Insulin resistance and neurodegeneration: Roles of obesity, type 2 diabetes mellitus and non-alcoholic steatohepatitis

被引：0

作者：

de la Monte, Suzanne M. ^{[1
,2
,3
]}

Longato, Lisa ^{[1
]}

Tong, Ming ^{[1
,4
,5
]}

Wands, Jack R. ^{[1
,4
,5
]}

机构：

[1] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA

[2] Rhode Isl Hosp, Div Neuropathol, Dept Pathol, Providence, RI 02903 USA

[3] Rhode Isl Hosp, Dept Neurol, Providence, RI 02903 USA

[4] Rhode Isl Hosp, Dept Med, Div Gastroenterol, Providence, RI 02903 USA

[5] Rhode Isl Hosp, Liver Res Ctr, Providence, RI 02903 USA

来源：

CURRENT OPINION IN INVESTIGATIONAL DRUGS | 2009年 / 10卷 / 10期

关键词：

BBB; blood-brain barrier; ceramide; dementia; insulin resistance; liver-brain axis; obesity; type 2 diabetes mellitus; FATTY LIVER-DISEASE; GROWTH-FACTOR-I; CENTRAL-NERVOUS-SYSTEM; NECROSIS-FACTOR-ALPHA; CHRONIC HEPATITIS-C; ALZHEIMERS-DISEASE; INTRANASAL INSULIN; MOLECULAR-MECHANISMS; SKELETAL-MUSCLE; FACTOR EXPRESSION;

D O I：

暂无

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Recent studies have linked obesity, type 2 diabetes mellitus (T2DM) or non-alcoholic steatohepatitis (NASH) to insulin resistance in the brain, cognitive impairment and neurodegeneration. Insulin resistance compromises cell survival, metabolism and neuronal plasticity, and increases oxidative stress, cytokine activation and apoptosis. T2DM/NASH has been demonstrated to be associated with increased ceramide generation, suggesting a mechanistic link between peripheral insulin resistance and neurodegeneration because ceramides mediate insulin resistance and can cross the blood-brain barrier (BBB). Peripheral insulin resistance diseases may potentially cause brain insulin resistance via a liver-brain axis of neurodegeneration as a result of the trafficking of ceramides across the BBB. Therapy that includes insulin-sensitizing agents may help prevent brain insulin resistance-mediated cognitive impairment.

引用

页码：1049 / 1060

页数：12

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