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Human islets contain four distinct subtypes of ? cells.

ABSTRACT: Human pancreatic islets of Langerhans contain five distinct endocrine cell types, each producing a characteristic hormone. The dysfunction or loss of the insulin-producing ? cells causes diabetes mellitus, a disease that harms millions. Until now, ? cells were generally regarded as a single, homogenous cell population. Here we identify four antigenically distinct subtypes of human ? cells, which we refer to as ?1-4, and which are distinguished by differential expression of ST8SIA1 and CD9. These subpopulations are always present in normal adult islets and have diverse gene expression profiles and distinct basal and glucose-stimulated insulin secretion. Importantly, the ? cell subtype distribution is profoundly altered in type 2 diabetes. These data suggest that this antigenically defined ? cell heterogeneity is functionally and likely medically relevant.

SUBMITTER: Dorrell C

PROVIDER: S-EPMC4942571 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Human islets contain four distinct subtypes of β cells.

Dorrell Craig C Schug Jonathan J Canaday Pamela S PS Russ Holger A HA Tarlow Branden D BD Grompe Maria T MT Horton Tamara T Hebrok Matthias M Streeter Philip R PR Kaestner Klaus H KH Grompe Markus M

Nature communications 20160711

Human pancreatic islets of Langerhans contain five distinct endocrine cell types, each producing a characteristic hormone. The dysfunction or loss of the insulin-producing β cells causes diabetes mellitus, a disease that harms millions. Until now, β cells were generally regarded as a single, homogenous cell population. Here we identify four antigenically distinct subtypes of human β cells, which we refer to as β1-4, and which are distinguished by differential expression of ST8SIA1 and CD9. These ...[more]

PMID: 27399229

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Project description:microRNAs (miRNAs) play an important role in pancreatic development and adult ?-cell physiology. Our hypothesis is based on the assumption that each islet cell type has a specific pattern of miRNA expression. We sought to determine the profile of miRNA expression in ?-and ?-cells, the main components of pancreatic islets, because this analysis may lead to a better understanding of islet gene regulatory pathways. Highly enriched (>98%) subsets of human ?-and ?-cells were obtained by flow cytometric sorting after intracellular staining with c-peptide and glucagon antibody. The method of sorting based on intracellular staining is possible because miRNAs are stable after fixation. MiRNA expression levels were determined by quantitative high throughput PCR-based miRNA array platform screening. Most of the miRNAs were preferentially expressed in ?-cells. From the total of 667 miRNAs screened, the Significant Analysis of Microarray identified 141 miRNAs, of which only 7 were expressed more in ?-cells (?-miRNAs) and 134 were expressed more in ?-cells (?-miRNAs). Bioinformatic analysis identified potential targets of ?-miRNAs analyzing the Beta Cell Gene Atlas, described in the T1Dbase, the web platform, supporting the type 1 diabetes (T1D) community. cMaf, a transcription factor regulating glucagon expression expressed selectively in ?-cells (TF?) is targeted by ?-miRNAs; miR-200c, miR-125b and miR-182. Min6 cells treated with inhibitors of these miRNAs show an increased expression of cMaf RNA. Conversely, over expression of miR-200c, miR-125b or miR-182 in the mouse alpha cell line ?TC6 decreases the level of cMAF mRNA and protein. MiR-200c also inhibits the expression of Zfpm2, a TF? that inhibits the PI3K signaling pathway, at both RNA and protein levels.In conclusion, we identified miRNAs differentially expressed in pancreatic ?- and ?-cells and their potential transcription factor targets that could add new insights into different aspects of islet biology and pathophysiology.

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Human islets contain four distinct subtypes of ? cells.

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Human islets contain four distinct subtypes of β cells.

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