Intra-Islet PACAP Protects Pancreatic β-Cells Against Glucotoxicity and Lipotoxicity

Nakata, Masao; Shintani, Norihito; Hashimoto, Hitoshi; Baba, Akemichi; Yada, Toshihiko

doi:10.1007/s12031-010-9383-4

Cited by 26 publications

(15 citation statements)

References 36 publications

(30 reference statements)

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“…In the study from Nakata, short-term treatment of islets with palmitate was performed and it was found that the treatment markedly impaired both [Ca 2 + ]i and GSIS in islets of PACAPnull, but not wild-type mice (Nakata et al, 2010). These results indicated that endogenous PACAP in islets played an important role in protecting beta cells against lipotoxicity.…”

Section: Silent Information Regulator 2 Proteinmentioning

confidence: 97%

Signaling Molecules Involved in Lipid-Induced Pancreatic Beta-Cell Dysfunction

Shao

Yang

Yuan

et al. 2013

DNA and Cell Biology

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The increasing incidence of type 2 diabetes mellitus is partially due to the rising obesity rates and the elevated levels of free fatty acids (FFAs). It is known that FFAs are putative mediators of beta-cell dysfunction, which is characterized with impaired glucose-stimulated insulin secretion and increased apoptosis, being defined as lipotoxicity. To date, many factors and their related signal pathways have been reported to be involved in FFAinduced beta-cell dysfunction. However, the entire blueprint is still not obtained. Some essential and newfound effectors, including the sterol regulatory element-binding protein (SREBP)-1c, farnesoid X receptor (FXR), forkhead box-containing protein O (FoxO) 1, ubiquitin C-terminal hydrolase L (UCHL) 1, N-myc downstreamregulated gene (NDRG) 2, perilipin family proteins, silent information regulator 2 protein 1 (Sirt1), pituitary adenylate cyclase-activating polypeptide (PACAP), and ghrelin are described in this review, which may help to further understand the molecular network for lipotoxicity.

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Section: Silent Information Regulator 2 Proteinmentioning

confidence: 97%

Signaling Molecules Involved in Lipid-Induced Pancreatic Beta-Cell Dysfunction

Shao

Yang

Yuan

et al. 2013

DNA and Cell Biology

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“…Betatrophin mRNA expressions in the liver, WAT and BAT were measured by real-time PCR [17]. Total RNA was isolated using TRIzol (Invitrogen, Carlsbad, CA, USA) and treated with RQ1-DNase (Promega, Madison, WI, USA).…”

Section: Rna Preparation and Real-time Rt-pcr Analysismentioning

confidence: 99%

Betatrophin expression is promoted in obese hyperinsulinemic type 2 but not type 1 diabetic mice

Nakata

Shinozaki

et al. 2016

Endocr J

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“…Furthermore, PACAP has also been shown to exert trophic effects on pancreatic ␤-cells (36,37) as in other neuroendocrine cells such as chromaffin cells (38), an effect that may involve SelT. In fact, it has been reported that islets of PACAP-knockout mice are more sensitive to lipo-and glucotoxicity (39). It is thus tempting to speculate that PACAP may protect ␤-cells via SelT up-regulation, which could reduce reactive oxygen species levels and glucotoxicity.…”

Section: Ko Wtmentioning

confidence: 99%

The PACAP-Regulated Gene Selenoprotein T Is Abundantly Expressed in Mouse and Human β-Cells and Its Targeted Inactivation Impairs Glucose Tolerance

et al. 2013

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Selenoproteins are involved in the regulation of redox status, which affects several cellular processes, including cell survival and homeostasis. Considerable interest has arisen recently concerning the role of selenoproteins in the regulation of glucose metabolism. Here, we found that selenoprotein T (SelT), a new thioredoxin-like protein of the endoplasmic reticulum, is present at high levels in human and mouse pancreas as revealed by immunofluorescence and quantitative PCR. Confocal immunohistochemistry studies revealed that SelT is mostly confined to insulin- and somatostatin-producing cells in mouse and human islets. To elucidate the role of SelT in β-cells, we generated, using a Cre-Lox strategy, a conditional pancreatic β-cell SelT-knockout C57BL/6J mice (SelT-insKO) in which SelT gene disruption is under the control of the rat insulin promoter Cre gene. Glucose administration revealed that male SelT-insKO mice display impaired glucose tolerance. Although insulin sensitivity was not modified in the mutant mice, the ratio of glucose to insulin was significantly higher in the SelT-insKO mice compared with wild-type littermates, pointing to a deficit in insulin production/secretion in mutant mice. In addition, morphometric analysis showed that islets from SelT-insKO mice were smaller and that their number was significantly increased compared with islets from their wild-type littermates. Finally, we found that SelT is up-regulated by pituitary adenylate cyclase-activating polypeptide (PACAP) in β-pancreatic cells and that SelT could act by facilitating a feed-forward mechanism to potentiate insulin secretion induced by the neuropeptide. Our findings are the first to show that the PACAP-regulated SelT is localized in pancreatic β- and δ-cells and is involved in the control of glucose homeostasis.

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Intra-Islet PACAP Protects Pancreatic β-Cells Against Glucotoxicity and Lipotoxicity

Cited by 26 publications

References 36 publications

Signaling Molecules Involved in Lipid-Induced Pancreatic Beta-Cell Dysfunction

Signaling Molecules Involved in Lipid-Induced Pancreatic Beta-Cell Dysfunction

Betatrophin expression is promoted in obese hyperinsulinemic type 2 but not type 1 diabetic mice

The PACAP-Regulated Gene Selenoprotein T Is Abundantly Expressed in Mouse and Human β-Cells and Its Targeted Inactivation Impairs Glucose Tolerance

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