Insulin-dependent Diabetes Mellitus Enhances Microvascular Permeability and Induces Atrophy of Rat Skeletal Muscle

̶ In vivo Imaging using Two-photon Laser Scanning Microscopy ̶

抄録

[Background/Purpose]

Patients with diabetes mellitus (DM) have reduced skeletal muscle mass, resulting in functional incapacity. Hyperglycemia impairs vascular endothelial function of skeletal muscle. Although endothelium has a crucial role as muscle-blood barrier (MBB) through modulating microvascular permeability, there is no direct evidence showing relationship between MBB impairment and skeletal muscle atrophy. The purpose of this study is to assess microvascular permeability of diabetic skeletal muscle by a novel in vivo imaging using two-photon laser scanning microscopy (TPLSM).

[Methods]

Wistar male rats (10 wks old, n=10) were divided into streptozocin-induced insulin-dependent DM (n=5) and control groups (n=5). Fluorescent dye (rhodamine b dextran, 70 kDa) was intravenously infused and then 3D images of extravasation in exposed tibialis anterior (TA) muscle were obtained by TPLSM. Interstitial leakage volume of fluorescent dye was calculated by image analysis, and was compared between DM and control rats.

[Results]

The leakage volume was significantly higher in DM compared to control rats (11.97 ± 5.71 vs. 44.09 ± 12.19 μ m3 x min x 106, control vs. DM, P=0.04). TA weight divided by body weight (TA/BW) was significantly lower in DM compared to control rats (1.77 ± 0.06 vs. 1.57 ± 0.04 mg/g, control vs. DM, P=0.04). The TA/BW was significantly and negatively correlated with interstitial leakage volume in both groups (R2=0.44, P=0.04).

[Discussion/Conclusion]

These results indicate that insulin-dependent DM impairs MBB, likely resulting in rat skeletal muscle atrophy.

 

[Ethical consideration]

All experiments were conducted under the guidelines estab-lished by the Physiological Society of Japan and were approved by the University of Electro-Communications Institutional Animal Care and Use Committee.