Heterogeneity of the Pancreatic Beta Cell

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.

Episodic β‐cell death and dedifferentiation during diet‐induced obesity and dysglycemia in male mice

“…Recent studies have identified distinct subpopulations of b cells in mouse and human islets (24)(25)(26)(27). The heterogeneity of b cells lends credence to the notion that different b cell populations (or subsets) may exhibit differing capacities for proliferation, stress responsiveness, and identity maintenance (28). Whether specific subpopulations of b cells are accountable for the cell death and dedifferentiation seen in our study is open to speculation, but our findings suggest the need to further interrogate the cellular subpopulations affected during the course of obesity and glucose intolerance.…”

Beta-cell hubs maintain Ca2+ oscillations in human and mouse islet simulations

“…57-59 Within an islet model, we picked all maximal conductance parameter values, for both hubs and non-hubs, from a normal distribution with mean value equal to original parameter value given in Cha et al 43 and standard deviation equal to 20% of the mean value . This allowed us to account for variability and parameter uncertainty in our simulation results.…”

Single molecule approaches for studying gene regulation in metabolic tissues

“…For example liver energy‐demanding biosynthetic processes that include protein secretion and gluconeogenesis are allocated to the lobule regions that receive more oxygen. The islets of Langerhans also exhibit several sources of spatial heterogeneity related to the position of cells relative to blood vessels, the paracrine interactions with other cells types and the distances from the islet periphery . These spatial sources of variations can potentially give rise to distinct sub‐populations with specific allocation of function to distinct islet niches .…”