title: The association between insulin and low-density lipoprotein receptors.
abstract: The insulin receptor (IR) and low-density lipoprotein receptor (LDLR) maintain glucose and lipid metabolism, respectively. Diabetes is associated with increased blood glucose, dyslipidaemia and increased risk of atherosclerosis. We hypothesise that interactions between IR and LDLR play a role in the atherosclerotic process in subjects with diabetes. Therefore, in this work we studied potential interactions between these two receptors. Our data show an intracellular and surface membrane-bound co-association of IR and LDLR. The co-association makes LDLR functionally poor in clearing extra-cellular LDL particles. A short 10 min exposure of cells to insulin disrupts the association between the two receptors and generates LDLR with higher LDL clearing activity without any change in protein expression. This co-association of LDLR with IR and their dissociation by insulin may be an important part of the regulatory mechanism of the normal physiological receptor function in a biological system. Modulation of receptor co-association is potentially a therapeutic target to reduce cardiovascular risk, and further studies are needed to investigate this possibility.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, India.
authors.forename: Gopalakrishnan
authors.initials: G
authors.lastname: Ramakrishnan
authors.forename: Albina
authors.initials: A
authors.lastname: Arjuman
authors.forename: Shilpa
authors.initials: S
authors.lastname: Suneja
authors.forename: Chandana
authors.initials: C
authors.lastname: Das
authors.forename: Nimai C
authors.initials: NC
authors.lastname: Chandra
mesh_terms: D050197:Atherosclerosis / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D007004:Hypoglycemic Agents; D007328:Insulin / Q000502:physiology*; D050356:Lipid Metabolism / Q000502:physiology; D008077:Lipoproteins, LDL / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism*; D012307:Risk Factors
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D011972:Receptor, Insulin