Zn(II) ions co-secreted with insulin suppress inherent amyloidogenic properties of monomeric insulin

The Biochemical Journal
Andra NoormägiPeep Palumaa

Abstract

Insulin, a 51-residue peptide hormone, is an intrinsically amyloidogenic peptide, forming amyloid fibrils in vitro. In the secretory granules, insulin is densely packed together with Zn(II) into crystals of Zn(2)Insulin(6) hexamer, which assures osmotic stability of vesicles and prevents fibrillation of the peptide. However, after release from the pancreatic beta-cells, insulin dissociates into active monomers, which tend to fibrillize not only at acidic, but also at physiological, pH values. The effect of co-secreted Zn(II) ions on the fibrillation of monomeric insulin is unknown, however, it might prevent insulin fibrillation. We showed that Zn(II) inhibits fibrillation of monomeric insulin at physiological pH values by forming a soluble Zn(II)-insulin complex. The inhibitory effect of Zn(II) ions is very strong at pH 7.3 (IC(50)=3.5 microM), whereas at pH 5.5 it progressively weakens, pointing towards participation of the histidine residue(s) in complex formation. The results obtained indicate that Zn(II) ions might suppress fibrillation of insulin at its release sites and in circulation. It is hypothesized that misfolded oligomeric intermediates occurring in the insulin fibrillation pathway, especially in zinc-deficient con...Continue Reading

References

Oct 19, 1976·Biochemistry·P D JeffreyL W Nichol
Nov 1, 1986·Diabetic Medicine : a Journal of the British Diabetic Association·J BrangeC Kühl
Jun 20, 1972·Biochemistry·M J Burke, M A Rougvie
May 1, 1966·The American Journal of Medicine·M G AdamG G Dodson
Feb 1, 1993·Biophysical Journal·M C FosterI Atwater
May 1, 1997·Journal of Pharmaceutical Sciences·J BrangeE Rasmussen
May 8, 1998·Seminars in Cell & Developmental Biology·J W CreemersJ C Hutton
Jun 19, 1998·Current Opinion in Structural Biology·G Dodson, D Steiner
Dec 6, 2000·Protein Science : a Publication of the Protein Society·M BouchardC V Robinson
Apr 30, 2002·Hormone Research·Mikael Knip
Oct 1, 2003·Biochemistry·Atta AhmadAnthony L Fink
Jan 23, 2004·The Journal of Biological Chemistry·Atta AhmadAnthony L Fink
Jun 17, 2004·Experimental Diabesity Research·Donald F Steiner
Oct 26, 2005·The Journal of Biological Chemistry·Atta AhmadAnthony L Fink
Jul 18, 2006·Cellular and Molecular Life Sciences : CMLS·J ShafqatH Jörnvall
Feb 9, 2007·Journal of Neurochemistry·Dominic M Walsh, Dennis J Selkoe
Nov 28, 2007·Journal of Biomolecular NMR·Wojciech BocianLech Kozerski
May 21, 2008·Journal of Molecular Neuroscience : MN· Bharathi, K S J Rao
Jul 5, 2008·Biophysical Journal·M I SmithC J Roberts
Jul 26, 2008·Proteins·Arpan NayakGeorges Belfort
Aug 27, 2009·Proceedings of the National Academy of Sciences of the United States of America·K LemaireF C Schuit
Sep 1, 2009·Biochemistry·Tue RasmussenMarco van de Weert
Oct 30, 2009·Proceedings of the National Academy of Sciences of the United States of America·Magdalena I IvanovaDavid Eisenberg
Dec 29, 2009·Biochemical and Biophysical Research Communications·Hans JörnvallJan Johansson

❮ Previous
Next ❯

Citations

Aug 22, 2012·European Biophysics Journal : EBJ·Sarah R ShefticAndrei T Alexandrescu
Apr 21, 2012·Diabetology & Metabolic Syndrome·R JayawardenaP Katulanda
Apr 24, 2013·Journal of Peptide Science : an Official Publication of the European Peptide Society·Ann TiimanVello Tõugu
Nov 16, 2011·Journal of Peptide Science : an Official Publication of the European Peptide Society·Andra NoormägiPeep Palumaa
Sep 28, 2012·The Biochemical Journal·Michael LandrehHans Jörnvall
Jan 28, 2012·Biochemical and Biophysical Research Communications·Michael LandrehHans Jörnvall
Dec 30, 2014·Analytical Chemistry·Yu WangThomas Peter Burg
Oct 31, 2018·Physical Chemistry Chemical Physics : PCCP·Mantas ZiaunysVytautas Smirnovas
Jan 2, 2019·JAD Reports·Steffi WitterAgo Samoson
Dec 31, 2019·Journal of Alzheimer's Disease : JAD·Steffi WitterRaiker Witter
Jun 4, 2014·Metallomics : Integrated Biometal Science·Julia GavrilovaPeep Palumaa
Feb 6, 2021·Biophysical Journal·Kevin PounotGiorgio Schirò
Nov 9, 2011·Langmuir : the ACS Journal of Surfaces and Colloids·Yisheng XuPaul L Dubin
Nov 16, 2019·The Journal of Physical Chemistry. B·Saumyak MukherjeeBiman Bagchi
Aug 24, 2019·The Journal of Physical Chemistry. B·Li Hung C ChungOlaf J Rolinski

❮ 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.

Related Papers

Biochemical and Biophysical Research Communications
Charlotte NereliusHans Jörnvall
Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry
Bruno AliesPeter Faller
Journal of the American College of Nutrition
A B Chausmer
Diabetes Care
M M EngelgauW H Herman
© 2021 Meta ULC. All rights reserved