Insulin granule morphology and crinosome formation in mice lacking the pancreatic β cell-specific phogrin (PTPRN2) gene

Yasui, Tadashi; Mashiko, Mutsumi; Obi, Akihiro; Mori, Hiroyuki; Ito-Murata, Moeko; Hayakawa, Hiroki; Kikuchi, Shota; Hosaka, Masahiro; Kubota, Chisato; Torii, Seiji; Gomi, Hiroshi

doi:10.1007/s00418-023-02256-8

Cited by 3 publications

(3 citation statements)

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“…Recently, we constructed a mouse model by specifically deleting the phogrin gene in pancreatic β-cells, through a traditional Cre/LoxP conditional knockout system expressing the Cre recombinase driven by the rat insulin promoter, RIP , and showed that insulin content in βKO (RIP-Cre +/− Phogrin flox/flox , βKO) islets was slightly less than that in control (RIP-Cre +/− Phogrin +/+ , Ctrl) islets [ 8 , 29 ]. This was due to a slight decrease in insulin granule density, as observed via electron microscopy [ 29 ]. However, blood insulin levels and insulin secretion from isolated islets upon high glucose stimulation were unaffected by phogrin deletion, whereas basal insulin release was slightly upregulated in βKO islets ( Supplementary Figure S1 ).…”

Section: Resultsmentioning

confidence: 99%

“…The anti-phogrin and IA-2 rabbit antibodies and the murine monoclonal antibody against phogrin (C38-2) have been previously characterized [ 19 , 29 ]. C38-2 recognizes the luminal (extracellular) matN region of phogrin protein structure encompassing amino acids 414 to 599.…”

Section: Methodsmentioning

confidence: 99%

“…The mice were anesthetized by intraperitoneally injecting 0.1 mg/g/bw sodium pentobarbital and then processed for immunohistochemical analyses [ 29 ]. Removed pancreases were fixed in 4% paraformaldehyde in 0.1 M phosphate buffer (pH 7.4) and embedded in paraffin.…”

Section: Methodsmentioning

confidence: 99%

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Phogrin Regulates High-Fat Diet-Induced Compensatory Pancreatic β-Cell Growth by Switching Binding Partners

Kubota,

Torii,

Hosaka

et al. 2024

Nutrients

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The receptor protein tyrosine phosphatase phogrin primarily localizes to hormone secretory granules in neuroendocrine cells. Concurrent with glucose-stimulated insulin secretion, phogrin translocates to pancreatic β-cell plasma membranes, where it interacts with insulin receptors (IRs) to stabilize insulin receptor substrate 2 (IRS2) that, in turn, contributes to glucose-responsive β-cell growth. Pancreatic β-cell development was not altered in β-cell-specific, phogrin-deficient mice, but the thymidine incorporation rate decreased in phogrin-deficient islets with a moderate reduction in IRS2 protein expression. In this study, we analyzed the β-cell response to high-fat diet stress and found that the compensatory expansion in β-cell mass was significantly suppressed in phogrin-deficient mice. Phogrin–IR interactions occurred only in high-fat diet murine islets and proliferating β-cell lines, whereas they were inhibited by the intercellular binding of surface phogrin under confluent cell culture conditions. Thus, phogrin could regulate glucose-stimulated compensatory β-cell growth by changing its binding partner from another β-cell phogrin to IR in the same β-cells.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Phogrin Regulates High-Fat Diet-Induced Compensatory Pancreatic β-Cell Growth by Switching Binding Partners

Kubota,

Torii,

Hosaka

et al. 2024

Nutrients

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In focus in HCB

Taatjes,

Roth

2024

Histochem Cell Biol

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Protein Tyrosine Phosphatase Receptors N and N2 Control Pituitary Melanotroph Development and POMC Expression

Constantin,

Sokanovic,

Mochimaru

et al. 2024

Endocrinology

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The neuroendocrine marker genes Ptprn and Ptprn2 encode protein tyrosine phosphatase receptors N and N2, two members of protein tyrosine phosphatase receptors void of enzymatic activity, and whose function and mechanism of action have not been elucidated. To explore the role(s) of Ptprn and Ptprn2 on the hypothalamic-pituitary-adrenal axis, we used mice in which both genes were knocked out (DKO). The focus in study was on corticotrophs and melanotrophs from the anterior and intermediate lobes of the pituitary gland, respectively. In both sexes, DKO caused an increase in the expression of the corticotroph/melanotroph genes Pomc and Tbx19 and the melanotroph-specific gene Pax7. We also found in vivo and in vitro increased synthesis and release of beta-endorphin, alpha-MSH, and ACTH in DKO mice, which was associated with increased serum corticosterone levels and adrenal mass. DKO also increased the expression of other melanotroph-specific genes, but not corticotroph-specific genes. The dopaminergic pathway in the hypothalamus and dopaminergic receptors in melanotrophs were not affected in DKO mice. However, hyperplasia of the intermediate lobe was observed in DKO females and males, accompanied by increased POMC immunoreactivity per cell. These results indicate that PTPRNs contribute to hypothalamic-pituitary-adrenal function by being involved in processes governing postnatal melanotroph development and Pomc expression.

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Insulin granule morphology and crinosome formation in mice lacking the pancreatic β cell-specific phogrin (PTPRN2) gene

Cited by 3 publications

References 65 publications

Phogrin Regulates High-Fat Diet-Induced Compensatory Pancreatic β-Cell Growth by Switching Binding Partners

Phogrin Regulates High-Fat Diet-Induced Compensatory Pancreatic β-Cell Growth by Switching Binding Partners

In focus in HCB

Protein Tyrosine Phosphatase Receptors N and N2 Control Pituitary Melanotroph Development and POMC Expression

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