Intravascular Follistatin gene delivery improves glycemic control in a mouse model of type 2 diabetes.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Jonathan R DaveyPaul Gregorevic

Abstract

Type 2 diabetes (T2D) manifests from inadequate glucose control due to insulin resistance, hypoinsulinemia, and deteriorating pancreatic β-cell function. The pro-inflammatory factor Activin has been implicated as a positive correlate of severity in T2D patients, and as a negative regulator of glucose uptake by skeletal muscle, and of pancreatic β-cell phenotype in mice. Accordingly, we sought to determine whether intervention with the Activin antagonist Follistatin can ameliorate the diabetic pathology. Here, we report that an intravenous Follistatin gene delivery intervention with tropism for striated muscle reduced the serum concentrations of Activin B and improved glycemic control in the db/db mouse model of T2D. Treatment reversed the hyperglycemic progression with a corresponding reduction in the percentage of glycated-hemoglobin to levels similar to lean, healthy mice. Follistatin gene delivery promoted insulinemia and abundance of insulin-positive pancreatic β-cells, even when treatment was administered to mice with advanced diabetes, supporting a mechanism for improved glycemic control associated with maintenance of functional β-cells. Our data demonstrate that single-dose intravascular Follistatin gene delivery can ame...Continue Reading

References

Sep 2, 1966·Science·K P HummelD L Coleman
May 13, 1999·The Journal of Endocrinology·D M de KretserD J Phillips
Jul 19, 2001·Proceedings of the National Academy of Sciences of the United States of America·S J Lee, A C McPherron
Dec 28, 2002·Diabetes·Alexandra E ButlerPeter C Butler
Jun 18, 2003·Cell·Yigong Shi, Joan Massagué
Jul 27, 2004·Nature Medicine·Paul GregorevicJeffrey S Chamberlain
Jul 31, 2004·Journal of the American Society of Nephrology : JASN·Markus LassilaKarin A M Jandeleit-Dahm
Nov 25, 2004·Diabetes·Gordon C Weir, Susan Bonner-Weir
Oct 4, 2007·Proceedings of the National Academy of Sciences of the United States of America·Kristian L JonesDavid J Phillips
May 16, 2008·Proceedings of the National Academy of Sciences of the United States of America·Philippe BertolinoCarlos F Ibáñez
Apr 7, 2010·Science Translational Medicine·Janaiah KotaBrian K Kaspar
Jan 6, 2011·American Journal of Physiology. Endocrinology and Metabolism·Masashi NakataniKunihiro Tsuchida
Mar 20, 2012·Cell·Frances M Ashcroft, Patrik Rorsman
Jun 20, 2012·The Journal of Cell Biology·Catherine E WinbanksPaul Gregorevic
Jun 30, 2012·Nature Methods·Johannes SchindelinAlbert Cardona
Jan 11, 2013·Experimental Diabetes Research·Hui WuMark P Hedger
Feb 8, 2013·The New England Journal of Medicine·Yuval Dor, Benjamin Glaser
Jul 19, 2013·The Journal of Clinical Investigation·Shuangli GuoRoland Stein
Jan 1, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Justin L ChenPaul Gregorevic
Feb 11, 2014·Journal of the American Society of Nephrology : JASN·Jay C JhaKarin A Jandeleit-Dahm
Oct 18, 2014·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jerry R MendellBrian K Kaspar
Feb 14, 2015·Molecular Therapy : the Journal of the American Society of Gene Therapy·Chunxia ZhaoXiao Xiao
Dec 30, 2015·Molecular and Cellular Biology·Doriane RipochePhilippe Bertolino
Dec 30, 2015·The Journal of Clinical Endocrinology and Metabolism·Francesca CintiDomenico Accili
Jul 22, 2016·Science Translational Medicine·Catherine E WinbanksPaul Gregorevic
Nov 11, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Melissa M PageJames D Johnson
Apr 6, 2018·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Rajan SinghSrinivasa T Reddy
May 31, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sarah A TerseyRaghavendra G Mirmira
Jun 6, 2018·Nature Medicine·Rongya TaoMorris F White

❮ Previous
Next ❯

Citations

Aug 5, 2020·Nature Metabolism·Robyn M MurphyMark A Febbraio
Dec 1, 2020·Frontiers in Physiology·Adam HaggKelly L Walton

❮ 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.