Abstract

The pancreatic beta cell functions as a key regulator of blood glucose levels by integrating a variety of signals in response to changing metabolic demands. Variations in beta cell identity that translate into functionally different subpopulations represent an interesting mechanism to allow beta cells to efficiently respond to diverse physiological and pathophysiological conditions. Recently, there is emerging evidence that morphological and functional differences between beta cells exist. Furthermore, the ability of novel single cell technologies to characterize the molecular identity of individual beta cells has created a new era in the beta cell field. These studies are providing important novel information about the origin of beta cell heterogeneity, the type and proportions of the different beta cell subpopulations, as well as their intrinsic properties. Furthermore, characterization of different beta cell subpopulations that could variably offer protection from or drive progression of diabetes has important clinical implications in diabetes prevention, beta cell regeneration and stem cell treatments. In this review, we will assess the evidence that supports the existence of heterogeneous populations of beta cells and the factors that could influence their formation. We will also address novel studies using islet single cell analysis that have provided important information toward understanding beta cell heterogeneity and discuss the caveats that may be associated with these new technologies.

Highlights

  • The pancreatic beta cell is an essential endocrine cell type whose identity has been traditionally defined by its function: producing, storing and secreting insulin

  • We will discuss the evidence supporting the existence of beta cell heterogeneity, the mechanisms influencing its development, and its functional relevance

  • Beta cell heterogeneity has recently received increasing attention, and studies are emerging that challenge our understanding of beta cell identity

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Summary

Heterogeneity of the Pancreatic Beta Cell

Reviewed by: Girdhari Lal, National Centre for Cell Science, India Jantje Mareike Gerdes, Helmholtz Zentrum München, Germany. The ability of novel single cell technologies to characterize the molecular identity of individual beta cells has created a new era in the beta cell field. These studies are providing important novel information about the origin of beta cell heterogeneity, the type and proportions of the different beta cell subpopulations, as well as their intrinsic properties. We will assess the evidence that supports the existence of heterogeneous populations of beta cells and the factors that could influence their formation. We will address novel studies using islet single cell analysis that have provided important information toward understanding beta cell heterogeneity and discuss the caveats that may be associated with these new technologies

INTRODUCTION
EXAMPLES OF CELL HETEROGENEITY
BETA CELL HETEROGENEITY
BETA CELL HETEROGENEITY DURING DEVELOPMENT
MORPHOLOGICAL HETEROGENEITY
FUNCTIONAL HETEROGENEITY
MOLECULAR HETEROGENEITY
CONTEXT DEPENDENT FACTORS INFLUENCE HETEROGENEITY
Findings
BETA CELL HETEROGENEITY AND EFFECTS ON DISEASE PROGRESSION AND THERAPIES
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