NIH Reporter #2R01DK106412-10

Emergent Multi-Cellular Properties Regulating Pancreatic Islet Function

This NIH-funded project investigates the heterogeneity of insulin-secreting β-cells in pancreatic islets to understand their adaptation and dysfunction in type 2 diabetes. The research focuses on molecular characterization, cell fate under metabolic stress, and gene activity roles, aiming to identify therapeutic targets to improve islet function in diabetes.

Description

Type 2 diabetes mellitus (T2DM) is caused by a failure of insulin-secreting β-cells to secrete sufficient insulin following increased insulin resistance under metabolic stress. This project aims to understand the characteristics of heterogeneous β-cell populations within the islet to gain fundamental understanding of how islet function is regulated in both healthy conditions and under metabolic stress. The research includes characterizing molecular properties underlying heterogeneous β-cell glucose responses, determining the fate of β-cells under metabolic stress, and determining the role of activity-responsive genes in maintaining β-cell heterogeneity. Therapeutic agents targeting specific populations of 'functionally adapted' β-cells may provide new ways to control the islet under pathogenic conditions.

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