REVIEW article
Front. Endocrinol.
Sec. Diabetes: Molecular Mechanisms
Diabetes Associated Pericyte Metabolic Signatures and Pathogenesis of Diabetic Retinopathy
Provisionally accepted- 1Indiana University Indianapolis, Indianapolis, United States
- 2University of Wisconsin-Madison School of Medicine and Public Health, Madison, United States
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Pericytes are metabolically active perivascular supporting cells. They are essential for establishing and maintaining the inner blood retinal barrier and retinal neurovascular homeostasis. In diabetic retinopathy, the chronic hyperglycemic environment adversely affects pericyte functions including their glucose flux and metabolism. The early alterations in pericyte metabolic signatures during diabetes make them susceptible as an early damage target. Altered pericyte glucose flux through the polyol pathway, pentose phosphate pathway, hexosamine biosynthesis pathway, protein kinase C pathway, and advanced glycated end products pathway are responsible for mitochondrial dysfunction, inflammation, and oxidative stress. These metabolic changes in pericytes regulate vascular blood flow and tight junctions' integrity leading to vascular dysfunction and disease progression. This review aims to discuss the current understanding of pericyte metabolic signatures and altered glucose metabolism under hyperglycemic conditions like those present in diabetes. We also aim to highlight the need for further investigation of how pericyte metabolic activities, particularly among pericyte subtypes of the retina and other organs, are coordinated. This knowledge will help to further our understanding of how to preserve the blood tissue barrier and its function, and to prevent not only diabetic retinopathy but also vascular dysfunction in other organs impacted by diabetes.
Keywords: diabetes, Diabetic Retinopathy, Metabolism, neurovascular unit, Pericytes
Received: 19 Dec 2025; Accepted: 16 Feb 2026.
Copyright: © 2026 Carrillo, Belecky-Adams and Sheibani. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Casandra Carrillo
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
