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Elevated extracellular glucose and uncontrolled type 1 diabetes enhance NFAT5 signaling and disrupt the transverse tubular network in mouse skeletal muscle.
- Source :
-
Experimental biology and medicine (Maywood, N.J.) [Exp Biol Med (Maywood)] 2012 Sep; Vol. 237 (9), pp. 1068-83. Date of Electronic Publication: 2012 Sep 10. - Publication Year :
- 2012
-
Abstract
- The transcription factor nuclear factor of activated T-cells 5 (NFAT5) is a key protector from hypertonic stress in the kidney, but its role in skeletal muscle is unexamined. Here, we evaluate the effects of glucose hypertonicity and hyperglycemia on endogenous NFAT5 activity, transverse tubular system morphology and Ca(2+) signaling in adult murine skeletal muscle fibers. We found that exposure to elevated glucose (25-50 mmol/L) increased NFAT5 expression and nuclear translocation, and NFAT-driven transcriptional activity. These effects were insensitive to the inhibition of calcineurin A, but sensitive to both p38α mitogen-activated protein kinases and phosphoinositide 3-kinase-related kinase inhibition. Fibers exposed to elevated glucose exhibited disrupted transverse tubular morphology, characterized by swollen transverse tubules and an increase in longitudinal connections between adjacent transverse tubules. Ca(2+) transients elicited by a single, brief electric field stimuli were increased in amplitude in fibers challenged by elevated glucose. Muscle fibers from type 1 diabetic mice exhibited increased NFAT5 expression and transverse tubule disruptions, but no differences in electrically evoked Ca(2+) transients. Our results suggest the hypothesis that these changes in skeletal muscle could play a role in the pathophysiology of acute and severe hyperglycemic episodes commonly observed in uncontrolled diabetes.
- Subjects :
- Animals
Calcineurin Inhibitors
Calcium Signaling
Mice
Phosphoinositide-3 Kinase Inhibitors
p38 Mitogen-Activated Protein Kinases antagonists & inhibitors
Diabetes Mellitus, Type 1 metabolism
Glucose metabolism
Hyperglycemia metabolism
Muscle Fibers, Skeletal metabolism
Muscle, Skeletal metabolism
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1535-3699
- Volume :
- 237
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Experimental biology and medicine (Maywood, N.J.)
- Publication Type :
- Academic Journal
- Accession number :
- 22966145
- Full Text :
- https://doi.org/10.1258/ebm.2012.012052