title: Impact of keratin intermediate filaments on insulin-mediated glucose metabolism regulation in the liver and disease association.
abstract: In all cells, a tight regulation exists between glucose uptake and utilization to prevent diseases related to its perturbed metabolism. In insulin-targeted cells, such as hepatocytes, proper glucose utilization requires an elaborate interplay between the insulin receptor, the glucose transporter, and mitochondria that involves the participation of actin microfilaments and microtubules. In addition, there is increasing evidence of an involvement of the third cytoskeletal network provided by intermediate filaments (IFs). Keratins belong to the multigene family of IF proteins, coordinately expressed as distinct pairs within the context of epithelial cell differentiation. Hepatocyte IFs are made up of the [keratin (K)8/K18] pair only, whereas pancreatic β-cell IFs additionally include small amounts of K7. There are accumulating examples of K8/K18 involvement in the glucose-insulin cross-talk, including the modulation of plasma glucose levels, insulin release from pancreatic β-cells, and insulin-mediated glucose uptake and glycogen production in hepatocytes after a K8/K18 loss. This review integrates the mechanistic features that support such an impact of K8/K18 IFs on insulin-dependent glucose metabolism regulation in liver and its implication in glucose- or insulin-associated diseases.
authors.affiliation: Centre de Recherche sur le Cancer, Université Laval, and Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec City, Québec, Canada.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Roux
authors.affiliation: Centre de Recherche sur le Cancer, Université Laval, and Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec City, Québec, Canada.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Gilbert
authors.affiliation: Centre de Recherche sur le Cancer, Université Laval, and Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec City, Québec, Canada.
authors.forename: Anne
authors.initials: A
authors.lastname: Loranger
authors.affiliation: Centre de Recherche sur le Cancer, Université Laval, and Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec City, Québec, Canada normand.marceau@crchudequebec.ulaval.ca.
authors.forename: Normand
authors.initials: N
authors.lastname: Marceau
mesh_terms: D000818:Animals; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D007382:Intermediate Filaments / Q000502:physiology*; D007633:Keratins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*
chemical_list: D007328:Insulin; D007633:Keratins; D005947:Glucose
keywords: cell signaling; cytoskeleton; hepatocyte; hormone receptor; protein kinases