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Mechanisms by Which Liver-Specific PEPCK Knockout Mice Preserve Euglycemia During Starvation

Authors :
Paul J. Flakoll
Craig R. Malloy
Mark A. Magnuson
A. Dean Sherry
Pengxiang She
E. Patrick Donahue
Shawn C. Burgess
Masakazu Shiota
Source :
Diabetes. 52:1649-1654
Publication Year :
2003
Publisher :
American Diabetes Association, 2003.

Abstract

Liver-specific PEPCK knockout mice, which are viable despite markedly abnormal lipid metabolism, exhibit mild hyperglycemia in response to fasting. We used isotopic tracer methods, biochemical measurements, and nuclear magnetic resonance spectroscopy to show that in mice lacking hepatic PEPCK, 1) whole-body glucose turnover is only slightly decreased; 2) whole-body gluconeogenesis from phosphoenolpyruvate, but not from glycerol, is moderately decreased; 3) tricarboxylic acid cycle activity is globally increased, even though pyruvate cycling and anaplerosis are decreased; 4) the liver is unable to synthesize glucose from lactate/pyruvate and produces only a minimal amount of glucose; and 5) glycogen synthesis in both the liver and muscle is impaired. Thus, although mice without hepatic PEPCK have markedly impaired hepatic gluconeogenesis, they are able to maintain a near-normal blood glucose concentration while fasting by increasing extrahepatic gluconeogenesis coupled with diminishing whole-body glucose utilization.

Details

ISSN :
1939327X and 00121797
Volume :
52
Database :
OpenAIRE
Journal :
Diabetes
Accession number :
edsair.doi.dedup.....580d62b75a58a7702ea128b3aa36a45a
Full Text :
https://doi.org/10.2337/diabetes.52.7.1649