A beta cell subset with enhanced insulin secretion and glucose metabolism is reduced in type 2 diabetes

Localization and function of multivesicular-bodies that release exosomes in islet cells: dysregulation during type-2 diabetes

“…The decrease in density of MVBs and ISGs in diabetic human islet cells is maybe because of their non-functionality. This might reflect decreased synthesis and secretion from ISGs (35) or MVBs (9,50) as shown previously.…”

“…A subset of β-cells with high expression of CD63 shows enhanced insulin secretion. This subset was diminished in case of T2D (50). Similarly, islets from T2D patients had decreased secretion of EVs due to increased islet amyloids which could be reversed by adding EVs derived from healthy patients in vitro (9).…”

Differential CpG methylation atNnatin the early establishment of beta cell heterogeneity

“…Interestingly, both embryonic and adult NNAT + beta cells were enriched for Npy and adult NNAT + beta cells had lower UCN3 protein, suggesting that these cells were not fully matured. NNAT + beta cells however had significantly higher insulin content, suggesting a possible, at least partial, overlap with the recently-described "CD63 hi " population recently defined by [29], and the "bHI" population described by [11].…”

“…Early reports [12][13][14], and more recent studies based on single cell transcriptomic profiling [15][16][17], electrophysiology [18] and functional imaging [19][20][21][22] have demonstrated functional heterogeneity amongst individual beta cells (reviewed in [23,24]). Identified subpopulations have been associated with known markers or maturation states (Flattop/Cfap126 [21], PSA-NCAM [25], CD81 [26], CD24 [11,27], TH [10], NPY [28], CD63 [29]), are 'virgin' beta cells [30] or are defined by their roles in coordinating islet-wide Ca 2+ dynamics (e.g. 'hubs' [19], 'leaders' [20] [31] and 'first responders' [32]).…”

“…The features underlying beta cell heterogeneity include pathways governing glucose sensing and metabolism [19][20][21]36] insulin content and secretory competence [9,18,30,37,38] and cilia activity and localisation within the islet [31]. Recently, two discrete populations of "CD63 hi " and "CD63 lo " cells have been described [29], with "CD63 hi " cells enriched for CD63 and for insulin content and glucosestimulated insulin secretion (GSIS). Epigenomically-defined (by histone methylation, H3K27me3) CD24-positive "bHI" beta cells with enhanced insulin content and GSIS [11] may partly overlap the "CD63 hi " population [29].…”