Differences in glucose recognition by individual rat pancreatic B cells are associated with intercellular differences in glucose-induced biosynthetic activity.

Abstract

In vitro incubated rat islet B cells differ in their individual rates of protein synthesis. The number of cells in biosynthetic activity increases with the glucose concentration. Flow cytometric monitoring of the cellular redox states indicated that islet B cells differ in their individual metabolic responsiveness to glucose. A shift from basal to increased NAD(P)H fluorescence occurred for 18% of the cells at 1 mM glucose, for 43% at 5 mM, and for 70% at 20 mM. The functional significance of this metabolic heterogeneity was assessed by comparing protein synthesis in metabolically responsive and unresponsive subpopulations, shortly after their separation by autofluorescenceactivated cell sorting. The glucose-sensitive subpopulation exhibited four-to fivefold higher rates of insulin synthesis during 60-min incubations at 2.5-10 mM glucose. Its higher biosynthetic activity was mainly caused by recruitment of cells into active synthesis and, to a lesser extent, by higher biosynthetic activity per recruited cell. Cells from the glucose-sensitive subpopulation were larger, and presented a threefold higher density of a pale secretory vesicle subtype, which is thought to contain unprocessed proinsulin. It is concluded that intercellular differences in metabolic responsiveness result in functional heterogeneity of the pancreatic B cell population. (J. Clin. Invest. 1992. 89:117-125.)

Imaging dynamic insulin release using a fluorescent zinc indicator for monitoring induced exocytotic release (ZIMIR)

“…First, we show that within intact rat islets, β cells are heterogenous in their exocytotic activity following glucose stimulation, such that only a subpopulation of β cells displays robust secretion at any one time. The above findings may reflect the metabolic heterogeneity of individual β cells (34), possibly attributable to differences in the expression of "glucose-sensing" enzymes, notably glucokinase (35), and the heterogeneity in glucose-induced cytosolic Ca 2+ ([Ca 2+ ] i ) increases previously observed in 11% of WT mouse islets (36). Interestingly, our results showed that rat β cells manifesting robust GSIS tended to aggregate in small clusters and that cells within individual clusters appeared to act together as a "secretory unit" to release insulin in synchrony.…”

Virgin Beta Cells Persist throughout Life at a Neogenic Niche within Pancreatic Islets

“…Our discovery that a population of immature beta cells persists in the islets of healthy adult mice and, possibly, humans, is also a strong testament to the significant heterogeneity that has long been known amongst beta cells (Giordano et al, 1991;Kiekens et al, 1992). Insulin-expressing Pancreatic Multipotent Progenitor cells (PMPs) were reported that are capable of extensive self-replication, self-renewal and contribute to multiple pancreatic and neural cell types (Smukler et al, 2011).…”

Insulin secretion from human beta cells is heterogeneous and dependent on cell-to-cell contacts

“…In rodents, beta cell heterogeneity was also observed in terms of metabolic, signalling [27,28] and biosynthetic activities [12,29]. Mechanisms explaining heterogeneity of beta cells are totally unknown.…”

“…The importance of homologous contacts between beta cells is further supported by the observation in rodents that the functioning of isolated beta cells is heterogeneous [9][10][11][12][13]. For instance, beta cells respond unequally to glucose stimulation in terms of insulin secretion and biosynthetic activity [12,14,15].…”

“…For instance, beta cells respond unequally to glucose stimulation in terms of insulin secretion and biosynthetic activity [12,14,15]. It has been suggested that intercellular contacts coordinate the functioning of beta cells by homogenising and synchronising their activities.…”