bioRxiv : the preprint server for biologyOct 3, 2025

Targeted glycophagy therapy reverses diabetic heart disease in mice and human heart tissues

Regenerative Health Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 7, 2026

Abstract

Gabarapl1 gene delivery treatment improved cardiac diastolic dysfunction in type 2 diabetic mice and human heart organoids.

Diabetic heart disease is linked to early impaired diastolic relaxation.
Glycophagy, the process of degrading glycogen, is disrupted in the diabetic heart.
The glycogen receptor protein STBD1 is mobilized in response to metabolic challenges.
Deficiency of Gabarapl1 is associated with diastolic dysfunction in diabetes.
Glycophagy dysregulation may serve as a mechanism for diabetic heart disease.

Simplified

Diabetic heart disease is highly prevalent and is associated with the early development of impaired diastolic relaxation. The mechanisms of diabetic heart disease are poorly understood and it is a condition for which there are no targeted therapies. Recently, disrupted glycogen-autophagy (glycophagy) and glycogen accumulation have been identified in the diabetic heart. Glycophagy involves glycogen receptor binding and linking with an ATG8 protein to locate and degrade glycogen within an intracellular phago-lysosome. Here we show that glycogen receptor protein STBD1 (starch-binding-domain-protein-1) is mobilized early in the cardiac glycogen response to metabolic challenge, and that deficiency of a specific ATG8 family protein, Gabarapl1 (γ-aminobutyric-acid-receptor-associated-protein-like-1) is associated with diastolic dysfunction in diabetes. Gabarapl1 gene delivery treatment remediated cardiomyocyte and cardiac diastolic dysfunction in type 2 diabetic mice and diastolic performance of 'diabetic' human iPSC-derived cardiac organoids. We identify glycophagy dysregulation as a mechanism and potential treatment target for diabetic heart disease. in vivo

Funding

Competing interests

COMPETING INTERESTS The authors declare no competing financial interests.

PubMed

Targeted glycophagy therapy reverses diabetic heart disease in mice and human heart tissues

Abstract

Funding

Competing interests

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Abstract

Funding

Competing interests

Related papers

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week: