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Development of whole-body and skeletal muscle insulin resistance after one day of hindlimb suspension.
- Source :
-
Metabolism: clinical and experimental [Metabolism] 2004 Sep; Vol. 53 (9), pp. 1215-22. - Publication Year :
- 2004
-
Abstract
- Hindlimb suspension (HS) of rats is a model of simulated weightlessness and induces dynamic alterations in insulin action. In the present study, the effect of acute (1-day) HS on whole-body glucose tolerance and insulin action on skeletal muscle glucose transport was assessed in juvenile, female Sprague-Dawley rats. Compared to weight-bearing control rats, 1-day HS animals displayed significantly decreased glucose tolerance and diminished whole-body insulin sensitivity. Glucose transport activity in the 1-day unweighted soleus muscle was significantly decreased (P <.05) compared to weight-bearing control muscles both in the absence and presence of insulin (2 mU/mL). Insulin-mediated glucose transport activity in the extensor digitorum longus (EDL) muscles also tended (P =.09) to be lower. There was no change in the protein expression of insulin receptor beta-subunit (IR-beta), insulin receptor substrate-1 (IRS-1), IRS-2, the p85 subunit of phosphatidylinositol-3 kinase (PI3-kinase), Akt, and glucose transporter protein 4 (GLUT-4). The activities of these proteins were also unchanged, as insulin-stimulated IR-beta tyrosine phosphorylation, IRS-1 tyrosine phosphorylation, IRS-1-associated p85, and Akt serine phosphorylation were similar to controls. However, basal Akt phosphorylation was significantly depressed (P <.05) in the 1-day HS soleus. In addition, the protein expression and basal phosphorylation of the stress-activated p38 mitogen-activated protein kinase (p38 MAPK) were significantly elevated (P <.05) in the 1-day unweighted soleus. These results indicate that the development of insulin resistance in the 1-day unweighted soleus is not due to impaired functionality of elements involved in the IR/IRS-1/PI3-kinase/Akt signaling pathway. However, activation of p38 MAPK may play a role in this response.
- Subjects :
- Animals
Female
Glucose metabolism
Glucose Tolerance Test
Glucose Transporter Type 4
Insulin Receptor Substrate Proteins
Mitogen-Activated Protein Kinases metabolism
Monosaccharide Transport Proteins metabolism
Muscle Proteins biosynthesis
Muscle Proteins metabolism
Oncogene Protein v-akt
Organ Size physiology
Phosphatidylinositol 3-Kinases metabolism
Phosphoproteins metabolism
Rats
Rats, Sprague-Dawley
Receptor, Insulin metabolism
Retroviridae Proteins, Oncogenic metabolism
Signal Transduction
Triglycerides metabolism
p38 Mitogen-Activated Protein Kinases
Hindlimb Suspension physiology
Insulin Resistance physiology
Muscle, Skeletal physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0026-0495
- Volume :
- 53
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Metabolism: clinical and experimental
- Publication Type :
- Academic Journal
- Accession number :
- 15334387
- Full Text :
- https://doi.org/10.1016/j.metabol.2004.02.025