Efficient gene transfer into murine pancreatic islets using adenovirus vectors

Mukai, Eri; Fujimoto, Shimpei; Sakurai, Fuminori; Kono, Kenji; Yamashita, Manabu; Inagaki, Nobuya; Mizuguchi, Hiroyuki

doi:10.1016/j.jconrel.2007.01.012

Cited by 16 publications

(17 citation statements)

References 33 publications

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“…Wistar rats were subjected to laparotomy under general anesthesia. After ligation of the portal vein, the superior aorta, and the hepatic, mesenteric, and right and left renal arteries, adenoviruses (4 × 10 10 pfu/pancreas) encoding luciferase (Luc), wild type hPASK (WT), or hPASK mutants (G1117E and L1051V) were injected in the celiac trunk of the inferior aorta as previously described (8, 29). Rat islets of Langerhans were isolated as described (8), pre-cultured for 16 h at 2.8 mmol/liter glucose, and then exposed for 24 h to 2.8 or 16.7 mmol/liter of glucose.…”

Section: Methodsmentioning

confidence: 99%

Human Mutation within Per-Arnt-Sim (PAS) Domain-containing Protein Kinase (PASK) Causes Basal Insulin Hypersecretion

Semplici

Vaxillaire

Fogarty

et al. 2011

Journal of Biological Chemistry

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Background: The glucose sensor PAS kinase (PASK) plays a fundamental role in pancreatic islet physiology.Results: A single amino acid substitution in the human PASK kinase domain stimulates enzyme activity and increases insulin secretion at low glucose.Conclusion: A rare, naturally occurring mutation in PASK modulates insulin release in man.Significance: We provide direct genetic evidence for a role for PASK in controlling insulin secretion in man.

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Section: Methodsmentioning

confidence: 99%

Human Mutation within Per-Arnt-Sim (PAS) Domain-containing Protein Kinase (PASK) Causes Basal Insulin Hypersecretion

Semplici

Vaxillaire

Fogarty

et al. 2011

Journal of Biological Chemistry

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“…For arterial delivery of adenoviral vectors in rat pancreas, Wistar rats were anesthetized and subjected to laparotomy. After ligation of the portal vein, the superior aorta, and the hepatic, mesenteric, and right and left renal arteries, adenoviruses (4.10 10 pfu/pancreas) were injected in the celiac trunk of the inferior aorta as described (19). …”

Section: Methodsmentioning

confidence: 99%

Involvement of Per-Arnt-Sim Kinase and Extracellular-Regulated Kinases-1/2 in Palmitate Inhibition of Insulin Gene Expression in Pancreatic β-Cells

et al. 2009

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OBJECTIVEProlonged exposure of pancreatic β-cells to simultaneously elevated levels of fatty acids and glucose (glucolipotoxicity) impairs insulin gene transcription. However, the intracellular signaling pathways mediating these effects are mostly unknown. This study aimed to ascertain the role of extracellular-regulated kinases (ERKs)1/2, protein kinase B (PKB), and Per-Arnt-Sim kinase (PASK) in palmitate inhibition of insulin gene expression in pancreatic β-cells.RESEARCH DESIGN AND METHODSMIN6 cells and isolated rat islets were cultured in the presence of elevated glucose, with or without palmitate or ceramide. ERK1/2 phosphorylation, PKB phosphorylation, and PASK expression were examined by immunoblotting and real-time PCR. The role of these kinases in insulin gene expression was assessed using pharmacological and molecular approaches.RESULTSExposure of MIN6 cells and islets to elevated glucose induced ERK1/2 and PKB phosphorylation, which was further enhanced by palmitate. Inhibition of ERK1/2, but not of PKB, partially prevented the inhibition of insulin gene expression in the presence of palmitate or ceramide. Glucose-induced expression of PASK mRNA and protein levels was reduced in the presence of palmitate. Overexpression of wild-type PASK increased insulin and pancreatic duodenal homeobox-1 gene expression in MIN6 cells and rat islets incubated with glucose and palmitate, whereas overexpression of a kinase-dead PASK mutant in rat islets decreased expression of insulin and pancreatic duodenal homeobox-1 and increased C/EBPβ expression.CONCLUSIONSBoth the PASK and ERK1/2 signaling pathways mediate palmitate inhibition of insulin gene expression. These findings identify PASK as a novel mediator of glucolipotoxicity on the insulin gene in pancreatic β-cells.

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“…However, neither AVs nor AAVs infect the pancreas selectively; indeed, both viruses display broad tissue tropism, with the liver being their prime target organ (44). This has necessitated the use of invasive procedures such as injection of the vector directly into the pancreas (44) or into the left gastric artery (32) to enhance delivery to the desired target cells. While expression of the incorporated gene can be restricted to beta cells using the insulin promoter (36), infection of other susceptible cells occurs with potentially adverse effects (38,47).…”

Section: Discussionmentioning

confidence: 99%

A Novel Pancreatropic Coxsackievirus Vector Expressing Glucagon-Like Peptide 1 Reduces Hyperglycemia in Streptozotocin-Treated Mice

Dan

Chantler

2011

J Virol

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A coxsackievirus vector, vCVB(dm) (v stands for vector, CVB stands for group B coxsackievirus, and dm stands for double mutant), has been produced from a unique strain of coxsackievirus B3 (CVB3) containing 2 mutations that confer the property of highly selective pancreatropism. This vector has been tested as a delivery vehicle for glucagon-like peptide 1 (GLP-1), a peptide that enhances pancreatic regeneration following tissue damage. vCVB(dm) is a live vector comprising the entire plus-strand RNA genome with a multiple cloning site (MCS) inserted between the P1 and P2 gene regions. The MCS is flanked by sequences encoding the cleavage site for viral protease 2Apro that processes the polyprotein to release the incorporated gene. Our studies show that this vector selectively delivers GLP-1 to the pancreas where it is expressed in foci scattered throughout the acinar tissue for 4 or 5 days. Moreover, expression is associated with new beta cell clusters in juxtaposition to vector-infected cells. Inoculation of streptozotocin (STZ)-treated mice with vCVB(dm)GLP-1 was found to suppress development of hyperglycemia and increase insulin production relative to mice treated with STZ alone or with empty vector. This vector has the advantage of exclusively targeting pancreas and has potential use for short-term gene delivery to this tissue. The lack of viral integration provides a significant safety feature, making this vector a possible option for use as a therapeutic tool for pancreas-related diseases, including type 1 and 2 diabetes, pancreatitis, and pancreatic cancer.

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Efficient gene transfer into murine pancreatic islets using adenovirus vectors

Cited by 16 publications

References 33 publications

Human Mutation within Per-Arnt-Sim (PAS) Domain-containing Protein Kinase (PASK) Causes Basal Insulin Hypersecretion

Human Mutation within Per-Arnt-Sim (PAS) Domain-containing Protein Kinase (PASK) Causes Basal Insulin Hypersecretion

Involvement of Per-Arnt-Sim Kinase and Extracellular-Regulated Kinases-1/2 in Palmitate Inhibition of Insulin Gene Expression in Pancreatic β-Cells

A Novel Pancreatropic Coxsackievirus Vector Expressing Glucagon-Like Peptide 1 Reduces Hyperglycemia in Streptozotocin-Treated Mice

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