Short-term overexpression of a constitutively active form of AMP-activated protein kinase in the liver leads to mild hypoglycemia and fatty liver.

Details

Serval ID
serval:BIB_AD2F12020C42
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Short-term overexpression of a constitutively active form of AMP-activated protein kinase in the liver leads to mild hypoglycemia and fatty liver.
Journal
Diabetes
Author(s)
Foretz M., Ancellin N., Andreelli F., Saintillan Y., Grondin P., Kahn A., Thorens B., Vaulont S., Viollet B.
ISSN
0012-1797
Publication state
Published
Issued date
2005
Peer-reviewed
Oui
Volume
54
Number
5
Pages
1331-1339
Language
english
Abstract
AMP-activated protein kinase (AMPK) is a major therapeutic target for the treatment of diabetes. We investigated the effect of a short-term overexpression of AMPK specifically in the liver by adenovirus-mediated transfer of a gene encoding a constitutively active form of AMPKalpha2 (AMPKalpha2-CA). Hepatic AMPKalpha2-CA expression significantly decreased blood glucose levels and gluconeogenic gene expression. Hepatic expression of AMPKalpha2-CA in streptozotocin-induced and ob/ob diabetic mice abolished hyperglycemia and decreased gluconeogenic gene expression. In normal mouse liver, AMPKalpha2-CA considerably decreased the refeeding-induced transcriptional activation of genes encoding proteins involved in glycolysis and lipogenesis and their upstream regulators, SREBP-1 (sterol regulatory element-binding protein-1) and ChREBP (carbohydrate response element-binding protein). This resulted in decreases in hepatic glycogen synthesis and circulating lipid levels. Surprisingly, despite the inhibition of hepatic lipogenesis, expression of AMPKalpha2-CA led to fatty liver due to the accumulation of lipids released from adipose tissue. The relative scarcity of glucose due to AMPKalpha2-CA expression led to an increase in hepatic fatty acid oxidation and ketone bodies production as an alternative source of energy for peripheral tissues. Thus, short-term AMPK activation in the liver reduces blood glucose levels and results in a switch from glucose to fatty acid utilization to supply energy needs.
Keywords
AMP-Activated Protein Kinases, Animals, Base Sequence, Blood Glucose, Cloning, Molecular, DNA Primers, Enzyme Activation, Fatty Acids, Fatty Liver, Hepatocytes, Hypoglycemia, Kinetics, Liver, Mice, Mice, Inbred C57BL, Mice, Obese, Multienzyme Complexes, Protein-Serine-Threonine Kinases, Recombinant Proteins, Reverse Transcriptase Polymerase Chain Reaction, Transfection
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 13:41
Last modification date
20/08/2019 15:17
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