Kv1-3 potassium channel blockade as an approach to insulin resistance

被引:20
作者
Desir, GV [1 ]
机构
[1] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA
关键词
diabetes; obesity; potassium channel;
D O I
10.1517/14728222.9.3.571
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Diabetes mellitus is a devastating metabolic disease caused by either insulin deficiency or resistance and characterised by abnormal glucose, protein and lipid metabolism. It affects > 150 million people worldwide, 14 million in the US alone (90% Type II and 10% Type I) where it accounts for similar to 15% of health-care expenditure. Insulin resistance is a cardinal feature of Type II diabetes. The molecular mechanisms that mediate insulin resistance are under intense scrutiny, and a major goal of this effort is to uncover potential therapeutic targets. Recent data indicate that the voltage-gated potassium channel, Kv1.3, is an important regulator of peripheral insulin sensitivity and glucose metabolism. Indeed, Kv1.3 channel inhibition increases insulin sensitivity by decreasing inflammatory cytokines and by facilitating the translocation of GLUT4 to the plasma membrane. In light of these novel findings, the author believes that Kv1.3 is a promising target for the development of drugs useful in the management of insulin resistance and diabetes.
引用
收藏
页码:571 / 579
页数:9
相关论文
共 68 条
[1]   The c-Jun NH2-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser307 [J].
Aguirre, V ;
Uchida, T ;
Yenush, L ;
Davis, R ;
White, MF .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (12) :9047-9054
[2]  
ARKETT SA, 1994, RECEPTOR CHANNEL, V2, P281
[3]   REGULATION OF A MAJOR CLONED VOLTAGE-GATED K+ CHANNEL FROM HUMAN LYMPHOCYTES-T [J].
ATTALI, B ;
HONORE, E ;
LESAGE, F ;
LAZDUNSKI, M ;
BARHANIN, J .
FEBS LETTERS, 1992, 303 (2-3) :229-232
[4]   Selective blockade of T lymphocyte K+ channels ameliorates experimental autoimmune encephalomyelitis, a model for multiple sclerosis [J].
Beeton, C ;
Wulff, H ;
Barbaria, J ;
Clot-Faybesse, O ;
Pennington, M ;
Bernard, D ;
Cahalan, MD ;
Chandy, KG ;
Béraud, E .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (24) :13942-13947
[5]   Role of fatty acids in the pathogenesis of insulin resistance and NIDDM [J].
Boden, G .
DIABETES, 1997, 46 (01) :3-10
[6]   Modulation of the Kv1.3 potassium channel by receptor tyrosine kinases [J].
Bowlby, MR ;
Fadool, DA ;
Holmes, TC ;
Levitan, IB .
JOURNAL OF GENERAL PHYSIOLOGY, 1997, 110 (05) :601-610
[7]  
Brown H, 1998, GLIA, V22, P94, DOI 10.1002/(SICI)1098-1136(199801)22:1<94::AID-GLIA9>3.0.CO
[8]  
2-8
[9]   Role of brain insulin receptor in control of body weight and reproduction [J].
Brüning, JC ;
Gautam, D ;
Burks, DJ ;
Gillette, J ;
Schubert, M ;
Orban, PC ;
Klein, R ;
Krone, W ;
Müller-Wieland, D ;
Kahn, CR .
SCIENCE, 2000, 289 (5487) :2122-2125
[10]  
CAHALAN MD, 1991, CURR TOP MEMBR, V39, P357