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11β‐HSD1 Mediates Insulin Resistance and Type 2 Diabetes Mellitus through JNK Activation
Author(s) -
Peng Kesong,
Liang Guang
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.575.1
Subject(s) - insulin resistance , medicine , endocrinology , type 2 diabetes mellitus , diabetes mellitus , insulin , type 2 diabetes , 11β hydroxysteroid dehydrogenase type 1 , stimulation , biology , enzyme , dehydrogenase , biochemistry
Background Obesity‐induced insulin resistance is the major determinant of metabolic syndrome, which precedes the development of type 2 diabetes mellitus.11β‐Hydroxysteroid dehydrogenase type 1 (11β‐HSD1) is considered a potential therapeutic target in the treatment of type 2 diabetes mellitus, while the potential mechanism is not very clearly identified. Methods In vitro cultured 3T3‐L1 pre‐adipocytes, prednisone and over‐expressed 11β‐HSD1 were used to induce insulin resistance. Type 2 diabetes mellitus mouse models were treated with 11β‐HSD1 inhibitor PF00195715 and JNK inhibitor C66 by gavage, respectively. Results Stimulation of prednisone or over‐expressed 11β‐HSD1 significantly disturbed insulin signal pathway, decreased AKT phosphorylation and led to insulin resistance, while these effects were reversed by PF00195715 and C66. Either C66 or DN‐JNK significantly attenuated the 11β‐HSD1 over‐expression induced insulin resistance, indicating a mediated role of JNK. Oral administration with either PF00195715 or C66 in mouse models remarkably relieved insulin resistance and type 2 diabetes mellitus. Conclusion 11β‐HSD1 mediates insulin resistance and type 2 diabetes mellitus through JNK activation.