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Heterogeneous endocrine cell composition defines human islet functional phenotypes.

Carmella Evans-Molina^{1,2,3,4,5,6,7,8}, Yasminye D Pettway^9,8, Diane C Saunders^10,8

¹Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Biorxiv : the Preprint Server for Biology

|November 28, 2024

Summary

This summary is machine-generated.

Human islet cell composition varies significantly, impacting hormone secretion and type 2 diabetes risk. Delta cell abundance showed the strongest link to insulin secretion and diabetes genetic risk.

Keywords:

Human islets T1D T2D genetic risk score alpha cells beta cells delta cells glucagon secretion insulin secretion

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Area of Science:

Endocrinology
Genetics
Metabolic Diseases

Background:

The Integrated Islet Distribution Program (IIDP) provides standardized human islet preparations for research.
Understanding human islet heterogeneity is crucial for diabetes research and therapeutic development.

Purpose of the Study:

To analyze the heterogeneity of human islet cell composition in non-diabetic donors.
To investigate associations between islet cell composition, hormone secretion, and genetic factors related to type 2 diabetes (T2D).

Main Methods:

Phenotyping and genotyping of human islets from 299 organ donors without diabetes.
Analysis pipeline integrating multiple data types to assess islet cell composition and secretory traits.

Main Results:

Substantial heterogeneity in islet cell composition (alpha, beta, delta cells) was observed.
Islet cell composition was associated with hormone secretory traits, sex, race/ethnicity, ancestry, and T2D genetic risk.
Delta cell abundance showed the strongest association with insulin secretion and T2D genetic risk score (GRS).

Conclusions:

Human islet heterogeneity is linked to diverse factors including genetics and donor characteristics.
Delta cell abundance is a key factor in insulin secretion and T2D risk, suggesting potential therapeutic targets.
Findings inform strategies for personalized medicine and beta cell replacement therapy in diabetes.