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The Role of Insulin in the Regulation of PEPCK and Gluconeogenesis In Vivo
models of diabetes, elevated HGP (associated with increased lipolysis and possibly F2,6P
2
, and redirecting gluconeogenically derived
gluconeogenesis) was observed without elevation in PEPCK or G6Pase carbon to glycogen. The rate of GNG flux to G6P does not appear
mRNA expression.
73
Furthermore, analysis of liver biopsies from human sensitive to a physiological hyperinsulinemia. n
patients with type 2 diabetes had the same level of gluconeogenic
mRNA expression as non-diabetic controls.
73
This counters the notion
Christopher J Ramnanan, PhD, is a Post-doctoral Fellow in
that gluconeogenic enzyme mRNA levels are appropriate markers for
the Department of Molecular Physiology and Biophysics
the gluconeogenic pathway, even in a chronic disease state. at Vanderbilt University. His research focuses on the
molecular aspects of insulin-mediated regulation of hepatic
Conclusions
glucose production. Dr Ramnanan has a PhD in biology
from Carleton University.
The regulation of gluconeogenesis by insulin in whole animals is
complex, so it is no surprise that there has been controversy regarding
the sensitivity and mechanism of insulin’s effects on the gluconeogenic
Dale S Edgerton, PhD, is a Research Assistant Professor in
pathway in vivo. Recent evidence in rodents suggesting that the
the Department of Molecular Physiology and Biophysics at
insulin–brain–liver axis can modify GNG flux to G6P (via transcriptional Vanderbilt University. His research focuses on insulin action
regulation of supposed rate-limiting enzymes) can be questioned based
in vivo, especially the ability of hormones to regulate
hepatic glucose production through action in the brain and
on the experimental design used. In any case, insulin action in the brain
mechanisms by which inhaled insulin augments muscle
is likely to be of limited importance to the physiological regulation of glucose uptake. He has a PhD in molecular physiology and
HGP, given that the direct effect of insulin is clearly dominant and occurs
biophysics from Vanderbilt University Medical School,
where he also carried out post-doctoral work.
within a few minutes.
14
Alan D Cherrington, PhD, is a Professor in the Departments
Even though intricate insulin-mediated mechanisms are involved in the
of Molecular Physiology and Biophysics and Medicine,
suppression of PEPCK mRNA expression, eventual decreases in PEPCK
Associate Director of the Diabetes Research and Training
Center, and Jacquelyn A Turner and Dr Dorothy J Turner
protein do not modify GNG flux to G6P in response to acute physiological
Chair in Diabetes Research at Vanderbilt University. His
hyperinsulinemia. This indicates that this enzyme has poor control
work focuses on the role of various hormonal and
strength over the pathway
neuronal factors in regulating liver glucose metabolism. He
in vivo. Physiological increases in insulin
received his PhD in physiology from the University of
modify HGP in vivo by inhibiting glycogenolysis and promoting glycogen
Toronto and carried out post-graduate work at Vanderbilt.
deposition, transiently increasing glycolysis by mediating changes in
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US ENDOCRINOLOGY 39
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