David A Bulger1, Jermaine Conley2, Spencer H Conner3, Gipsy Majumdar3, Solomon S Solomon4. 1. Departments of Medicine and Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38163, USA; Medicine and Research Services, Veterans Association Medical Center, Memphis, TN 38104, USA; Wellcome Trust Medical Research Council Institute of Metabolic Science, Cambridge CB2 0QQ, UK; National Institute of Diabetes & Digestive & Kidney Disease, National Institutes of Health, Bethesda, MD 20892, USA. 2. Medicine and Research Services, Veterans Association Medical Center, Memphis, TN 38104, USA. 3. Departments of Medicine and Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38163, USA; Medicine and Research Services, Veterans Association Medical Center, Memphis, TN 38104, USA. 4. Departments of Medicine and Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38163, USA; Medicine and Research Services, Veterans Association Medical Center, Memphis, TN 38104, USA. Electronic address: ssolomon@uthsc.edu.
Abstract
AIMS/HYPOTHESIS: PTEN may play a reversible role in TNFα induced insulin resistance, which has been linked to obesity-associated insulin resistance (IR). METHODS: Western blots for PTEN and p-Akt were performed on H-411E liver cells incubated with insulin, TNFα, and in selected experiments VO-OHpic vanadium complex in the presence and absence of PTEN siRNA. Total PTEN was compared to β-actin loading control and p-Akt was compared to total Akt. RESULTS: Western blot and Real Time RT-PCR experiments showed increased PTEN after TNFα treatment (p = 0.04); slightly decreased PTEN after insulin treatment; and slightly increased PTEN after insulin + TNFα treatment. PTEN siRNA markedly inhibited the TNFα-induced increase in PTEN (p < 0.01) without significantly changing the p-Akt levels. The vanadium complex, exhibiting insulin-like effects, also significantly prevented the TNFα-induced increase in PTEN. Combining insulin and VO-OHpic was additive, providing both proof of concept and insight into mechanism. DISCUSSION: The PTEN increase due to TNFα treatment was reversible by both PTEN siRNA knockdown and VO-OHpic treatment. Thus, PTEN is identified as a potential new therapeutic target for reducing IR in Type 2 DM. Published by Elsevier Inc.
AIMS/HYPOTHESIS: PTEN may play a reversible role in TNFα induced insulin resistance, which has been linked to obesity-associated insulin resistance (IR). METHODS: Western blots for PTEN and p-Akt were performed on H-411E liver cells incubated with insulin, TNFα, and in selected experiments VO-OHpic vanadium complex in the presence and absence of PTEN siRNA. Total PTEN was compared to β-actin loading control and p-Akt was compared to total Akt. RESULTS: Western blot and Real Time RT-PCR experiments showed increased PTEN after TNFα treatment (p = 0.04); slightly decreased PTEN after insulin treatment; and slightly increased PTEN after insulin + TNFα treatment. PTEN siRNA markedly inhibited the TNFα-induced increase in PTEN (p < 0.01) without significantly changing the p-Akt levels. The vanadium complex, exhibiting insulin-like effects, also significantly prevented the TNFα-induced increase in PTEN. Combining insulin and VO-OHpic was additive, providing both proof of concept and insight into mechanism. DISCUSSION: The PTEN increase due to TNFα treatment was reversible by both PTEN siRNA knockdown and VO-OHpic treatment. Thus, PTEN is identified as a potential new therapeutic target for reducing IR in Type 2 DM. Published by Elsevier Inc.
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