Characterization of the Secretome, Transcriptome, and Proteome of Human β Cell Line EndoC-βH1

Ryaboshapkina, Maria; Saitoski, Kevin; Hamza, Ghaith M.; Jarnuczak, Andrew F.; Pechberty, Sèverine; Berthault, Claire; Sengupta, Kaushik; Underwood, Christina Rye; Andersson, Shalini; Scharfmann, Raphaël

doi:10.1016/j.mcpro.2022.100229

Cited by 7 publications

(5 citation statements)

References 84 publications

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“…1 H ). Omics data analysis confirmed that EndoC-βH1 cells are a representative in vitro model for human beta cells ( 35 ). Thus, mouse and human beta cells express PCSK9, and EndoC-βH1 cells can be used as a model to study PCSK9 regulation and function in human beta cells.…”

Section: Resultsmentioning

confidence: 84%

“…Acquisition of proteomics and RNA-Seq data and sample size calculation for omics experiments have been previously described ( 35 ). Benjamini–Yekutieli method ( 60 ) was used to adjust for multiple testing for ingenuity pathway analysis terms because of nonignorable overlap between genes underlying top pathways.…”

Section: Methodsmentioning

confidence: 99%

“…The datasets generated during and/or analyzed during the current study were previously published ( 35 ) and are available from the corresponding authors.…”

Section: Data Availabilitymentioning

confidence: 99%

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Proprotein convertase PCSK9 affects expression of key surface proteins in human pancreatic beta cells via intracellular and extracellular regulatory circuits

Saitoski¹,

Ryaboshapkina²,

Hamza³

et al. 2022

Journal of Biological Chemistry

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Section: Resultsmentioning

confidence: 84%

Section: Methodsmentioning

confidence: 99%

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Proprotein convertase PCSK9 affects expression of key surface proteins in human pancreatic beta cells via intracellular and extracellular regulatory circuits

Saitoski¹,

Ryaboshapkina²,

Hamza³

et al. 2022

Journal of Biological Chemistry

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“…The effect of succinate as an extracellular insulin secretagogue was confirmed in EndoC-βH5 cells which, compared with other commonly used human β-cell lines, do not present limitations regarding the expression of some GPCRs (i.e., GLP1-R) (50,51). EndoC-βH5 cells showed an increase in insulin secretion when SUCNR1 was activated by both extracellular succinate or cESA under conditions of no glucose (1.5-fold or 1.3-fold increase, respectively) and highglucose (1.4-fold increase for both) conditions (Figure 3E).…”

Section: β-Cells Sense Extracellular Succinate and Release Insulin In...mentioning

confidence: 82%

SUCNR1 regulates insulin secretion and glucose elevates the succinate response in people with prediabetes

Sabadell-Basallote,

Astiarraga,

Castaño

et al. 2024

Journal of Clinical Investigation

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Pancreatic β cell dysfunction is a key feature of type 2 diabetes, and novel regulators of insulin secretion are desirable. Here, we report that succinate receptor 1 (SUCNR1) is expressed in β cells and is upregulated in hyperglycemic states in mice and humans. We found that succinate acted as a hormone-like metabolite and stimulated insulin secretion via a SUCNR1-Gq-PKC–dependent mechanism in human β cells. Mice with β cell–specific Sucnr1 deficiency exhibited impaired glucose tolerance and insulin secretion on a high-fat diet, indicating that SUCNR1 is essential for preserving insulin secretion in diet-induced insulin resistance. Patients with impaired glucose tolerance showed an enhanced nutrition-related succinate response, which correlates with the potentiation of insulin secretion during intravenous glucose administration. These data demonstrate that the succinate/SUCNR1 axis is activated by high glucose and identify a GPCR-mediated amplifying pathway for insulin secretion relevant to the hyperinsulinemia of prediabetic states.

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“…43,44 In addition, senescent β cells have been reported to secrete senescence-associated secretory phenotypes that are rich in EVs and cause dysfunction of adjacent cells through paracrine effects. 45 The reported anatomical characteristics of an IAA permits the access of high concentrations of islet-derived miR-503-322 to exocrine cells. Indeed, a recent study has determined that islet CCK can promote Kras-driven PDAC development of an endocrine exchange signal other than insulin, 11 supporting the existence of endocrine-exocrine crosstalk via IAA.…”

Section: Discussionmentioning

confidence: 99%

Endocrine-exocrine miR-503-322 drives aging-associated pancreatitis via targeting MKNK1 in acinar cells

Zhu,

Liu,

et al. 2024

Preprint

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Aging is the major risk factor for chronic pancreatitis and severity determinant for its acute attack, yet the underlying cause is unclear. Here, we demonstrate that senescent β-cells of endocrine pancreas decide the onset and severity of chronic and acute pancreatitis. During physiological aging, senescent β-cells increase the expression of miR-503-322 which is secreted as nano-vesicles to enter exocrine acinar cells, driving a causal and reversible role on aging-associated pancreatitis. Mechanistically, miR-503-322 represses MKNK1 to inhibit acinar-cell secretion and proliferation, thereby causing autodigestion and repairing damage of exocrine pancreas. In the elderly population, serum miR-503 concentration is negatively correlated with amylase, prone to chronic pancreatitis due to increased miR-503 and decreased MKNK1 in the elderly pancreas. Our findings highlight the miR-503-322–MKNK1 axis mediating the endocrine-exocrine regulatory pathway specifically in aged mice and humans. Modulating this axis may provide potential preventive and therapeutic strategies for aging-associated pancreatitis.

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Characterization of the Secretome, Transcriptome, and Proteome of Human β Cell Line EndoC-βH1

Cited by 7 publications

References 84 publications

Proprotein convertase PCSK9 affects expression of key surface proteins in human pancreatic beta cells via intracellular and extracellular regulatory circuits

Proprotein convertase PCSK9 affects expression of key surface proteins in human pancreatic beta cells via intracellular and extracellular regulatory circuits

SUCNR1 regulates insulin secretion and glucose elevates the succinate response in people with prediabetes

Endocrine-exocrine miR-503-322 drives aging-associated pancreatitis via targeting MKNK1 in acinar cells

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