Sex-specific efficacy of curcumin-loaded nanoparticles and insulin for ocular-cardiac complications in type 2 diabetes mice

Swetha R Allamreddy; Raghu Ganugula; Meenakshi Arora; Sabrina Ingram; Subhash Dwivedi; Richard Friend; Rita Basu; M N V Ravi Kumar

doi:10.1016/j.isci.2026.116594

Sex-specific efficacy of curcumin-loaded nanoparticles and insulin for ocular-cardiac complications in type 2 diabetes mice

iScience. 2026 Jul 2;29(7):116594. doi: 10.1016/j.isci.2026.116594. eCollection 2026 Jul 17.

Authors

Swetha R Allamreddy^{1

2

3}, Raghu Ganugula^{1

2

3

4}, Meenakshi Arora^{1

2

3

4}, Sabrina Ingram¹, Subhash Dwivedi¹, Richard Friend⁵, Rita Basu⁶, M N V Ravi Kumar^{1

2

3

4

7

8}

Affiliations

¹ The Center for Convergent Bioscience and Medicine (CCBM), The University of Alabama, Tuscaloosa, AL 35401, USA.
² Department of Translational Science and Medicine, College of Community Health Sciences, The University of Alabama, Tuscaloosa, AL 35401, USA.
³ Alabama Life Research Institute, The University of Alabama, Tuscaloosa, AL 35401, USA.
⁴ Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL 35401, USA.
⁵ Family, Internal, and Rural Medicine, College of Community Health Sciences, The University of Alabama, Tuscaloosa, AL 35401, USA.
⁶ Division of Endocrinology, Diabetes, and Metabolism, School of Medicine, Marnix E. Heersink School of Medicine, The University of Alabama, Birmingham, AL 35294, USA.
⁷ Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
⁸ Nephrology Research and Training Center, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

Abstract

Current Type 2 diabetes therapies inadequately address multi-organ complications. We evaluated bivalent nanoparticles encapsulating curcumin, combined with insulin, against diabetic complications. Our data indicate shared pathophysiological mechanisms driving the association between retinal and cardiac injury, specifically systemic inflammation and mitochondrial dysregulation across both organs. Retinal stress (HIF1α, REDD1, VEGF) preceded cardiac remodeling, characterized by lymphangiogenesis (LYVE1, VEGFR3) and impaired PPARα/ PGC1α signaling. Furthermore, we identified a strong pathological correlation between intraocular and systemic blood pressures as an in-vivo physiological readout of widespread vascular dysregulation. While males exhibited an earlier onset, females progressed more rapidly to complications. The combination therapy proved highly effective in both sexes. While females exhibited a more pronounced reduction in systemic inflammation and pathological pressure correlation, males demonstrated robust metabolic and structural preservation. These findings highlight ocular hemodynamics as an early physiological indicator of cardiac complications, supporting this sex-specific nanotherapeutic strategy, combined with insulin, to mitigate diabetic complications.

Keywords: curcumin nanoparticles; diabetic complications; eye-heart axis; inflammation; lymphangiogenesis; pressure correlation; sex-differences.