Heat stress, via its effects on muscle intracellular Ca²⁺ concentrations ([Ca²⁺]i), has been invoked as a putative therapeutic countermeasure to Type 1 diabetes-induced muscle atrophy. Using in vivo muscle preparation we tested the hypothesis that impaired muscle Ca²⁺ homeostasis in type I diabetic rats is due to attenuated heat stress tolerance mediated via TRPV1. Male Wistar rats were assigned to 1 of 4 groups: 1.control 30^oC (CONT 30^oC), 2.CONT 40^oC, 3.diabetes 30^oC (DIA 30^oC), 4.DIA 40^oC. 40^oC was selected because it just exceeds the TRPV1 activation threshold. Spinotrapezius muscles were exteriorized in vivo and loaded with the fluorescent Ca²⁺ probe Fura-2AM. [Ca²⁺]i was estimated over 20min using fluorescence microscopy in quiescent muscle held at the required temperature using calibrated heat source applied to the ventral muscle surface. Western blotting was performed to determine the protein expression levels of TRPV1 in spinotrapezius muscle. After 20min of heat stress, the CONT 40^oC condition induced a 12.3% [Ca²⁺]i elevation that was absent from the DIA 40^oC or other conditions. Thus, no significant differences were found among DIA 40^oC, DIA 30^oC and CONT 30^oC. TRPV1 protein expression was decreased by 42.0% in DIA compared with CONT (P<0.05) and, unlike CONT, heat stress did not increase TRPV1 phosphorylation. In conclusion, diabetes suppresses TRPV1 protein expression and function and inhibits the elevated myocyte [Ca²⁺]i evoked normally by heat stress. These results suggest that capsaicin or other therapeutic strategies to increase Ca²⁺ accumulation via TRPV1 might be more effective than hyperthermic therapy for Type I diabetic patients.

中文翻译：

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I 型糖尿病抑制大鼠骨骼肌中通常由热应激引起的细胞内钙离子增加


热应激通过其对肌肉细胞内 Ca ²⁺浓度 ([Ca ²⁺ ]i) 的影响，已被用作 1 型糖尿病引起的肌肉萎缩的假定治疗对策。使用体内肌肉准备，我们测试了以下假设：I 型糖尿病大鼠肌肉 Ca ²⁺稳态受损是由于 TRPV1 介导的热应激耐受性减弱所致。将雄性 Wistar 大鼠分配至 4 组中的一组：1.对照 30 ^o C (CONT 30 ^o C)、2.CONT 40 ^o C、3.糖尿病 30 ^o C (DIA 30 ^o C)、4.DIA 40 ^o C选择 40 ^o C 是因为它刚好超过 TRPV1 激活阈值。将斜方肌在体内取出并装载荧光Ca ²⁺探针Fura-2AM。使用应用于腹侧肌肉表面的校准热源，在保持在所需温度的静止肌肉中使用荧光显微镜在20分钟内估计[Ca ²⁺ ]i。采用蛋白质印迹法测定斜方肌中 TRPV1 的蛋白表达水平。热应激 20 分钟后，CONT 40 ^o C 条件引起 12.3% [Ca ²⁺ ]i 升高，这是 DIA 40 ^o C 或其他条件所不存在的。因此，DIA 40 ^o C、DIA 30 ^o C 和 CONT 30 ^o C 之间没有发现显着差异。与 CONT 相比，DIA 中 TRPV1 蛋白表达降低了 42.0%（P<0 id=185>2+ ]i 正常诱发）通过热应激。 这些结果表明，对于 I 型糖尿病患者，辣椒素或其他通过 TRPV1 增加 Ca ²⁺积累的治疗策略可能比热疗更有效。