β-cell Heterogeneity: The Key to β-cell Replacement Therapy.
Cellular heterogeneity is crucial for organisms to adapt to their environmental changes. It provides the morphological, functional and molecular diversity that allows tissues and organs to respond to stressors and maintain cell integrity.
Pancreatic islets of Langer hans are cell clusters that play a key role in glucose homeostasis. Among the five hormone secretingislet endocrine cells (insulin secreting β-cells, glucagon secreting α-cells, somatostatin secreting δ-cells, pancreatic polypeptide secreting PP-cells, and ghrelin secreting ε-cells), β-cells are specialized glucose sensors that respond to increased insulin demand during physiological or pathophysiological conditions.
Since the 1960s, rodent and human studies have shown that seemingly identical β-cells can be grouped into morphological and functional subtypes. For
instance, a recent study in mice reported that proliferative and mature β-cells can be distinguished by their expression of Flattop.
Another study in mice, grouped a minor β-cell population (1-10%) as hub cells being different from
non-hub (follower) cells by their electrical-coupling capacity resulting in an organized insulin secretion. Understanding the mechanisms behind β-cell heterogeneity within or between islets can also be used as a therapeutic approach for β-cell survival. Indeed, a group of novel β-cells with lower granularity and
stem-like feature has been reported to be protected during type 1 diabetes development.
In parallel to rodent studies, several groups identified human β-cell subtypes by using technological advances. For instance, by using CyTOF
to study at a single cell level, β-cells from multiple donors were grouped into three main populations based on
their proliferation, maturation and several reported heterogeneity
Pancreas Open J. 2018; 2(1): e10-e11. doi: 10.17140/POJ-2-e009