title: Scaling it down: new in vitro tools to get the balance right.
abstract: Treatments for diabetes and obesity based on enteroendocrine hormones are a focus of research interest, partly due to the successes of glucagon-like peptide-1 (GLP-1) mimetic peptides in the treatment of diabetes and the correlation of altered enteroendocrine profiles with the positive metabolic outcomes of gastric bypass surgery. It is thought that simultaneous stimulation of more than one receptor might mimic the superior efficacy of the latter and dual or triple-agonist peptides are under investigation. An important step in developing multiple agonists is to establish the relative pharmacological potency and efficacy of new molecules at its different target receptors, and to optimise the balance of activities to achieve the desired treatment outcome. In a recent issue of the Biochemical Journal, Naylor et al. described how they used CRISPR technology to modulate endogenous receptor density in insulinoma cells to get the balance right for a dual incretin peptide engaging both GLP-1- and glucose-dependent insulinotropic polypeptide-receptors.
authors.affiliation: Metabolic Research Laboratories, Wellcome Trust/MRC Institute of Metabolic Science & MRC Metabolic Diseases Unit, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge CB2 0QQ, U.K.
authors.forename: Emma K
authors.initials: EK
authors.lastname: Biggs
authors.affiliation: Metabolic Research Laboratories, Wellcome Trust/MRC Institute of Metabolic Science & MRC Metabolic Diseases Unit, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge CB2 0QQ, U.K.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Gribble
authors.affiliation: Metabolic Research Laboratories, Wellcome Trust/MRC Institute of Metabolic Science & MRC Metabolic Diseases Unit, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge CB2 0QQ, U.K. fr222@cam.ac.uk.
authors.forename: Frank
authors.initials: F
authors.lastname: Reimann
mesh_terms: D000818:Animals; D006801:Humans; D045744:Cell Line, Tumor; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D052216:Glucagon-Like Peptide 1 / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D057786:Peptidomimetics / Q000627:therapeutic use
chemical_list: D052216:Glucagon-Like Peptide 1; D057786:Peptidomimetics
keywords: CRISPR; incretin; insulin