PXD044236

PXD044236 is an original dataset announced via ProteomeXchange.

Title	Title Page Cardiac Gene Therapy Rescues Diabetic Cardiomyopathy and Lowers Blood Glucose
Description	Diabetic cardiomyopathy, an increasingly global epidemic and a major cause of heart failure with preserved ejection fraction (HFpEF), is associated with hyperglycemia, insulin resistance, and intra-cardiomyocyte calcium mishandling. Here we identify that, in db/db mice with type 2 diabetes induced HFpEF, abnormal remodeling of cardiomyocyte transverse-tubule microdomains occurs with downregulation of the membrane scaffolding protein cardiac bridging integrator 1 (cBIN1). Transduction of cBIN1 by AAV9 gene therapy can restore transverse-tubule microdomains to normalize intracellular distribution of calcium handling proteins and, surprisingly, glucose transporter 4 (GLUT4). Cardiac proteomics revealed that AAV9-cBIN1 normalizes components of calcium handling and GLUT4 translocation machineries. Functional studies further identified that AAV9-cBIN1 normalizes insulin-dependent glucose uptake in diabetic cardiomyocytes. Phenotypically, AAV9-cBIN1 rescues cardiac lusitropy, improves exercise intolerance, and ameliorates hyperglycemia in diabetic mice. Restoration of transverse-tubule microdomains can improve cardiac function in the setting of diabetic cardiomyopathy, and also improve systemic glycemic control.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:06:37.123.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ryan Bia
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-31 11:23:26	ID requested
1	2023-10-24 10:31:27	announced
⏵ 2	2023-11-14 09:06:46	announced	2023-11-14: Updated project metadata.

Li J, Richmond B, Cluntun AA, Bia R, Walsh MA, Shaw K, Symons JD, Franklin S, Rutter J, Funai K, Shaw RM, Hong T, Cardiac gene therapy treats diabetic cardiomyopathy and lowers blood glucose. JCI Insight, 8(18):(2023) [pubmed]

submitter keyword: calcium handling,transverse-tubule microdomain, gene therapy, glucose uptake, diabetic cardiomyopathy

Sarah Franklin
contact affiliation	Dr. Sarah Franklin, Principal Investigator, CVRTI, University of Utah
contact email	sarah.franklin@utah.edu
lab head
Ryan Bia
contact affiliation	University of Utah
contact email	ryan.bia@utah.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD044236
     1. Label: PRIDE project
     2. Name: Title Page Cardiac Gene Therapy Rescues Diabetic Cardiomyopathy and Lowers Blood Glucose