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

Abstract

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.

Vit D3 versus L Carnitine Supplement in Alleviating Age-Related Insulin Resistance in A Naturally Aging Rat Model

“…On the contrary, results herein revealed that both VD3 and LC significantly reduced TGs accumulation in the muscle of VD3-aged and LC-aged rats versus aged ones, with more prominent effect of LC in this respect. Our findings were in parallel with previous studies [1,34,43,59] .…”

Relationship between serum 25‐hydroxyvitamin D3levels and severity of chronic periodontitis in type 2 diabetic patients: A cross‐sectional study

“…Vitamin D 3 (VD 3 ) is an essential modulator of calcium and phosphorus metabolism, maintains mucosal barrier homeostasis, and participates in immune regulation . In particular, VD 3 has profound immune‐protective effects in T2DM progression . Recent studies suggest that VD 3 deficiency may play an important role in T2DM and/or CP .…”

“…7,8 In particular, VD 3 has profound immune-protective effects in T2DM progression. 9 Recent studies suggest that VD 3 deficiency may play an important role in T2DM and/or CP. 10,11 However, there is no conclusive evidence pointing to a correlation between VD 3 deficiency and age, glycemia, or circulatory proinflammatory cytokines in T2DCP.…”

Long‐term treatment with metformin in type 2 diabetes and vitaminDlevels:Apost‐hocanalysis of a randomized placebo‐controlled trial

“…Studies on the effects of metformin on vitamin D levels are sparse. Some data suggest a synergic effect of metformin and vitamin D . Only one cross‐sectional study found a negative association between metformin and vitamin D .…”

“…Studies on the effects of metformin on vitamin D levels are sparse. Some data suggest a synergic effect of metformin and vitamin D. 23,24 Only one cross-sectional study found a negative association between metformin and vitamin D. 25 In contrast, 2 other studies found that metformin did not affect treatment of vitamin D deficiency with supplementation of vitamin D. 26,27 Therefore, we investigated whether treatment with metformin vs placebo during 52 months affected vitamin D levels in patients in the Hyperinsulinaemia: the Outcome of its Metabolic Effects (HOME) trial.…”