Antidiabetic effect of novel modulating peptides of G-protein-coupled kinase in experimental models of diabetes

Diabetologia
Y AnisE Ziv

Abstract

G-protein-coupled receptor kinases (GRKs) play a key role in agonist-induced desensitisation of G-protein-coupled receptors (GPCRs) that are involved in metabolic regulation and glucose homeostasis. Our aim was to examine whether small peptides derived from the catalytic domain of GRK2 and -3 would ameliorate Type 2 diabetes in three separate animal models of diabetes. Synthetic peptides derived from a kinase-substrate interaction site in GRK2/3 were initially screened for their effect on in vitro melanogenesis, a GRK-mediated process. The most effective peptides were administered intraperitoneally, utilising a variety of dosing regimens, to Psammomys obesus gerbils, Zucker diabetic fatty (ZDF) rats, or db/db mice. The metabolic effects of these peptides were assessed by measuring fasting and fed blood glucose levels and glucose tolerance. Two peptides, KRX-683(107) and KRX-683(124), significantly reduced fed-state blood glucose levels in the diabetic Psammomys obesus. In animals treated with KRX-683(124) at a dose of 12.5 mg/kg weekly for 7 weeks, ten of eleven treated animals responded with mean blood glucose significantly lower than controls (4.7+/-0.4 vs 16.8+/-0.8 mmol/l, p</=0.0001). Significant reductions in blood glucos...Continue Reading

References

Jun 1, 1978·Journal of the National Cancer Institute·E B Briles, S Kornfeld
Jun 1, 1994·The Journal of Clinical Investigation·S ReynisdottirP Arner
Oct 6, 1998·Annual Review of Biochemistry·J A PitcherR J Lefkowitz
May 14, 1999·The Journal of Clinical Endocrinology and Metabolism·K YamadaK Nonaka
Jun 1, 2000·Metabolism: Clinical and Experimental·G J Etgen, B A Oldham
Feb 7, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·R H Unger, L Orci
Feb 28, 2001·Diabetes, Obesity & Metabolism·L C Groop
Aug 8, 2001·Journal of Internal Medicine·L Groop, M Orho-Melander
Sep 14, 2001·Best Practice & Research. Clinical Endocrinology & Metabolism·A L Gloyn, M I McCarthy
Jun 4, 2002·Current Drug Targets·M H Moneva, S Dagogo-Jack
Jun 25, 2002·International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity·D L EllsworthG S Berenson
Jul 18, 2002·Nature Reviews. Drug Discovery·Vivion E F CrowleyStephen O'Rahilly
Oct 3, 2002·Neuropeptides·A A Butler, R D Cone
Nov 29, 2002·Frontiers in Bioscience : a Journal and Virtual Library·Shaoping JiLibo Yao
Dec 5, 2002·The Journal of Allergy and Clinical Immunology·L H Philipson
Jan 2, 2003·Proceedings of the National Academy of Sciences of the United States of America·Christopher J HupfeldJerrold M Olefsky
Apr 8, 2003·Current Topics in Medicinal Chemistry·Val S Goodfellow, John Saunders
Apr 24, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Radhika MuzumdarNir Barzilai
Jul 10, 2003·Annals of the New York Academy of Sciences·Ana Luisa KadekaroZalfa A Abdel-Malek
Oct 23, 2003·The Journal of Biological Chemistry·Masha Y NivHadas Reuveni

❮ Previous
Next ❯

Citations

Oct 1, 2013·European Journal of Medicinal Chemistry·Alfonso CarotenutoPietro Campiglia
Jul 23, 2011·Circulation Research·Stephen L Belmonte, Burns C Blaxall
May 12, 2006·Médecine sciences : M/S·Thierry MétayéJean-Louis Kraimps
Oct 24, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Kristoff T HomanJohn J G Tesmer
May 28, 2011·Archives of Physiology and Biochemistry·Federico MayorCristina Murga
Dec 9, 2015·Archives of Physiology and Biochemistry·Elisa LucasRocio Vila-Bedmar
Oct 9, 2015·Journal of Smooth Muscle Research = Nihon Heikatsukin Gakkai Kikanshi·Kumiko TaguchiTsuneo Kobayashi
Oct 18, 2011·Experimental Cell Research·Lada KrilovBernard Bouscarel
Jul 2, 2010·British Journal of Pharmacology·Petronila PenelaFederico Mayor
Jul 1, 2016·Journal of Medicinal Chemistry·Manuela GuccioneSilvana Grasso
Dec 31, 2016·Biomolecules & Therapeutics·Supachoke MangmoolHitoshi Kurose
Apr 29, 2005·Diabetes/metabolism Research and Reviews
Aug 10, 2005·Diabetes/metabolism Research and Reviews·Simona HefetzEleazar Shafrir
Oct 30, 2008·BioTechniques·Isaiah WexlerHadas Reuveni
Feb 1, 2019·Expert Opinion on Therapeutic Targets·Melissa Lieu, Walter J Koch
Nov 23, 2006·Physiology·Oksana Kaidanovich-Beilin, Hagit Eldar-Finkelman
Jul 23, 2015·Science Signaling·Rocio Vila-BedmarCristina Murga
Apr 21, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Rocio Vila-BedmarSonia Fernández-Veledo
Oct 23, 2003·The Journal of Biological Chemistry·Masha Y NivHadas Reuveni
Dec 13, 2018·Frontiers in Pharmacology·Supachoke MangmoolHitoshi Kurose
Aug 18, 2017·Scientific Reports·Kumiko TaguchiTsuneo Kobayashi
Dec 22, 2016·Frontiers in Cardiovascular Medicine·Daniela SorrientoGuido Iaccarino
Apr 3, 2019·International Journal of Molecular Sciences·Ersilia CipollettaGuido Iaccarino
Jan 14, 2020·Cellular and Molecular Life Sciences : CMLS·Rocío Vila-BedmarCristina Murga

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.