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  4. Restoration of direct pathway glycogen synthesis flux in the STZ-diabetes rat model by insulin administration
 
research article

Restoration of direct pathway glycogen synthesis flux in the STZ-diabetes rat model by insulin administration

Soares, Ana F.  
•
Carvalho, Rui A.
•
Veiga, Francisco J.
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2012
American journal of physiology. Endocrinology and metabolism

Type 1 diabetes subjects are characterized by impaired direct pathway synthesis of hepatic glycogen that is unresponsive to insulin therapy. Since it is not known whether this is an irreversible defect of insulin-dependent diabetes, direct and indirect pathway glycogen fluxes were quantified in streptozotocin (STZ)-induced diabetic rats and compared with STZ rats that received subcutaneous or intraperitoneal insulin (I-SC or I-IP). Three groups of STZ rats were studied at 18 days post-STZ treatment. One group was administered I-SC and another I-IP as two daily injections of short-acting insulin at the start of each light and dark period for days 9-18. A third group did not receive any insulin, and a fourth group of nondiabetic rats was used as control. Glycogen synthesis via direct and indirect pathways, de novo lipogenesis, and gluconeogenesis were determined over the nocturnal feeding period using deuterated water. Direct pathway was residual in STZ rats, and glucokinase activity was also reduced significantly from control levels. Insulin administration restored both net glycogen synthesis via the direct pathway and glucokinase activity to nondiabetic control levels and improved the lipogenic pathway despite an inefficient normalization of the gluconeogenic pathway. We conclude that the reduced direct pathway flux is not an irreversible defect of insulin-dependent diabetes.

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Type
research article
DOI
10.1152/ajpendo.00161.2012
Author(s)
Soares, Ana F.  
Carvalho, Rui A.
Veiga, Francisco J.
Alves, Marco G.
Martins, Fátima O.
Viegas, Ivan
González, Juan D.
Metón, Isidoro
Baanante, Isabel V.
Jones, John G.
Date Issued

2012

Published in
American journal of physiology. Endocrinology and metabolism
Volume

303

Issue

7

Start page

E875

End page

85

Editorial or Peer reviewed

REVIEWED

Written at

OTHER

EPFL units
LIFMET  
Available on Infoscience
March 25, 2013
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/90537
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