# Proteomic predictors of individualized nutrient-specific insulin secretion in health and disease

Article · Kolic J, Sun WG, Cen HH, Ewald JD, Rogalski JC, Sasaki S, Sun H, Rajesh V, Xia YH, Moravcova R, Skovsø S, Spigelman AF, Manning Fox JE, Lyon J, Beet L, Xia J, Lynn FC, Gloyn AL, Foster LJ, MacDonald PE, Johnson JD

- Archive id: doi:10.1016/j.cmet.2024.06.001
- Published: 2024-07-01
- Venue: Cell metabolism
- DOI: https://doi.org/10.1016/j.cmet.2024.06.001
- PMID: 38959864
- PMCID: PMC11250105
- Citations: 65
- Source URL: https://doi.org/10.1016/j.cmet.2024.06.001
- PDF: https://europepmc.org/articles/PMC11250105/pdf
- Provenance: europepmc

## Abstract

Population-level variation and mechanisms behind insulin secretion in response to carbohydrate, protein, and fat remain uncharacterized. We defined prototypical insulin secretion responses to three macronutrients in islets from 140 cadaveric donors, including those with type 2 diabetes. The majority of donors' islets exhibited the highest insulin response to glucose, moderate response to amino acid, and minimal response to fatty acid. However, 9% of donors' islets had amino acid responses, and 8% had fatty acid responses that were larger than their glucose-stimulated insulin responses. We leveraged this heterogeneity and used multi-omics to identify molecular correlates of nutrient responsiveness, as well as proteins and mRNAs altered in type 2 diabetes. We also examined nutrient-stimulated insulin release from stem cell-derived islets and observed responsiveness to fat but not carbohydrate or protein-potentially a hallmark of immaturity. Understanding the diversity of insulin responses to carbohydrate, protein, and fat lays the groundwork for personalized nutrition.

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Gene & Cell Therapy](https://space-kitty.com/topics/gene-cell-therapy)

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