AJP - Endo Journal of Applied Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Endocrinol Metab 282: E38-E45, 2002;
0193-1849/02 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (18)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wu, C.
Right arrow Articles by Lange, A. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wu, C.
Right arrow Articles by Lange, A. J.
Vol. 282, Issue 1, E38-E45, January 2002

Increasing fructose 2,6-bisphosphate overcomes hepatic insulin resistance of type 2 diabetes

Chaodong Wu1, David A. Okar1, Christopher B. Newgard2, and Alex J. Lange1

1 Department of Biochemistry, Molecular Biology and Biophysics, Medical School, University of Minnesota, Minneapolis, Minnesota 55455; and 2 Departments of Biochemistry and Internal Medicine, Touchstone Center for Diabetes Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390

Hepatic glucose production is increased as a metabolic consequence of insulin resistance in type 2 diabetes. Because fructose 2,6-bisphosphate is an important regulator of hepatic glucose production, we used adenovirus-mediated enzyme overexpression to increase hepatic fructose 2,6-bisphosphate to determine if the hyperglycemia in KK mice, polygenic models of type 2 diabetes, could be ameliorated by reduction of hepatic glucose production. Seven days after treatment with virus encoding a mutant 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase designed to increase fructose 2,6-bisphosphate levels, plasma glucose, lipids, and insulin were significantly reduced in KK/H1J and KK.Cg-Ay/J mice. Moreover, high fructose 2,6-bisphosphate levels downregulated glucose-6-phosphatase and upregulated glucokinase gene expression, thereby reversing the insulin-resistant pattern of hepatic gene expression of these two key glucose-metabolic enzymes. The increased hepatic fructose 2,6-bisphosphate also reduced adiposity in both KK mice. These results clearly indicate that increasing hepatic fructose 2,6-bisphosphate overcomes the impairment of insulin in suppressing hepatic glucose production, and it provides a potential therapy for type 2 diabetes.

hepatic glucose production; glucose-6-phosphatase; glucokinase; adenovirus


This article has been cited by other articles:


Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
C. Wu, S. A. Khan, L.-J. Peng, H. Li, S. G. Carmella, and A. J. Lange
Perturbation of glucose flux in the liver by decreasing F26P2 levels causes hepatic insulin resistance and hyperglycemia
Am J Physiol Endocrinol Metab, September 1, 2006; 291(3): E536 - E543.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
L. Massa, S. Baltrusch, D. A. Okar, A. J. Lange, S. Lenzen, and M. Tiedge
Interaction of 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase (PFK-2/FBPase-2) With Glucokinase Activates Glucose Phosphorylation and Glucose Metabolism in Insulin-Producing Cells
Diabetes, April 1, 2004; 53(4): 1020 - 1029.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online