The hydrolase DDAH2 enhances pancreatic insulin secretion by transcriptional regulation of secretagogin through a Sirt1‐dependent mechanism in mice

Hara, Kazuhiro; Wakino, Shu; Kimoto, Masumi; Minakuchi, Hitoshi; Fujimura, Keiko; Hosoya, Koji; Komatsu, Motoaki; Kaneko, Yuka; Kanda, Takeshi; Tokuyama, Hirobumi; Hayashi, Kôichi; Itoh, Hiroshi

doi:10.1096/fj.12-226092

Cited by 38 publications

(42 citation statements)

References 47 publications

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“…Transfection of an intact islet is difficult even with viral vector, while dissociated cells are more susceptible for gene transfection. With the HS system, genes can be delivered to nuclei of ICs or MSCs to improve cell functions 43,44 before the spheroid formation, which can make highly functionalized cell clusters for the treatment of type 1 diabetes.…”

Section: Discussionmentioning

confidence: 99%

Transplantation of Heterospheroids of Islet Cells and Mesenchymal Stem Cells for Effective Angiogenesis and Antiapoptosis

Shin

Jeong

Han

et al. 2015

Tissue Engineering Part A

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Although islet transplantation has been suggested as an alternative therapy for type 1 diabetes, there are efficiency concerns that are attributed to poor engraftment of transplanted islets. Hypoxic condition and delayed vasculogenesis induce necrosis and apoptosis of the transplanted islets. To overcome these limitations in islet transplantation, heterospheroids (HSs), which consist of rat islet cells (ICs) and human bone marrow-derived mesenchymal stem cells (hMSCs), were transplanted to the kidney and liver. The HSs cultured under the hypoxic condition system exhibited a significant increase in antiapoptotic gene expression in ICs. hMSCs in the HSs secreted angiogenic and antiapoptotic proteins. With the HS system, ICs and hMSCs were successfully located in the same area of the liver after transplantation of HSs through the portal vein, whereas the transplantation of islets and the dissociated hMSCs did not result in localization of transplanted ICs and hMSCs in the same area. HS transplantation resulted in an increase in angiogenesis at the transplantation area and a decrease in the apoptosis of transplanted ICs after transplantation into the kidney subcapsule compared with transplantation of islet cell clusters (ICCs). Insulin production levels of ICs were higher in the HS transplantation group compared with the ICC transplantation group. The HS system may be a more efficient transplantation method than the conventional methods for the treatment of type 1 diabetes.

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Section: Discussionmentioning

confidence: 99%

Transplantation of Heterospheroids of Islet Cells and Mesenchymal Stem Cells for Effective Angiogenesis and Antiapoptosis

Shin

Jeong

Han

et al. 2015

Tissue Engineering Part A

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“…We hypothesize that these cells may contact the ventricular surface with their processes or serve as a site for adult neurogenesis. Whilst at this point either argument is speculative, they are conceivable since, firstly, secretagogin has been shown (i) to be involved in both release mechanisms Hasegawa et al, 2013] and (ii) the adult olfactory proliferation and migration system [Mulder et al, 2009], respectively. Secondly, secretagogin + neurons line along cell-free laminae that separate brain regions with different pallial or subpallial origins.…”

Section: Hot Spots: Secretagoginmentioning

confidence: 99%

“…Here, we show that the supraoptic nucleus (nucleus decussationis supraopticae, pars ventralis) is densely packed with secretagogin + neurons with further cell groups present in the lateral hypothalamus, and paraventricular and infundibular nuclei. Since secretagogin was shown to impact vesicle secretion and release Bauer et al, 2011;Hasegawa et al, 2013], it is conceivable that secretagogin plays a role in the control of hypothalamic hormone secretion/release.…”

Section: + -Binding Proteinsmentioning

confidence: 99%

“…Given its relatively low Ca 2+ -binding affinity and conformational modifications upon Ca 2+ binding, secretagogin qualifies as a Ca 2+ sensor [Rogstam et al, 2007]. The predicted interactome of secretagogin includes members of SNARE (soluble NSF attachment protein receptor) superfamily of proteins, suggesting its involvement in regulating secretory and synaptic vesicle trafficking and activity-dependent release [Rogstam et al, 2007;Bauer et al, 2011;Hasegawa et al, 2013]. Secretagogin is expressed in essentially all organ systems [Wagner et al, 2000;Alpár et al, 2012].…”

Section: Introductionmentioning

confidence: 99%

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Revival of Calcium-Binding Proteins for Neuromorphology: Secretagogin Typifies Distinct Cell Populations in the Avian Brain

Gáti

Lendvai

Hökfelt³

et al. 2014

Brain Behav Evol

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In the vertebrate nervous system, the Ca²⁺-binding proteins parvalbumin, calbindin and calretinin have been extensively used to elaborate the molecular diversity of neuronal subtypes. Secretagogin is a phylogenetically conserved Ca²⁺-binding protein, which marks neuronal populations largely distinct from other Ca²⁺-binding proteins in mammals. Whether secretagogin is expressed in nonmammalian vertebrates, particularly in birds, and, if so, with a brain cytoarchitectonic design different from that of mammals is unknown. Here, we show that secretagogin is already present in the hatchlings' brain with continued presence into adulthood. Secretagogin-immunoreactive neurons primarily accumulate in the olfactory bulb, septum, subpallial amygdala, hippocampus, hypothalamus, habenular nuclei and deep layers of the optic tectum of adult domestic chicks (Gallus domesticus). In the olfactory bulb, secretagogin labels periglomerular neurons as well as a cell continuum ascending dorsomedially, reaching the ventricular wall. Between the hippocampus and septal nuclei, the interconnecting thin septal tissue harbors secretagogin-immunoreactive neurons that contact the ventricular wall with their ramifying dendritic processes. Secretagogin is also present in the neuroendocrine hypothalamus, with particularly rich neuronal clusters seen in its suprachiasmatic and infundibular nuclei. Secretagogin expression identified a hitherto undescribed cell contingent along intratelencephalic cell-free laminae separating brain regions or marking the palliosubpallial boundary, as well as a dense neuronal population in the area corticoidea lateralis. In both the telencephalon and midbrain, secretagogin complemented the distribution of the canonical ‘neuronal' Ca²⁺-binding proteins. Our findings identify novel neuronal subtypes, connectivity patterns in brain areas functionally relevant to olfaction, orientation, behavior as well as endocrine functions, which will help refine existing concepts on the neuronal diversity and organizational principles of the avian brain.

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“…Thus, the elevation of ADMA due to the decreased DDAH2 may result in a decrease in NO production by cNOS, thereby impairing the insulinotropic and antiapoptotic effects of low-concentration NO. DDAH2 has also been suggested to NO-independently increase GSIS by increasing the transcription of secretagogin, an insulin vesicle docking protein (47).…”

Section: No In Type 2 Dmmentioning

confidence: 99%

Dual Role of Nitric Oxide in Pancreatic β-Cells

Kaneko

Ishikawa

2013

J Pharmacol Sci

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Abstract. An involvement of inducible nitric oxide (NO) synthase (NOS) in pancreatic b-cell degeneration during the process of type 1 diabetes has been well discussed. Recently, there is growing evidence for pivotal roles of constitutive NOS (cNOS) in b-cells; the presence of NOS1 and NOS3 in pancreatic b-cells and the effects of low-concentration NO, which is assumed to be derived from cNOS, on b-cell functions have been reported. However, the roles of cNOS-derived NO in b-cells are still under debate. One of the reasons seems to be that NO has multiple biological activities, which are dependent on its concentration. In b-cells, NO has been shown to exert positive and negative regulation of insulin secretion and anti-and pro-apoptotic activities, which is likely to be dependent on concentrations. In this review article, we will describe the current understanding of the roles of NO in pancreatic b-cells, especially focusing on cNOS-derived NO and its differential roles depending on concentrations.

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The hydrolase DDAH2 enhances pancreatic insulin secretion by transcriptional regulation of secretagogin through a Sirt1‐dependent mechanism in mice

Cited by 38 publications

References 47 publications

Transplantation of Heterospheroids of Islet Cells and Mesenchymal Stem Cells for Effective Angiogenesis and Antiapoptosis

Transplantation of Heterospheroids of Islet Cells and Mesenchymal Stem Cells for Effective Angiogenesis and Antiapoptosis

Revival of Calcium-Binding Proteins for Neuromorphology: Secretagogin Typifies Distinct Cell Populations in the Avian Brain

Dual Role of Nitric Oxide in Pancreatic β-Cells

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