The long-chain fatty acid receptor, GPR40, and glucolipotoxicity: investigations using GPR40-knockout mice

被引：39

作者：

Brownlie, Ruth ^{[1
]}

Mayers, Rachel M. ^{[1
]}

Pierce, Jackie A. ^{[1
]}

Marley, Anna E. ^{[1
]}

Smith, David M. ^{[1
]}

机构：

[1] AstraZeneca Diabet & Obes Drug Discovery, Macclesfield SK10 4TG, Cheshire, England

来源：

BIOCHEMICAL SOCIETY TRANSACTIONS | 2008年 / 36卷

关键词：

beta-cell; fatty acid; glucolipotoxicity; G-protein-coupled receptor 40 (GPR40); islet of Langerhans;

D O I：

10.1042/BST0360950

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：

GPR40 (G-protein-coupled receptor 40) has been shown to be a physiologically relevant receptor for long-chain fatty acids. it is a family A G-protein-coupled receptor highly expressed in the beta-cell where it increases insulin secretion by signalling via G(q) and phospholipase C. Fatty acids are well known to mediate both acute stimulatory effects and chronic detrimental effects on the beta-cell. GPR40-transgenic and GPR40(-/-) animals have been important tools in studies of the metabolic effects of GPR40. In the present article, we review the literature on transgenic GPR40 models and present some of our own studies on the effects of a high-fat diet on the metabolic phenotype of GPR(-/-) mice. GPR40 ligands represent interesting novel therapies for Type 2 diabetes but it is presently unclear whether agonists or antagonists represent the best therapeutic approach.

引用

页码：950 / 954

页数：5

共 26 条

[1] Too much of a good thing: why it is bad to stimulate the beta cell to secrete insulin [J].

Aston-Mourney, K. ;

Proietto, J. ;

Morahan, G. ;

Andrikopoulos, S. .

DIABETOLOGIA, 2008, 51 (04) :540-545

[2] Pharmacological regulation of insulin secretion in MIN6 cells through the fatty acid receptor GPR40: identification of agonist and antagonist small molecules [J].

Briscoe, Celia P. ;

Peat, Andrew J. ;

McKeown, Stephen C. ;

Corbett, David F. ;

Goetz, Aaron S. ;

Littleton, Thomas R. ;

McCoy, David C. ;

Kenakin, Terry P. ;

Andrews, John L. ;

Ammala, Carina ;

Fornwald, James A. ;

Ignar, Diane M. ;

Jenkinson, Stephen .

BRITISH JOURNAL OF PHARMACOLOGY, 2006, 148 (05) :619-628

[3] The orphan G protein-coupled receptor GPR40 is activated by medium and long chain fatty acids [J].

Briscoe, CP ;

Tadayyon, M ;

Andrews, JL ;

Benson, WG ;

Chambers, JK ;

Eilert, MM ;

Ellis, C ;

Elshourbagy, NA ;

Goetz, AS ;

Minnick, DT ;

Murdock, PR ;

Sauls, HR ;

Shabon, U ;

Spinage, LD ;

Strum, JC ;

Szekeres, PG ;

Tan, KB ;

Way, JM ;

Ignar, DM ;

Wilson, S ;

Muir, AI .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (13) :11303-11311

[4]

DUTTAROY A, 2008, AM DIAB ASS 68 SCI S

[5]

FODGREN E, 2007, BIOCHEM BIOPH RES CO, V354, P240

[6] Oleic acid interacts with GPR40 to induce Ca2+ signaling in rat islet β-cells:: mediation by PLC and L-type Ca2+ channel and link to insulin release [J].

Fujiwara, K ;

Maekawa, F ;

Yada, T .

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2005, 289 (04) :E670-E677

[7] Effect of high-fat diet on glucose homeostasis and gene expression in glucokinase knockout mice [J].

Gorman, T. ;

Hope, D. C. D. ;

Brownlie, R. ;

Yu, A. ;

Gill, D. ;

Lofvenmark, J. ;

Wedin, M. ;

Mayers, R. M. ;

Snaith, M. R. ;

Smith, D. M. .

DIABETES OBESITY & METABOLISM, 2008, 10 (10) :885-897

[8] Free fatty acids regulate insulin secretion from pancreatic β cells through GPR40 [J].

Itoh, Y ;

Kawamata, Y ;

Harada, M ;

Kobayashi, M ;

Fujii, R ;

Fukusumi, S ;

Ogi, K ;

Hosoya, M ;

Tanaka, Y ;

Uejima, H ;

Tanaka, H ;

Maruyama, M ;

Satoh, R ;

Okubo, S ;

Kizawa, H ;

Komatsu, H ;

Matsumura, F ;

Noguchi, Y ;

Shinobara, T ;

Hinuma, S ;

Fujisawa, Y ;

Fujino, M .

NATURE, 2003, 422 (6928) :173-176

[9] Glucose-dependent modulation of insulin secretion and intracellular calcium ions by GKA50, a glucokinase activator [J].

Johnson, Daniel ;

Shepherd, Ruth M. ;

Gill, Debra ;

Gorman, Tracy ;

Smith, David M. ;

Dunne, Mark J. .

DIABETES, 2007, 56 (06) :1694-1702

[10] The fatty acid receptor GPR40 plays a role in insulin secretion in vivo after high-fat feeding [J].

Kebede, Melkam ;

Alquier, Thierry ;

Latour, Martin G. ;

Semache, Meriem ;

Tremblay, Caroline ;

Poitout, Vincent .

DIABETES, 2008, 57 (09) :2432-2437

← 1 2 3 →