title: Glucose and fatty acid metabolism in a 3 tissue in-vitro model challenged with normo- and hyperglycaemia.
abstract: Nutrient balance in the human body is maintained through systemic signaling between different cells and tissues. Breaking down this circuitry to its most basic elements and reconstructing the metabolic network in-vitro provides a systematic method to gain a better understanding of how cross-talk between the organs contributes to the whole body metabolic profile and of the specific role of each different cell type. To this end, a 3-way connected culture of hepatocytes, adipose tissue and endothelial cells representing a simplified model of energetic substrate metabolism in the visceral region was developed. The 3-way culture was shown to maintain glucose and fatty acid homeostasis in-vitro. Subsequently it was challenged with insulin and high glucose concentrations to simulate hyperglycaemia. The aim was to study the capacity of the 3-way culture to maintain or restore normal circulating glucose concentrations in response to insulin and to investigate the effects these conditions on other metabolites involved in glucose and lipid metabolism. The results show that the system's metabolic profile changes dramatically in the presence of high concentrations of glucose, and that these changes are modulated by the presence of insulin. Furthermore, we observed an increase in E-selectin levels in hyperglycaemic conditions and increased IL-6 concentrations in insulin-free-hyperglycaemic conditions, indicating, respectively, endothelial injury and proinflammatory stress in the challenged 3-way system.
authors.affiliation: Division of Metabolic Diseases, Department of Clinical and Experimental Medicine, University of Padua, Padua, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Iori
authors.forename: Bruna
authors.initials: B
authors.lastname: Vinci
authors.forename: Ellen
authors.initials: E
authors.lastname: Murphy
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Marescotti
authors.forename: Angelo
authors.initials: A
authors.lastname: Avogaro
authors.forename: Arti
authors.initials: A
authors.lastname: Ahluwalia
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D019040:E-Selectin / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D022781:Hepatocytes / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D046509:Tissue Culture Techniques
chemical_list: D019040:E-Selectin; D005227:Fatty Acids; D007328:Insulin; D015850:Interleukin-6; D019344:Lactic Acid; D005947:Glucose