Synergistic actions of vitamin D and metformin on skeletal muscles and insulin resistance of type 2 diabetic rats

J Cell Physiol. 2018 Aug;233(8):5768-5779. doi: 10.1002/jcp.26300. Epub 2018 Feb 28.


Diabetes Mellitus is a chronic generalized disorder due to insulin insufficiency or resistance. Skeletal muscles represent one of the most important target organs that is affected by insulin signaling. The aim of the current work was to investigate the effect of metformin versus vitamin D (and also simultaneous administration) therapy in type 2 diabetic (T2D) rats on the state of the muscle and insulin sensitivity. Thirty six male rats constituted the animal model and have been divided into five groups: control, Diabetic, Diabetic + Metformin, Diabetic + Vitamin D, Diabetic + Metformin + Vitamin D. Blood samples were taken for biochemical measurements of serum calcium, interleukin-6 (IL-6), Triglycerides (TG), glucose, insulin, and calculation of HOMA-IR, and then rats were sacrificed, dissected for removal of gastrocnemius muscle that is used for both biochemical, histopathological and electron microscopy examination. Oral administration of vitamin D alone or in combination with metformin improved insulin sensitivity in skeletal muscles, and sustained the metabolic complications along with muscle atrophy and inflammation in T2D rats. We demonstrated super-beneficial action on insulin resistance of additional vitamin D therapy in T2DM rats that were insufficiently controlled by metformin alone.

Keywords: diabetes; metformin; skeletal muscles; vitamin D.

MeSH terms

  • Animals
  • Blood Glucose / drug effects
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Synergism
  • Hypoglycemic Agents / therapeutic use*
  • Insulin Resistance / physiology*
  • Male
  • Metformin / therapeutic use*
  • Muscle, Skeletal / metabolism*
  • Muscular Atrophy / drug therapy
  • Muscular Atrophy / prevention & control
  • Rats
  • Vitamin D / therapeutic use*


  • Blood Glucose
  • Hypoglycemic Agents
  • Vitamin D
  • Metformin