Introduction: Type 2 diabetes mellitus (T2DM) is a growing health problem. Despite inducing insulin resistance in many circumstances, growth hormone (GH) has been studied as a treatment for T2DM in both humans and mice. Many of the effects of GH are mediated via insulin-like growth factor-1 (IGF-1). Skeletal muscle is an important mediator of insulin resistance and blood glucose uptake. GH may cause a shift toward a slower fiber type profile in skeletal muscle, which may be associated with greater glucose uptake.
Overall Goal: To examine the effects of administration of GH, IGF-1, or both on the muscle fiber type profile and muscle fiber cross-sectional area in diabetic mice.
Methods: C57BL/6J mice were split into five groups as follows: Control (low-fat diet + PBS; n=10), DM (high-fat diet + PBS; n=10), GH (high-fat diet + GH; n=10), IGF-1 (high-fat diet + IGF-1; n=10), Combo (high-fat diet + GH and IGF-1; n=9). Mice were on their respective diets for 16 weeks followed by 3 weeks of hormone or PBS injections. The high-fat diet has previously been shown to induce type 2 diabetes. At the end of the injection period, the mice were sacrificed and the triceps surae muscle group (soleus, plantaris, and gastrocnemius muscles) was removed and weighed. Muscle fiber type composition was determined using myosin ATPase histochemistry and immunohistochemistry and muscle fiber cross-sectional area was analyzed.
Results: Triceps surae mass was greater in the GH and Combo groups compared to the Control, DM, and IGF-1 groups. The DM group had a greater muscle CSA across muscle fiber types in all muscle groups, but no difference in muscle fiber type profile compared to the Control group. The GH, IGF-1, and Combo groups demonstrated a shift toward IIA fibers in the soleus muscle with decreased proportions of type I and/or type IIAD fibers. There were few significant changes in fiber type composition in the plantaris or gastrocnemius muscles. GH increased muscle fiber CSA across fast fiber subtypes, while IGF-1 preferentially increased CSA in slower fiber types of each respective muscle. Combo treatment yielded intermediate results.
Conclusions: Type 2 diabetes in mice increased muscle fiber CSA, but did not affect the fiber type profile of the triceps surae muscle group. GH administration resulted in significant muscle hypertrophy, while IGF-1 yielded a less robust hypertrophic response. GH administration to diabetic mice caused a shift toward type IIA fibers in the soleus with a concomitant decrease in type I and IIAD fibers, while IGF-1 caused a shift toward IIA fibers with a concomitant decrease in IIAD fibers. GH preferentially increased muscle fiber CSA in fast fiber types while IGF-1 increased muscle fiber CSA in the slower fiber types of each respective muscle.