Glucose infusion causes insulin resistance in skeletal muscle of rats without changes in Akt and AS160 phosphorylation

Hoy, Andrew J., Bruce, Clinton R., Cederberg, Anna, Turner, Nigel, James, David E., Cooney, Gregory J. and Kraegen, Edward W. 2007, Glucose infusion causes insulin resistance in skeletal muscle of rats without changes in Akt and AS160 phosphorylation, American journal of physiology : endocrinology and metabolism, vol. 293, no. 5, pp. E1358-E1364, doi: 10.1152/ajpendo.00133.2007.

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Title Glucose infusion causes insulin resistance in skeletal muscle of rats without changes in Akt and AS160 phosphorylation
Author(s) Hoy, Andrew J.
Bruce, Clinton R.ORCID iD for Bruce, Clinton R. orcid.org/0000-0002-0515-3343
Cederberg, Anna
Turner, Nigel
James, David E.
Cooney, Gregory J.
Kraegen, Edward W.
Journal name American journal of physiology : endocrinology and metabolism
Volume number 293
Issue number 5
Start page E1358
End page E1364
Total pages 7
Publisher American Physiological Society
Place of publication Bethesada, Md.
Publication date 2007
ISSN 0193-1849
1522-1555
Keyword(s) Glucotoxicity
Glycogen
Hyperglycemia
in vivo metabolism
Soleus muscle
Summary Hyperglycemia is a defining feature of Type 1 and 2 diabetes. Hyperglycemia also causes insulin resistance, and our group (Kraegen EW, Saha AK, Preston E, Wilks D, Hoy AJ, Cooney GJ, Ruderman NB. Am J Physiol Endocrinol Metab Endocrinol Metab 290: E471–E479, 2006) has recently demonstrated that hyperglycemia generated by glucose infusion results in insulin resistance after 5 h but not after 3 h. The aim of this study was to investigate possible mechanism(s) by which glucose infusion causes insulin resistance in skeletal muscle and in particular to examine whether this was associated with changes in insulin signaling. Hyperglycemia (∼10 mM) was produced in cannulated male Wistar rats for up to 5 h. The glucose infusion rate required to maintain this hyperglycemia progressively lessened over 5 h (by 25%, P < 0.0001 at 5 h) without any alteration in plasma insulin levels consistent with the development of insulin resistance. Muscle glucose uptake in vivo (44%; P < 0.05) and glycogen synthesis rate (52%; P < 0.001) were reduced after 5 h compared with after 3 h of infusion. Despite these changes, there was no decrease in the phosphorylation state of multiple insulin signaling intermediates [insulin receptor, Akt, AS160 (Akt substrate of 160 kDa), glycogen synthase kinase-3β] over the same time course. In isolated soleus strips taken from control or 1- or 5-h glucose-infused animals, insulin-stimulated 2-deoxyglucose transport was similar, but glycogen synthesis was significantly reduced in the 5-h muscle sample (68% vs. 1-h sample; P < 0.001). These results suggest that the reduced muscle glucose uptake in rats after 5 h of acute hyperglycemia is due more to the metabolic effects of excess glycogen storage than to a defect in insulin signaling or glucose transport.
Language eng
DOI 10.1152/ajpendo.00133.2007
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Persistent URL http://hdl.handle.net/10536/DRO/DU:30067046

Document type: Journal Article
Collections: Faculty of Health
School of Exercise and Nutrition Sciences
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