Prolonged elevation of glucose can adversely affect β-cell function. Oxidative stress, which has been implicated in glucose-induced β-cell dysfunction, can activate c-jun N-terminal kinase (JNK). However, whether JNK is causal in glucose-induced β-cell dysfunction in vivo is unclear. Therefore, we aimed at investigating the causal role of JNK activation in in vivo models of glucose-induced β-cell dysfunction. Glucose-induced β-cell dysfunction was investigated in the presence or absence of JNK inhibition. JNK inhibition was achieved using either (i) the JNK-specific inhibitor SP600125 or (ii) JNK-1-null mice. (i) Rats or mice were infused intravenously with saline or glucose with or without SP600125. (ii) JNK-1 null mice and their littermate wild-type controls were infused intravenously with saline or glucose. Following the glucose infusion periods in rats and mice, β-cell function was assessed in isolated islets or in vivo using hyperglycemic clamps. Forty-eight-hour hyperglycemia at ~20 mM in rats or 96-hour hyperglycemia at ~13 mM in mice impaired β-cell function in isolated islets and in vivo. Inhibition of JNK using either SP600125 or JNK-1-null mice prevented glucose-induced β-cell dysfunction in isolated islets and in vivo. Islets of JNK-1-null mice exposed to hyperglycemia in vivo showed an increase in Pdx-1 and insulin 2 mRNA, whereas islets of wild-type mice did not. Together, these data show that JNK pathway is involved in glucose-induced β-cell dysfunction in vivo and is thus a potential therapeutic target for type 2 diabetes.
Pubmed ID: 30215691 RIS Download
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This monoclonal targets JUND
View all literature mentionsThis polyclonal targets ACTG1, ACTC1, ACTA1, ACTA2, ACTG2, ACTB
View all literature mentionsThis unknown targets c-Jun, phospho (Ser73)
View all literature mentionsThis monoclonal targets JUND
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