The PI3K/AKT pathway in obesity and type 2 diabetes

被引：1268

作者：

Huang, Xingjun ^{[1
,2
]}

Liu, Guihua ^{[3
]}

Guo, Jiao ^{[2
]}

Su, Zhengquan ^{[1
,2
]}

机构：

[1] Guangdong Pharmaceut Univ, Guangdong Engn Res Ctr Nat Prod & New Drugs, Guangdong Prov Univ Engn Technol Res Ctr Nat Prod, Guangzhou 510006, Guangdong, Peoples R China

[2] Guangdong Pharmaceut Univ, Guangdong Metab Dis Res Ctr Integrated Chinese &, Guangzhou 510006, Guangdong, Peoples R China

[3] Shenzhen Ctr Dis Control & Prevent, 8 Longyuan Rd, Shenzhen 518055, Peoples R China

来源：

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES | 2018年 / 14卷 / 11期

基金：

美国国家科学基金会;

关键词：

PROTEIN-KINASE-B; HEPATIC GLUCOSE-PRODUCTION; HYPOTHALAMIC INSULIN-RESISTANCE; RECEPTOR SUBSTRATE 2; FATTY LIVER-DISEASE; BETA-CELL MASS; MTOR COMPLEX 1; P70; S6; KINASE; SKELETAL-MUSCLE; AGRP NEURONS;

D O I：

10.7150/ijbs.27173

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Obesity and type 2 diabetes mellitus are complicated metabolic diseases that affect multiple organs and are characterized by hyperglycaemia. Currently, stable and effective treatments for obesity and type 2 diabetes mellitus are not available. Therefore, the mechanisms leading to obesity and diabetes and more effective ways to treat obesity and diabetes should be identified. Based on accumulated evidences, the PI3K/AKT signalling pathway is required for normal metabolism due to its characteristics, and its imbalance leads to the development of obesity and type 2 diabetes mellitus. This review focuses on the role of PI3K/AKT signalling in the skeletal muscle, adipose tissue, liver, brain and pancreas, and discusses how this signalling pathway affects the development of the aforementioned diseases. We also summarize evidences for recently identified therapeutic targets of the PI3K/AKT pathway as treatments for obesity and type 2 diabetes mellitus. PI3K/AKT pathway damaged in various tissues of the body leads to obesity and type 2 diabetes as the result of insulin resistance, and in turn, insulin resistance exacerbates the PI3K/AKT pathway, forming a vicious circle.

引用

页码：1483 / 1496

页数：14

共 171 条

[1] The critical role of Akt in cardiovascular function [J].

Abeyrathna, Prasanna ;

Su, Yunchao .

VASCULAR PHARMACOLOGY, 2015, 74 :38-48

[2] Role of leptin in the neuroendocrine response to fasting [J].

Ahima, RS ;

Prabakaran, D ;

Mantzoros, C ;

Qu, DQ ;

Lowell, B ;

MaratosFlier, E ;

Flier, JS .

NATURE, 1996, 382 (6588) :250-252

[3] Differential regulation of adipocyte PDE3B in distinct membrane compartments by insulin and the β3-adrenergic receptor agonist CL316243: effects of caveolin-1 knockdown on formation/maintenance of macromolecular signalling complexes [J].

Ahmad, Faiyaz ;

Lindh, Rebecka ;

Tang, Yan ;

Ruishalme, Iida ;

Ost, Anita ;

Sahachartsiri, Bobby ;

Stralfors, Peter ;

Degerman, Eva ;

Manganiello, Vincent C. .

BIOCHEMICAL JOURNAL, 2009, 424 :399-410

[4] Dominant Role of the p110β Isoform of PI3K over p110α in Energy Homeostasis Regulation by POMC and AgRP Neurons [J].

Al-Qassab, Hind ;

Smith, Mark A. ;

Irvine, Elaine E. ;

Guillermet-Guibert, Julie ;

Claret, Marc ;

Choudhury, Agharul I. ;

Selman, Colin ;

Piipari, Kaisa ;

Clements, Melanie ;

Lingard, Steven ;

Chandarana, Keval ;

Bell, Jimmy D. ;

Barsh, Gregory S. ;

Smith, Andrew J. H. ;

Batterham, Rachel L. ;

Ashford, Michael L. J. ;

Vanhaesebroeck, Bart ;

Withers, Dominic J. .

CELL METABOLISM, 2009, 10 (05) :343-354

[5] mTORC1 signaling in Agrp neurons mediates circadian expression of Agrp and NPY but is dispensable for regulation of feeding behavior [J].

Albert, Verena ;

Cornu, Marion ;

Hall, Michael N. .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2015, 464 (02) :480-486

[6] Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase B alpha [J].

Alessi, DR ;

James, SR ;

Downes, CP ;

Holmes, AB ;

Gaffney, PRJ ;

Reese, CB ;

Cohen, P .

CURRENT BIOLOGY, 1997, 7 (04) :261-269

[7] Molecular basis for the substrate specificity of protein kinase B; Comparison with MAPKAP kinase-1 and p70 S6 kinase [J].

Alessi, DR ;

Caudwell, FB ;

Andjelkovic, M ;

Hemmings, BA ;

Cohen, P .

FEBS LETTERS, 1996, 399 (03) :333-338

[8] Interleukin-1 effect on glycemia in the non-obese diabetic mouse at the pre-diabetic stage [J].

Amrani, A ;

JafarianTehrani, M ;

Mormede, P ;

Durant, S ;

Pleau, JM ;

Haour, F ;

Dardenne, M ;

HomoDelarche, F .

JOURNAL OF ENDOCRINOLOGY, 1996, 148 (01) :139-148

[9] Activation and phosphorylation of a pleckstrin homology domain containing protein kinase (RAC-PK/PKB) promoted by serum and protein phosphatase inhibitors [J].

Andjelkovic, M ;

Jakubowicz, T ;

Cron, P ;

Ming, XF ;

Han, JW ;

Hemmings, BA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (12) :5699-5704

[10] GDNF rescues hyperglycemia-induced diabetic enteric neuropathy through activation of the PI3K/Akt pathway [J].

Anitha, M ;

Gondha, C ;

Sutliff, R ;

Parsadanian, A ;

Mwangi, S ;

Sitaraman, SV ;

Srinivasan, S .

JOURNAL OF CLINICAL INVESTIGATION, 2006, 116 (02) :344-356

← 1 2 3 4 5 6 7 8 9 10 →