Heterogeneity in Pancreatic β-cell Population

Abstract

All pancreatic beta-cells are identified by specific morphological characteristics. Similarity in microscopic features is not necessarily associated with identity in functional properties. In vitro studies on isolated rat beta-cells have indicated intercellular differences in the threshold for glucose-induced shifts in metabolic redox state. The cellular heterogeneity in glucose sensitivity results in a dose-dependent recruitment of glucose-exposed beta-cells into biosynthetic and secretory activities. The molecular basis of this diversity is not known. Indirect evidence supports the concept that the in situ pancreatic beta-cell population is also composed of functionally diverse subpopulations. The heterogeneity in glucose responsiveness is expected to create subpopulations of beta-cells with either constant, fluctuating, or occasional glucose-dependent functions; whether any subpopulation is preferentially responsive to other regulatory factors and/or committed to other activities is unknown. Morphological markers may help identify beta-cell subpopulations in situ and quantify their size in conditions known to affect total beta-cell mass or function. The concept of a functionally heterogeneous beta-cell population influences views on the role of pancreatic beta-cells in health and disease.

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.…”

Emergent global oscillations in heterogeneous excitable media: The example of pancreaticβcells

“…Their heterogeneity has been made manifest in studies demonstrating differing rates among β cells of insulin synthesis and secretion [38][39][40][41][42], of glucose metabolism [43], of changes in calcium concentration [44,45], and of changes in electrical activity [46]. Physiologists have suspected the importance of this variability [47]. β cell oscillations, or bursts, are more complex than the simple oscillations of a van der Pol-FitzHugh-Nagumo type relaxation oscillator, but the basic mechanism that diversity provokes the emergence of oscillations remains the same, and provides a qualitative explanation for the emergence of global oscillations in the β cells of the mammalian pancreas.…”

Sialylated form of the neural cell adhesion molecule (NCAM): a new tool for the identification and sorting of beta-cell subpopulations with different functional activity.

“…The concept of ␤-cell heterogeneity proposes that pancreatic ␤-cells differ in their individual sensitivity to glucose (22) and are recruited when glucose concentration increases (23). Because the most responsive ␤-cells are those that are the most metabolically active, it is possible to sort the ␤-cell subpopulations according to their NAD(P)H content (22).…”