Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 101, Issue 9, Pages 3112-3117Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0308450100
Keywords
glucose; body weight; obesity; diabetes
Categories
Funding
- NIDDK NIH HHS [DK48105B, R01 DK048105, K08 DK002917, R21DK064317, R21 DK064317, K08DK02917] Funding Source: Medline
Ask authors/readers for more resources
Kv1.3 is a voltage-gated potassium (K) channel expressed in a number of tissues, including fat and skeletal muscle. Channel inhibition improves experimental autoimmune encephalitis, in part by reducing IL-2 and tumor necrosis factor production by peripheral T lymphocytes. Gene inactivation causes mice (Kv1.3-/-) exposed to a high-fat diet to gain less weight and be less obese than littermate control. Interestingly, although Kv1.3-/- mice on the high-calorie diet gain weight, they remain euglycemic, with low blood insulin levels. This observation prompted us to examine the effect of Kv1.3 gene inactivation and inhibition on peripheral glucose homeostasis and insulin sensitivity. Here we show that Kv1.3 gene deletion and channel inhibition increase peripheral insulin sensitivity in vivo. Baseline and insulin-stimulated glucose uptake are increased in adipose tissue and skeletal muscle of Kv1.3-/- mice. Inhibition of Kv1.3 activity facilitates the translocation of the glucose transporter, GLUT4, to the plasma membrane. It also suppresses c-JUN terminal kinase activity in fat and skeletal muscle and decreases IL-6 and tumor necrosis factor secretion by adipose tissue. We conclude that Kv1.3 inhibition improves insulin sensitivity by increasing the amount of GLUT4 at the plasma membrane. These results pinpoint a pathway through which K channels regulate peripheral glucose homeostasis, and identify Kv1.3 as a pharmacologic target for the treatment of diabetes.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available