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Fructose‐induced neurogenic hypertension is mediated by superoxide overexpression and stimulates p38 MAPK‐induced central insulin resistance in the central nervous system
Author(s) -
Chen HsinHung,
Cheng PeiWen,
Tseng ChingJiunn
Publication year - 2017
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.31.1_supplement.883.3
Subject(s) - insulin resistance , medicine , fructose , endocrinology , insulin , insulin receptor , nitric oxide , superoxide , chemistry , biochemistry , enzyme
Type 2 diabetes are at a high risk of complications related to hypertension, and reports have indicated that insulin levels may be associated with blood pressure (BP). Fructose intake has recently been reported to promote insulin resistance and superoxide formation. The aim of this study is to investigate whether fructose intake can enhance superoxide generation and impair insulin signaling in the nucleus tractus solitarii (NTS) and subsequently elevate BP in rats with fructose‐induced hypertension. Treatment with fructose for 4 weeks increased the BP, serum fasting insulin, glucose, homeostatic model assessment‐insulin resistance, and triglyceride levels and reduced the serum direct high‐density lipoprotein level in the fructose group. Treatment with tempol recovered the fructose‐induced decrease in nitric oxide production in the NTS. Immunoblotting and immunofluorescence analyses further showed that fructose increased the p38‐ and fructose‐induced phosphorylation of insulin receptor substrate 1 (IRS1S307) and suppressed AktS473 and neuronal nitric oxide synthase phosphorylation. Similarly, fructose was able to impair insulin sensitivity and increase insulin levels in the NTS. Fructose intake also increased the production of superoxide in the NTS. The results of this study suggest that fructose might induce central insulin resistance and elevate BP by enhancing superoxide production and activating p38 phosphorylation in the NTS. Support or Funding Information MOST104‐2320‐B‐075B‐003‐MY3 1 General Characteristics of the 3 Groups of RatsControl Fructose Fructose + PioglitazoneBody weight (gm) 233 ± 6.6 227.5 ± 10.3 225 ± 6.7 Systolic blood pressure (mmHg) 128.4 ± 2.6 151.9 ± 2.3 * 135.9 ± 5.3 †Mean blood pressure (mmHg) 113.7 ± 0.94 135.8 ± 1.7 * 117.2 ± 3.2 †Fasting serum glucose (mg/dL) 110 ± 2.35 240.3 ± 12.7 * 134.7 ± 18.2 †Fasting serum insulin (pmol/L) 9.38 ± 0.36 175.7 ± 24.5 * 26.69 ± 1.9 †HOMA‐IR Index 0.38 ± 0.02 13.1 ± 2.9 * 1.64 ± 0.23 †dHDL (mg/dL) 68.8 ± 0.67 55.0 ± 1.00 * 69.7 ± 0.88 †Triglyceride (mg/dL) 56.4 ± 3.0 111.5 ± 8.96 * 47.6 ± 9.2 †Cholesterol (mg/dL) 96.6 ± 1.78 100.63 ± 3.97 89.0 ± 1.2 NTS insulin (pmol/L/g protein) 7.97 ± 0.37 18.52 ± 1.73 * 8.08 ± 0.32 †NTS insulin response (mmHg) −24.62 ± 2.4 −8.86 ± 2.17 * −24.3 ± 2.2 †