The Role of Adipose Tissue and Lipotoxicity in the Pathogenesis of Type 2 Diabetes

被引：229

作者：

Cusi, Kenneth ^{[1
]}

机构：

[1] Univ Texas Hlth Sci Ctr San Antonio, Diabet Div, San Antonio, TX 78284 USA

来源：

CURRENT DIABETES REPORTS | 2010年 / 10卷 / 04期

关键词：

Adipose tissue; Lipotoxicity; NAFLD; Type 2 diabetes mellitus; Insulin resistance; FREE FATTY-ACIDS; ENCODED MITOCHONDRIAL GENES; IMPAIRS INSULIN-SECRETION; BODY-MASS INDEX; SKELETAL-MUSCLE; FAMILY-HISTORY; HEPATIC STEATOSIS; METABOLIC PROFILE; POTENTIAL ROLE; PLASMA FFA;

D O I：

10.1007/s11892-010-0122-6

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The widespread epidemics of obesity and type 2 diabetes mellitus (T2DM) suggest that both conditions are closely linked. An increasing body of evidence has shifted our view of adipose tissue from a passive energy depot to a dynamic "endocrine organ" that tightly regulates nutritional balance by means of a complex crosstalk of adipocytes with their microenvironment. Dysfunctional adipose tissue, particularly as observed in obesity, is characterized by adipocyte hypertrophy, macrophage infiltration, impaired insulin signaling, and insulin resistance. The result is the release of a host of inflammatory adipokines and excessive amounts of free fatty acids that promote ectopic fat deposition and lipotoxicity in muscle, liver, and pancreatic beta cells. This review focuses on recent work on how glucose homeostasis is profoundly altered by distressed adipose tissue. A better understanding of this relationship offers the best chance for early intervention strategies aimed at preventing the burden of T2DM.

引用

页码：306 / 315

页数：10

共 78 条

[71] Ectopic lipids and organ function [J].

Szendroedi, Julia ;

Roden, Michael .

CURRENT OPINION IN LIPIDOLOGY, 2009, 20 (01) :50-56

[72] Lipotoxicity of β-cells in obesity and in other causes of fatty acid spillover [J].

Unger, RH ;

Zhou, YT .

DIABETES, 2001, 50 :S118-S121

[73] Twins in metabolic and diabetes research: what do they tell us? [J].

Vaag, Allan ;

Poulsen, Pernille .

CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE, 2007, 10 (05) :591-596

[74] Intramyocellular lipid is associated with resistance to in vivo insulin actions on glucose uptake, antilipolysis, and early insulin signaling pathways in human skeletal muscle [J].

Virkamäki, A ;

Korsheninnikova, E ;

Seppälä-Lindroos, A ;

Vehkavaara, S ;

Goto, T ;

Halavaara, J ;

Häkkinen, AM ;

Yki-Järvinen, H .

DIABETES, 2001, 50 (10) :2337-2343

[75] Dietary cholesterol, rather than liver steatosis, leads to hepatic inflammation in hyperlipidemic mouse models of nonalcoholic steatohepatitis [J].

Wouters, Kristiaan ;

van Gorp, Patrick J. ;

Bieghs, Veerle ;

Gijbels, Marion J. ;

Duimel, Hans ;

Luetjohann, Dieter ;

Kerksiek, Anja ;

van Kruchten, Roger ;

Maeda, Nobuyo ;

Staels, Bart ;

van Bilsen, Marc ;

Shiri-Sverdlov, Ronit ;

Hofker, Marten H. .

HEPATOLOGY, 2008, 48 (02) :474-486

[76] Deletion of Fas in adipocytes relieves adipose tissue inflammation and hepatic manifestations of obesity in mice [J].

Wueest, Stephan ;

Rapold, Reto A. ;

Schumann, Desiree M. ;

Rytka, Julia M. ;

Schildknecht, Anita ;

Nov, Ori ;

Chervonsky, Alexander V. ;

Rudich, Assaf ;

Schoenle, Eugen J. ;

Donath, Marc Y. ;

Konrad, Daniel .

JOURNAL OF CLINICAL INVESTIGATION, 2010, 120 (01) :191-202

[77] Evidence of impaired adipogenesis in insulin resistance [J].

Yang, XL ;

Jansson, PA ;

Nagaev, I ;

Jack, MM ;

Carvalho, E ;

Sunnerhagen, KS ;

Cam, MC ;

Cushman, SW ;

Smith, U .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2004, 317 (04) :1045-1051

[78] Emerging role of adipose tissue hypoxia in obesity and insulin resistance [J].

Ye, J. .

INTERNATIONAL JOURNAL OF OBESITY, 2009, 33 (01) :54-66

← 1 2 3 4 5 6 7 8 →