Skeletal muscle myosin heavy chain expression and 3D capillary network changes in streptozotocin-induced diabetic female mice

Abstract

Although the effect of type 1 diabetes (T1DM) on the histological phenotype of skeletal muscle, especially capillarisation, remains poorly understood, this study sought to elucidate the changes in skeletal muscle myosin heavy chain (MyHC) fibres and 3D capillary network characteristics in T1DM-induced mice. Female C57BL/6J-OlaHsd mice were categorized into streptozotocin (STZ)-induced diabetic (n = 12) and age-matched non-diabetic controls (n = 12). The muscle fibre phenotype of the soleus, gluteus maximus, and gastrocnemius muscles was determined by the expression of MyHC isoforms. In contrast, the capillaries of the gluteus maximus were assessed using immunofluorescence staining, confocal laser microscopy, and 3D image analysis. STZ-induced diabetic mice showcased elevated glucose levels, reduced body weight, and prolonged thermal latency, verifying the T1DM phenotype. In both T1DM and non-diabetic mice, the gluteus maximus and gastrocnemius muscles predominantly displayed fast-twitch type 2b fibres, with no significant differences noted. However, the soleus muscle in non-diabetic mice had a greater proportion of type 2a fibres and comparable type 1 fibre densities (26.2 ± 14.6 % vs. 21.9 ± 13.5 %) relative to diabetic mice. T1DM mice showed reduced fibre diameters (P = 0.026), and the 3D capillary network analysis indicated a higher capillary length per muscle volume in the gluteus maximus than controls (P < 0.05). T1DM instigated notable changes in skeletal muscle, such as MyHC fibre type shifts, diminished fibre diameters, and augmented relative capillarisation, potentially attributed to muscle fibre atrophy. Our results underscore the precision of the 3D analytical technique in delineating skeletal muscle capillary architecture and advise caution when interpreting 2D data for capillary changes in T1DM.