Proteomic predictors of individualized nutrient-specific insulin secretion in health and disease.
Cell Metab
; 36(7): 1619-1633.e5, 2024 Jul 02.
Article
em En
| MEDLINE
| ID: mdl-38959864
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ilhotas Pancreáticas
/
Proteômica
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Diabetes Mellitus Tipo 2
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Secreção de Insulina
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Insulina
Limite:
Adult
/
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Cell Metab
Assunto da revista:
METABOLISMO
Ano de publicação:
2024
Tipo de documento:
Article