research
Yuehui Zhang, Xue Sun, Xiaoyan Sun, Fanci Meng, Min Hu, Xin Li, Wei Li, Xiao-Ke Wu, Mats Brännström, Ruijin Shao, Håkan Billig
Peripheral insulin resistance and hyperandrogenism are the primary features of polycystic ovary syndrome (PCOS). However, how insulin resistance and hyperandrogenism affect uterine function and contribute to the pathogenesis of PCOS are open questions. We treated rats with insulin alone or in combination with human chorionic gonadotropin (hCG) and showed that peripheral insulin resistance and hyperandrogenism alter uterine morphology, cell phenotype, and cell function, especially in glandular epithelial cells...
2016: Scientific Reports
Yuntang Wu, Huizi Lu, Huijun Yang, Chunlei Li, Qian Sang, Xinyan Liu, Yongzhe Liu, Yongming Wang, Zhong Sun
The present study was performed to evaluate the insulin-like effects of zinc in normal L6 myotubes as well as its ability to alleviate insulin resistance. Glucose consumption was measured in both normal and insulin-resistant L6 myotubes. Western blotting and immunofluorescence revealed that zinc exhibited insulin-like glucose transporting effects by activating key markers that are involved in the insulin signaling cascade (including Akt, GLUT4 and GSK3β), and downregulating members of the insulin signaling feedback cascade such as mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase (S6K1)...
August 2016: Journal of Nutritional Biochemistry
Peter E M Gibbs, Tihomir Miralem, Nicole Lerner-Marmarosh, Mahin D Maines
Insulin's stimulation of glucose uptake by binding to the IRK extracellular domain is compromised in diabetes. We have recently described an unprecedented approach to stimulating glucose uptake. KYCCSRK (P2) peptide, corresponding to the C-terminal segment of hBVR, was effective in binding to and inducing conformational change in the IRK intracellular kinase domain. Although myristoylated P2, made of L-amino acids, was effective in cell culture, its use for animal studies was unsuitable. We developed a peptidase-resistant formulation of the peptide that was efficient in both mice and cell culture systems...
2016: Journal of Diabetes Research
Tihomir Miralem, Nicole Lerner-Marmarosh, Peter E M Gibbs, Jermaine L Jenkins, Chelsea Heimiller, Mahin D Maines
Biliverdin reductase A (BVR) and Akt isozymes have overlapping pleiotropic functions in the insulin/PI3K/MAPK pathway. Human BVR (hBVR) also reduces the hemeoxygenase activity product biliverdin to bilirubin and is directly activated by insulin receptor kinase (IRK). Akt isoenzymes (Akt1-3) are downstream of IRK and are activated by phosphatidylinositol-dependent kinase 1 (PDK1) phosphorylating T(308) before S(473) autophosphorylation. Akt (RxRxxSF) and PDK1 (RFxFPxFS) binding motifs are present in hBVR. Phosphorylation of glycogen synthase kinase 3 (GSK3) isoforms α/β by Akts inhibits their activity; nonphosphorylated GSK3β inhibits activation of various genes...
August 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Celine Latouche, Alaina Natoli, Medini Reddy-Luthmoodoo, Sarah E Heywood, James A Armitage, Bronwyn A Kingwell
BACKGROUND: The regulation of microRNAs (miRNAs) at different stages of the progression of type 2 diabetes mellitus (T2DM) and their role in glucose homeostasis was investigated. METHODS: Microarrays were used to assess miRNA expression in skeletal muscle biopsies taken from healthy individuals and patients with pre-diabetes or T2DM, and insulin resistant offspring of rat dams fed a high fat diet during pregnancy. RESULTS: Twenty-three miRNAs were differentially expressed in patients with T2DM, and 7 in the insulin resistant rat offspring compared to their controls...
2016: PloS One
Hong Chen, Abul Fajol, Miriam Hoene, Bingbing Zhang, Erwin D Schleicher, Yun Lin, Carsten Calaminus, Bernd J Pichler, Cora Weigert, Hans U Häring, Florian Lang, Michael Föller
Metabolic syndrome is characterized by insulin resistance, obesity, and dyslipidemia. It is the consequence of an imbalance between caloric intake and energy consumption. Adiponectin protects against metabolic syndrome. Insulin-induced signaling includes activation of PI3 kinase and protein kinase B (PKB)/Akt. PKB/Akt in turn inactivates glycogen synthase kinase (GSK) 3, a major regulator of metabolism. Here, we studied the significance of PI3K-dependent GSK3 inactivation for adiponectin formation in diet-induced metabolic syndrome...
May 17, 2016: Proceedings of the National Academy of Sciences of the United States of America
Rosa Gómez-Villafuertes, Paula García-Huerta, Juan Ignacio Díaz-Hernández, M Teresa Miras-Portugal
The expression of purinergic P2X7 receptor (P2X7R) in neuroblastoma cells is associated to accelerated growth rate, angiogenesis, metastasis and poor prognosis. Noticeably, P2X7R allows the survival of neuroblastoma cells under restrictive conditions, including serum and glucose deprivation. Previously we identified specificity protein 1 (Sp1) as the main factor involved in the transcriptional regulation of P2rx7 gene, reporting that serum withdrawal triggers the expression of P2X7R in Neuro-2a (N2a) neuroblastoma cell line...
December 21, 2015: Scientific Reports
Tong-Yan Liu, Chang-Xiang Shi, Run Gao, Hai-Jian Sun, Xiao-Qing Xiong, Lei Ding, Qi Chen, Yue-Hua Li, Jue-Jin Wang, Yu-Ming Kang, Guo-Qing Zhu
Increased glucose production and reduced hepatic glycogen storage contribute to metabolic abnormalities in diabetes. Irisin, a newly identified myokine, induces the browning of white adipose tissue, but its effects on gluconeogenesis and glycogenesis are unknown. In the present study, we investigated the effects and underlying mechanisms of irisin on gluconeogenesis and glycogenesis in hepatocytes with insulin resistance, and its therapeutic role in type 2 diabetic mice. Insulin resistance was induced by glucosamine (GlcN) or palmitate in human hepatocellular carcinoma (HepG2) cells and mouse primary hepatocytes...
November 2015: Clinical Science (1979-)
M R King, N J Anderson, C Liu, E Law, M Cundiff, T M Mixcoatl-Zecuatl, C G Jolivalt
Peripheral neuropathy is a major complication associated with diabetes and central neuropathy characterized by Alzheimer's disease-like features in the brain is associated with increased dementia risk for patients with diabetes. Although glucose uptake into the cells of the nervous system is insulin-independent, contribution of impaired insulin support is clearly recognized to play a role, however not yet fully understood, in the development of neuropathy. In this study, we assessed the direct role of insulin on the peripheral nervous system (PNS) and central nervous system (CNS) of insulin-dependent type 1 diabetic rats...
September 10, 2015: Neuroscience
Maria Jose Perez-Alvarez, Laura Mateos, Alvaro Alonso, Francisco Wandosell
Epidemiological studies have suggested a differential response, males versus female, in stroke incidence and prognosis. These divergences in brain response after damage are based mostly on hormonal differences. To date, estradiol and progesterone administered independently have demonstrated neuroprotection after ischemia in animal models. Nonetheless, contradictory results were revealed using a combined administration. In order to evaluate the effects of combinatorial treatment administered after ischemia induction, we used two different approaches: in vivo and in vitro models...
December 2015: Molecular Neurobiology
Ernesto Bernal-Mizrachi, Rohit N Kulkarni, Donald K Scott, Franck Mauvais-Jarvis, Andrew F Stewart, Adolfo Garcia-Ocaña
Enhancing β-cell proliferation is a major goal for type 1 and type 2 diabetes research. Unraveling the network of β-cell intracellular signaling pathways that promote β-cell replication can provide the tools to address this important task. In a previous Perspectives in Diabetes article, we discussed what was known regarding several important intracellular signaling pathways in rodent β-cells, including the insulin receptor substrate/phosphatidylinositol-3 kinase/Akt (IRS-PI3K-Akt) pathways, glycogen synthase kinase-3 (GSK3) and mammalian target of rapamycin (mTOR) S6 kinase pathways, protein kinase Cζ (PKCζ) pathways, and their downstream cell-cycle molecular targets, and contrasted that ample knowledge to the small amount of complementary data on human β-cell intracellular signaling pathways...
March 2014: Diabetes
M Kubota, Y Sato, O Khookhor, K Ekberg, A V Chibalin, J Wahren
BACKGROUND: This study was undertaken to examine if C-peptide (C) may interact with hexameric insulin and facilitate its disaggregation into the physiologically active monomeric form. METHODS: Regular insulin (I) or an insulin analogue (IA) were injected s.c. in rats together with C or its C-terminal pentapeptide (PP). I or IA and C or PP were administered either as a physical mixture or into two separate s.c. depots. Whole body glucose utilization was evaluated using the euglycemic clamp technique...
February 2014: Diabetes/metabolism Research and Reviews
Min Wan, Karla F Leavens, Roger W Hunter, Shlomit Koren, Alexander von Wilamowitz-Moellendorff, Mingjian Lu, Santhosh Satapati, Qingwei Chu, Kei Sakamoto, Shawn C Burgess, Morris J Birnbaum
Insulin rapidly suppresses hepatic glucose production and slowly decreases expression of genes encoding gluconeogenic proteins. In this study, we show that an immediate effect of insulin is to redirect newly synthesized glucose-6-phosphate to glycogen without changing the rate of gluconeogenesis. This process requires hepatic Akt2, as revealed by blunted insulin-mediated suppression of glycogenolysis in the perfused mouse liver, elevated hepatic glucose production during a euglycemic-hyperinsulinemic clamp, or diminished glycogen accumulation during clamp or refeeding in mice without hepatic Akt2...
July 2, 2013: Cell Metabolism
Adriana C Lambertucci, Rafael H Lambertucci, Sandro M Hirabara, Rui Curi, Anselmo S Moriscot, Tatiana C Alba-Loureiro, Lucas Guimarães-Ferreira, Adriana C Levada-Pires, Diogo A A Vasconcelos, Donald F Sellitti, Tania C Pithon-Curi
In this study, we investigated the effect of glutamine (Gln) supplementation on the signaling pathways regulating protein synthesis and protein degradation in the skeletal muscle of rats with streptozotocin (STZ)-induced diabetes. The expression levels of key regulatory proteins in the synthetic pathways (Akt, mTOR, GSK3 and 4E-BP1) and the degradation pathways (MuRF-1 and MAFbx) were determined using real-time PCR and Western blotting in four groups of male Wistar rats; 1) control, non-supplemented with glutamine; 2) control, supplemented with glutamine; 3) diabetic, non-supplemented with glutamine; and 4) diabetic, supplemented with glutamine...
2012: PloS One
Chu-Wan Lee, Yao-Hsiang Shih, Shih-Ying Wu, Tingting Yang, Chingju Lin, Yu-Min Kuo
Cerebral hypoglycemia/hypometabolism is associated with Alzheimer's disease (AD) and is routinely used to assist clinical diagnosis of AD by brain imaging. However, whether cerebral hypoglycemia/hypometabolism contributes to the development of AD or is a response of reduced neuronal activity remains unclear. To investigate the causal relationship, we cultured the differentiated N2a neuroblastoma cells in glucose/pyruvate-deficient media (GDM). Shortly after the N2a cells cultured in the GDM, the mitochondria membrane potential was reduced and the AMP-activated-proteinkinase (AMPK), an energy sensor, was activated...
March 2013: Current Alzheimer Research
Laura Nocito, Delia Zafra, Joaquim Calbó, Jorge Domínguez, Joan J Guinovart
AIMS: Oral administration of sodium tungstate has shown hyperglycemia-reducing activity in several animal models of diabetes. We present new insights into the mechanism of action of tungstate. METHODS: We studied protein expression and phosphorylation in the liver of STZ rats, a type I diabetes model, treated with sodium tungstate in the drinking water (2 mg/ml) and in primary cultured-hepatocytes, through Western blot and Real Time PCR analysis. RESULTS: Tungstate treatment reduces the expression of gluconeogenic enzymes (PEPCK, G6Pase, and FBPase) and also regulates transcription factors accountable for the control of hepatic metabolism (c-jun, c-fos and PGC1α)...
2012: PloS One
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