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Children's Health Research Institute, London, Ontario, Canada
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Children's Health Research Institute, London, Ontario, Canada
Department of Pediatrics, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada
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. 2021 ). However, the mechanisms by which glucose deprivation alters IGFBP-1 phosphorylation is currently unknown. We hypothesized that AMPK (5′adenosine monophosphate-activated protein kinase), a key energy sensor, is activated by glucose deprivation
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pancreatic cells ( Johnston 1999 ). D-glucose deprivation can also induce the expression of genes such as heme oxygenase-1 ( Chang et al. 2002 ) and interleukin 6 ( Choi et al. 2013 ). Furthermore, in D-glucose-deprived cells, AMP-activated protein kinase
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The cellular mechanisms that lead to neuronal death following glucose deprivation are not known, although it is recognized that hypoglycemia can lead to perturbations in intracellular calcium ([Ca2+]i) levels. Recently, activation of A1 adenosine receptors (A1AR) has been shown to alter [Ca2+]i and promote neuronal death. Thus, we examined if A1AR activation contributes to hypoglycemia-induced neuronal injury using rat cortical neurons. First, we observed that hypoglycemia was associated with large increases in neuronal adenosine release. Next, decreased neuronal viability was seen with progressive reduction in glucose concentration (25, 6, 3, 0.75 and 0 mM). Using the calcium-sensitive dye, Fluo-3, we observed both acute and long-term changes in relative [Ca2+]i during hypoglycemic conditions. Demonstrating a role for adenosine in this process, both the loss in neuronal viability and the early changes in [Ca2+]i were reversed by treatment with A1AR antagonists (8-cyclopentyl, 1,3-dipropylxanthine; 9-chloro-2-(2-furyl)(1,2,4)-triazolo(1,5-c)quinazolin-5-amine; and N-cyclopentyl-9-methyladenine). We also found that hypoglycemia induced the expression of the pro-apoptotic enzyme, caspase-3, and that A1AR antagonism reversed hypoglycemia-induced caspase-3 activity. Collectively, these data show that hypoglycemia induces A1ARs activation leading to alterations in [Ca2+]i, which plays a prominent role in leading to hypoglycemia-induced neuronal death.
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. 2002 ). We have reported that AG blocks oxygen–glucose deprivation-induced apoptosis by preventing mitochondrial depolarization (loss of ΔΨ M ) ( Chung et al. 2007 ). Therefore, we examined the effect of ghrelin gene products on ΔΨ M using JC-1
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%) and l -glutamine (1%). All culture reagents were purchased from Sigma–Aldrich. For studies on glucose deprivation, the cells were incubated in a glucose-free medium (R1383 and D5030, Sigma–Aldrich). For the experiments, growing cells were plated on
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Department of Endocrinology, Central Laboratory, Department of Endocrinology and Metabolism, Department of Dentistry, Department of Education and Research, Provincial Hospital affiliated to Shandong University, Jinan, China
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riboside (AICA riboside), and nutrient deprivation including glucose and glutamine deficiency ( Lefebvre et al . 2001 , Lefebvre & Rosen 2005 ). For instance, glucose deprivation increases SNARK activity threefold in BHK fibroblasts ( Lefebvre et al
The Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
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The Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
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tumor therapeutic response ( Lin et al. 2017 , Cho et al. 2018 ). Cancer cells, compared to normal cells, are generally more susceptible to the cytotoxic effects of glucose deprivation, effects that are mediated, in part, by their increased
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complicated by fetal growth restriction ( Roos et al . 2007 , Zhang et al . 2017 ). mTOR regulation is multifactorial, illustrating the complexity of regulatory inputs this pathway coordinates. In growth restriction models, glucose deprivation downregulates
Department of Experimental Medicine, Montreal, Quebec, Canada
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Department of Experimental Medicine, Montreal, Quebec, Canada
Gerald Bronfman Department of Oncology, Montreal, Quebec, Canada
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Department of Experimental Medicine, Montreal, Quebec, Canada
Gerald Bronfman Department of Oncology, Montreal, Quebec, Canada
Biochemistry Department, McGill University, Montreal, Quebec, Canada
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Gerald Bronfman Department of Oncology, Montreal, Quebec, Canada
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of MTORC1 signaling ( Inoki et al . 2006 ). AMPK can also be activated by glucose deprivation through an AMP/ATP-independent mechanism ( Fig. 1 ), which is triggered by a glucose deprivation-induced decrease in fructose-1,6-bisphosphate levels
Centro de Investigaciones Endocrinológicas (CEDIE), Hospital de Niños Ricardo Gutiérrez, Gallo 1330, 1425 Buenos Aires, Argentina Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155 5th floor, 1121 Buenos Aires, Argentina
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. Yun H Lee M Kim SS Ha J 2005 Glucose deprivation increases mRNA stability of vascular endothelial growth factor through activation of AMP-activated protein kinase in DU145 prostate carcinoma . Journal of Biological Chemistry 280 9963 – 9972 .
