An “up, no change, or down” system: Time-dependent expression of mRNAs in contused skeletal muscle of rats used for wound age estimation

Although blood flow in the microcirculation of the rat skeletal muscle has negligible inertia forces with very low Reynolds number and Womersley parameter, time-dependent pressure and flow variations can be observed. Such phenomena include, for example, arterial flow overshoot following a step arterial pressure, a gradual arterial pressure reduction for a step flow, or hysteresis between pressure and flow when a pulsatile pressure is applied. Arterial and venous flows do not follow the same time course during such transients. A theoretical analysis is presented for these phenomena using a microvessel with distensible viscoelastic walls and purely viscous flow subject to time variant arterial pressures. The results indicate that the vessel distensibility plays an important role in such time-dependent microvascular flow and the effects are of central physiological importance during normal muscle perfusion. In-vivo whole organ pressure-flow data in the dilated rat gracilis muscle agree in the time course with the theoretical predictions. Hemodynamic impedances of the skeletal muscle microcirculation are investigated for small arterial and venous pressure amplitudes superimposed on an initial steady flow and pressure drop along the vessel.

Download Full-text

14-Deoxy-11,12-Didehydroandrographolide Ameliorates Glucose Intolerance Enhancing the LKB1/AMPKα/TBC1D1/GLUT4 Signaling Pathway and Inducing GLUT4 Expression in Myotubes and Skeletal Muscle of Obese Mice

The American Journal of Chinese Medicine ◽

10.1142/s0192415x21500695 ◽

2021 ◽

pp. 1-19

Author(s):

Chih-Chieh Chen ◽

Chong-Kuei Lii ◽

Chia-Wen Lo ◽

Yi-Hsueh Lin ◽

Ya-Chen Yang ◽

...

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Glucose Uptake ◽

Signaling Pathway ◽

Nuclear Translocation ◽

Time Dependent ◽

Antidiabetic Activity ◽

C2c12 Myotubes ◽

Dependent Manner ◽

Compound C

14-Deoxy-11,12-didehydroandrographolide (deAND), a bioactive component of Andrographis paniculata, has antidiabetic activity. AMP-activated protein kinase (AMPK) regulates glucose transport and ameliorates insulin resistance. The aim of the present study was to investigate whether activation of AMPK is involved in the mechanism by which deAND ameliorates insulin resistance in muscles. deAND amounts up to 40 [Formula: see text]M dose-dependently activated phosphorylation of AMPK[Formula: see text] and TBC1D1 in C2C12 myotubes. In addition, deAND significantly activated phosphorylation of LKB1 at 6 h after treatment, and this activation was maintained up to 48 h. deAND increased glucose uptake at 18 h after treatment, and this increase was time dependent up to 72 h. Compound C, an inhibitor of AMPK, suppressed deAND-induced phosphorylation of AMPK[Formula: see text] and TBC1D1 and reversed the effect on glucose uptake. In addition, the expression of GLUT4 mRNA and protein in C2C12 myotubes was up-regulated by deAND in a time-dependent manner. Promotion of GLUT4 gene transcription was verified by a pGL3-GLUT4 (837 bp) reporter assay. deAND also increased the nuclear translocation of MEF-2A and PPAR[Formula: see text]. After 16 weeks of feeding, the high-fat diet (HFD) inhibited phosphorylation of AMPK[Formula: see text] and TBC1D1 in skeletal muscle of obese C57BL/6JNarl mice, and deactivation of AMPK[Formula: see text] and TBC1D1 by the HFD was abolished by deAND supplementation. Supplementation with deAND significantly promoted membrane translocation of GLUT4 compared with the HFD group. Supplementation also significantly increased GLUT4 mRNA and protein expression in skeletal muscle compared with the HFD group. The hypoglycemic effects of deAND are likely associated with activation of the LKB1/AMPK[Formula: see text]/TBC1D1/GLUT4 signaling pathway and stimulation of MEF-2A- and PPAR[Formula: see text]-dependent GLUT4 gene expression, which account for the glucose uptake into skeletal muscle and lower blood glucose levels.

Download Full-text

Evidence for a Specific Uptake and Retention Mechanism for 25-Hydroxyvitamin D (25OHD) in Skeletal Muscle Cells

Endocrinology ◽

10.1210/en.2012-2245 ◽

2013 ◽

Vol 154 (9) ◽

pp. 3022-3030 ◽

Cited By ~ 64

Author(s):

M. Abboud ◽

D. A. Puglisi ◽

B. N. Davies ◽

M. Rybchyn ◽

N. P. Whitehead ◽

...

Keyword(s):

Skeletal Muscle ◽

Protein A ◽

In Vitro Release ◽

Muscle Cells ◽

Retention Mechanism ◽

Time Dependent ◽

Hydroxyvitamin D ◽

Mg63 Cells ◽

25 Hydroxyvitamin D

Little is known about the mechanism for the prolonged residence time of 25-hydroxyvitamin D (25OHD) in blood. Several lines of evidence led us to propose that skeletal muscle could function as the site of an extravascular pool of 25OHD. In vitro studies investigated the capacity of differentiated C2 murine muscle cells to take up and release 25OHD, in comparison with other cell types and the involvement of the membrane protein megalin in these mechanisms. When C2 cells are differentiated into myotubes, the time-dependent uptake of labeled 25OHD is 2–3 times higher than in undifferentiated myoblasts or nonmuscle osteoblastic MG63 cells (P < .001). During in vitro release experiments (after 25OHD uptake), myotubes released only 32% ± 6% stored 25OHD after 4 hours, whereas this figure was 60% ± 2% for osteoblasts (P < .01). Using immunofluorescence, C2 myotubes and primary rat muscle fibers were, for the first time, shown to express megalin and cubilin, endocytotic receptors for the vitamin D binding protein (DBP), which binds nearly all 25OHD in the blood. DBP has a high affinity for actin in skeletal muscle. A time-dependent uptake of Alexafluor-488-labeled DBP into mature muscle cells was observed by confocal microscopy. Incubation of C2 myotubes (for 24 hours) with receptor-associated protein, a megalin inhibitor, led to a 40% decrease in 25OHD uptake (P < .01). These data support the proposal that 25OHD, after uptake into mature muscle cells, is held there by DBP, which has been internalized via membrane megalin and is retained by binding to actin.

Download Full-text