Abstract
A major feature of type 1 diabetes mellitus (T1DM) is hyperglycemia and dysfunction of pancreatic β-cells. In a previous study, we have shown that Tat-DJ-1 protein inhibits pancreatic RINm5F β-cell death caused by oxidative stress. In this study, we examined effects of Tat-DJ-1 protein on streptozotocin (STZ)-induced diabetic mice. Wild type (WT) Tat-DJ-1 protein transduced into pancreas where it markedly inhibited pancreatic β-cell destruction and regulated levels of serum parameters including insulin, alkaline phosphatase (ALP), and free fatty acid (FFA) secretion. In addition, transduced WT Tat-DJ-1 protein significantly inhibited the activation of NF-κB and MAPK (ERK and p38) expression as well as expression of COX-2 and iNOS in STZ exposed pancreas. In contrast, treatment with C106A mutant Tat-DJ-1 protein showed no protective effects. Collectively, our results indicate that WT Tat-DJ-1 protein can significantly ameliorate pancreatic tissues in STZ-induced diabetes in mice. [BMB Reports 2018; 51(7): 362-367].
MeSH terms
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Alkaline Phosphatase / blood
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Animals
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Cyclooxygenase 2 / metabolism
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Diabetes Mellitus, Experimental / chemically induced
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Diabetes Mellitus, Experimental / drug therapy*
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Diabetes Mellitus, Experimental / pathology
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Fatty Acids, Nonesterified / blood
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Gene Products, tat / genetics*
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Insulin / blood
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Insulin-Secreting Cells / cytology
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Insulin-Secreting Cells / metabolism
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Male
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Mice
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Mice, Inbred ICR
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NF-kappa B / metabolism
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Nitric Oxide Synthase Type II / metabolism
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Oxidative Stress / drug effects
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Pancreas / metabolism
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Protective Agents / pharmacology
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Protective Agents / therapeutic use*
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Protein Deglycase DJ-1 / genetics*
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / pharmacology
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Recombinant Fusion Proteins / therapeutic use*
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Fatty Acids, Nonesterified
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Gene Products, tat
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Insulin
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NF-kappa B
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Protective Agents
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Recombinant Fusion Proteins
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Nitric Oxide Synthase Type II
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Cyclooxygenase 2
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Extracellular Signal-Regulated MAP Kinases
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p38 Mitogen-Activated Protein Kinases
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Protein Deglycase DJ-1
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Alkaline Phosphatase