Combined Teriparatide and Exercise Effects on Diabetic Skeletal Muscle Ultrastructure

The effects of combined teriparatide (TPTD) administration and exercise therapy on diabetic skeletal muscle remain unclear. This study investigated the effects of combined TPTD and treadmill exercise on skeletal muscle and mitochondrial ultrastructure in Akita mice, a model of type 1 diabetes.

Male C57BL/6J-Ins2/J mice were randomly assigned to four groups: control, exercise therapy (EX), TPTD administration, and combined exercise plus TPTD (EXTP) (n=6 each). TPTD (80 μg/kg) was administered subcutaneously three times weekly for six weeks, and treadmill exercise was performed five days/week. Body weight, fasting blood glucose, grip strength, wet muscle weight, muscle fibre cross-sectional area (CSA), mitochondrial and sarcomere ultrastructure, and gene expression were evaluated.

Baseline fasting blood glucose levels were higher in the EXTP group than in the EX and TPTD groups. The EXTP group showed a greater reduction in fasting blood glucose than the other groups and higher wet muscle weight normalised to tibial length than the control group. A-band length and A-band length normalised to tibial length were also higher in the EXTP group. Electron microscopy showed larger subsarcolemmal and intermyofibrillar mitochondrial CSA in the EXTP group. Body weight-normalised grip strength, muscle fibre CSA, myofibril CSA, mitochondrial number, aspect ratio, roundness, and most gene expression levels did not differ among groups.

Combined TPTD administration and exercise therapy may induce structural changes in skeletal muscle and mitochondria under diabetic conditions and may contribute to maintenance or remodelling of skeletal muscle ultrastructure and mitochondrial morphology.