Sammut Mitchell J, McBey David P, Sayal Amit P, Melling C W James
School of Kinesiology, Faculty of Health Sciences, Western University, London, ON, Canada.
Department of Physiology & Pharmacology, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada.
J Diabetes Res. 2024 Feb 22;2024:5549762. doi: 10.1155/2024/5549762. eCollection 2024.
The etiology of insulin resistance (IR) development in type 1 diabetes mellitus (T1DM) remains unclear; however, impaired skeletal muscle metabolism may play a role. While IR development has been established in male T1DM rodents, female rodents have yet to be examined in this context. Resistance exercise training (RT) has been shown to improve IR and is associated with a lower risk of hypoglycemia onset in T1DM compared to aerobic exercise. The purpose of this study was to investigate the effects of RT on IR development in female T1DM rodents. Forty Sprague Dawley eight-week-old female rats were divided into four groups: control sedentary (CS; = 10), control trained (CT; = 10), T1DM sedentary (DS; = 10), and T1DM trained (DT; = 10). Multiple low-dose streptozotocin injections were used to induce T1DM. Blood glucose levels were maintained in the 4-9 mmol/l range with intensive insulin therapy. CT and DT underwent weighted ladder climbing 5 days/week for six weeks. Intravenous glucose tolerance tests (IVGTT) were conducted on all animals following the six-week period. Results demonstrate that DS animals exhibited significantly increased weekly blood glucose measures compared to all groups including DT ( < 0.0001), despite similar insulin dosage levels. This was concomitant with a significant increase in insulin-adjusted area under the curve following IVGTT in DS ( < 0.05), indicative of a reduction in insulin sensitivity. Both DT and DS exhibited greater serum insulin concentrations compared to CT and CS ( < 0.05). DS animals also exhibited significantly greater glycogen content in white gastrocnemius muscle compared to CS and DT ( < 0.05), whereas DT and DS animals exhibited greater p-Akt: Akt ratio in the white vastus lateralis muscle and citrate synthase activity in the red vastus lateralis muscle compared to CS and CT ( < 0.05). These results indicate that female rodents with T1DM develop poor glycemic control and IR which can be attenuated with RT, possibly related to differences in intramyocellular glycogen content.
1型糖尿病（T1DM）中胰岛素抵抗（IR）发生的病因仍不清楚；然而，骨骼肌代谢受损可能起了一定作用。虽然在雄性T1DM啮齿动物中已证实存在IR的发生，但雌性啮齿动物在这方面尚未得到研究。与有氧运动相比，抗阻运动训练（RT）已被证明可改善IR，并与T1DM中低血糖发作风险较低相关。本研究的目的是调查RT对雌性T1DM啮齿动物IR发生的影响。将40只8周龄的斯普拉格-道利雌性大鼠分为四组：对照久坐组（CS；n = 10）、对照训练组（CT；n = 10）、T1DM久坐组（DS；n = 10）和T1DM训练组（DT；n = 10）。采用多次低剂量链脲佐菌素注射诱导T1DM。通过强化胰岛素治疗将血糖水平维持在4 - 9 mmol/l范围内。CT组和DT组每周进行5天的负重爬梯训练，持续6周。六周后对所有动物进行静脉葡萄糖耐量试验（IVGTT）。结果表明，尽管胰岛素剂量水平相似，但与包括DT组在内的所有组相比，DS组动物每周的血糖测量值显著升高（P < 0.0001）。这与DS组IVGTT后胰岛素调整曲线下面积的显著增加相伴（P < 0.05），表明胰岛素敏感性降低。与CT组和CS组相比，DT组和DS组的血清胰岛素浓度更高（P < 0.05）。与CS组和DT组相比，DS组动物的白色腓肠肌糖原含量也显著更高（P < 0.05），而与CS组和CT组相比，DT组和DS组动物的股外侧肌白色肌肉中p - Akt : Akt比值更高，股外侧肌红色肌肉中的柠檬酸合酶活性更高（P < 0.05）。这些结果表明，患有T1DM的雌性啮齿动物血糖控制不佳且存在IR，而RT可使其减轻，这可能与肌细胞内糖原含量的差异有关。
