GLUT4 Associated Proteins as Therapeutic Targets for Diabetes

Broden      J. Morgan; Siew      Yeen Chai; Anthony      L. Albiston

Abstract

Type 2 diabetes is a complex, multifactorial disease resulting from insulin resistance in target tissues and the impairment of insulin secretion from the pancreas. One of the key metabolic actions of insulin is to control blood sugar levels by promoting glucose uptake into adipocyte and muscle cells. This is achieved by activation of a complex signal transduction cascade that stimulates the trafficking of the insulin responsive glucose transporter protein, GLUT4, from specific intracellular sites to the plasma membrane. This review is divided into two major sections. The first section gives an overview of GLUT4 trafficking and the second section focuses on the patents that have been acquired for GLUT4 associated proteins and which demonstrate potential as therapeutic targets for the treatment of diabetes. Inventions in this area include methods and agents to translocate GLUT4 to the plasma membrane independent of insulin and methods to increase the level of GLUT4 in insulin responsive cells.

Keywords: GLUT4, IRAP, NIDDM, insulin, AS160, FHOS, PI3K, myostatin, Diabetes, Glucose Homeostasis, carbohydrate, hyperglycaemic state, Comorbidities, blood pressure, obesity, blindness, renal failure, myocardial infarct, stroke, autonomic neuropathy, sulfonylureas, peptide hormone, glycogen/fatty acid synthesis, NMR spectroscopy, translocation, intrinsic tyrosine kinase, phosphorylation of IR substrates, phosphorylates, Src homology 2, nucleotide, skeletal, cardiac, muscle, endocytosis, tubulo-vesicular, cytoplasm, aminopeptidase, immunocytochemistry, vesicle,, biotinylation, Cytoplasmic Tail, Protein Interactions, adipocytes, phosphorylation, mammalian cell, fluorescence, mammalian cells, Nucleic acids, Microinjection, endogenous IRAP, Coenzyme, hyperglycaemia, hypertrophy, homeostasis, Transcriptional Regulation, myostatin gene, peroxisome proliferator, cholesterol, glucose metabolism, glucose tolerance, carcinogenic effect, Fatty Acids, Lupinoside, palmitate, ketoacidosis