Development of whole-body and skeletal muscle insulin resistance after one day of hindlimb suspension

• Published in: Metabolism, clinical and experimental Vol. 53; no. 9; pp. 1215 - 1222
• Main Authors: O’Keefe, Matthew P., Perez, Felipe R., Kinnick, Tyson R., Tischler, Marc E., Henriksen, Erik J.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-09-2004; Elsevier
• Subjects: Animals; Biological and medical sciences; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Glucose - metabolism; Glucose Tolerance Test; Glucose Transporter Type 4; Hindlimb Suspension - physiology; Insulin Receptor Substrate Proteins; Insulin Resistance - physiology; Medical sciences; Mitogen-Activated Protein Kinases - metabolism; Monosaccharide Transport Proteins - metabolism; Muscle Proteins - biosynthesis; Muscle Proteins - metabolism; Muscle, Skeletal - physiology; Oncogene Protein v-akt; Organ Size - physiology; p38 Mitogen-Activated Protein Kinases; Phosphatidylinositol 3-Kinases - metabolism; Phosphoproteins - metabolism; Rats; Rats, Sprague-Dawley; Receptor, Insulin - metabolism; Retroviridae Proteins, Oncogenic - metabolism; Signal Transduction; Space life sciences; Triglycerides - metabolism; Pancreatic hormone; Hindlimb; Rat; Activity; Glucose; Soleus muscle; Female; Whole body; Child; Human; Acute; Rodentia; Tolerance; Suspension; Striated muscle; Insulin; Target tissue resistance; Vertebrata; Sensitivity; Weight control; Mammalia; Aminoacid; Animal; Nitric oxide; Transport; Comparative study; NASA Discipline Musculoskeletal; Non-NASA Center
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2004.02.025

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 β-subunit (IR-β), 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-β 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.