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Title: Role of PTEN in TNFα induced insulin resistance

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. - Highlights: • TNFα treatment induced a significant increase in PTEN in H-411E liver cells. • PTEN siRNA knockdown prevented this effect. • VO-OHpicmore » (vanadium complex) treatment, like insulin, decreased PTEN protein levels. • Thus, PTEN is identified as a potential therapeutic target in DM Type 2.« less
Authors:
 [1] ;  [2] ;  [3] ;  [2] ;  [4] ; ;  [1] ;  [2] ;  [1] ;  [2]
  1. Departments of Medicine and Pharmacology, University of Tennessee Health Science Center, Memphis, TN 38163 (United States)
  2. (United States)
  3. (United Kingdom)
  4. Medicine and Research Services, Veterans Association Medical Center, Memphis, TN 38104 (United States)
Publication Date:
OSTI Identifier:
22462071
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 461; Journal Issue: 3; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACTIN; ADDITIVES; BLOOD; CHROMOSOMES; COMPARATIVE EVALUATIONS; CONTROL; FASTING; GLUCOSE; HYPOTHESIS; INSULIN; LIVER CELLS; MEMBRANES; METABOLIC DISEASES; POLYMERASE CHAIN REACTION; POLYVINYLS; RECEPTORS; VANADIUM; VANADIUM COMPLEXES