Open Biology· 2026Q1
Perspectives on tissue-selective insulin derivatives
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- Q1SCImago
- 2026year
Short summary
New insulin derivatives are being engineered to target specific tissues (liver, muscle, brain, adipose), mimicking endogenous insulin's physiological distribution and potentially overcoming current therapy limitations.
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Key points
- Current insulin therapies lack the physiological tissue distribution of endogenous insulin.
- Emerging strategies include molecular engineering, receptor isoform modulation, and targeted delivery.
- Specific strategies focus on hepato-preferential, muscle-directed, brain-targeted, and adipose-modulating actions.
- Challenges persist in achieving tissue selectivity while maintaining whole-body metabolic control.
AI-generated from the title and abstract; the full text is not read.
Abstract
Abstract Insulin is a central regulator of metabolic homoeostasis with diverse, tissue-specific actions across multiple organs. Despite major advances in insulin formulations, current therapies rely on systemic delivery and do not reproduce the physiological distribution of endogenous insulin, resulting in non-physiological tissue exposure and associated metabolic limitations. In this perspective, we discuss emerging strategies aimed at achieving tissue-selective insulin action, including molecular engineering of insulin analogues, modulation of insulin receptor isoform specificity and targeted delivery approaches. Attention is given to hepato-preferential, muscle-directed, brain-targeted and adipose-modulating strategies, highlighting their mechanistic basis, therapeutic potential and inherent limitations. While proof of principle has been established for several approaches, challenges remain in balancing tissue selectivity with whole-body metabolic control. Advances in protein design and delivery technologies may ultimately enable the development of next-generation insulin therapies that better mimic physiological insulin action and improve clinical outcomes in metabolic and neurodegenerative diseases.
The authors' abstract, as published at the source. Open Biology, 2026 · DOI ↗
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Field: Endocrinology, Diabetes and Metabolism
Endocrinology, Diabetes and MetabolismMedicine