Plasma 25-Hydroxyvitamin D Is Related to Protein Signaling Involved in Glucose Homeostasis in a Tissue-Specific Manner

Abstract

Vitamin D has been suggested to play a role in glucose metabolism. However, previous findings are contradictory and mechanistic pathways remain unclear. We examined the relationship between plasma 25-hydroxyvitamin D (25(OH)D), insulin sensitivity, and insulin signaling in skeletal muscle and adipose tissue. Seventeen healthy adults (Body mass index: 26 ± 4; Age: 30 ± 12 years) underwent a hyperinsulinemic-euglycemic clamp, and resting skeletal muscle and adipose tissue biopsies. In this cohort, the plasma 25(OH)D concentration was not associated with insulin sensitivity (r = 0.19, p = 0.56). However, higher plasma 25(OH)D concentrations correlated with lower phosphorylation of glycogen synthase kinase-3 (GSK-3) αSer21 and βSer9 in skeletal muscle (r = −0.66, p = 0.015 and r = −0.53, p = 0.06, respectively) and higher GSK-3 αSer21 and βSer9 phosphorylation in adipose tissue (r = 0.82, p < 0.01 and r = 0.62, p = 0.042, respectively). Furthermore, higher plasma 25(OH)D concentrations were associated with greater phosphorylation of both protein kinase-B (AktSer473) (r = 0.78, p < 0.001) and insulin receptor substrate-1 (IRS-1Ser312) (r = 0.71, p = 0.01) in adipose tissue. No associations were found between plasma 25(OH)D concentration and IRS-1Tyr612 phosphorylation in skeletal muscle and adipose tissue. The divergent findings between muscle and adipose tissue with regard to the association between 25(OH)D and insulin signaling proteins may suggest a tissue-specific interaction with varying effects on glucose homeostasis. Further research is required to elucidate the physiological relevance of 25(OH)D in each tissue.

Diversity of Vaginal Microbiome in Pregnancy: Deciphering the Obscurity

“…Vitamin D influences the vaginal microbiome by maintaining and strengthening the vaginal epithelium, by inducing expression of LL-37, an antimicrobial peptide, and most importantly, by inducing the insulin synthesis and inactivating the glycogen synthase kinase, that subsequently, stimulates the glycogen synthesis. This glycogen acts as a substrate for Lactobacilli and helps in lowering pH by production of lactic acid and therefore, vitamin D deficiency in a pregnant female can lead to spontaneous PTL ( 85 – 87 ).…”

Phosphorylation-Dependent Inhibition of Akt1

“…In close agreement with our findings, studies in adipocytes found that half-maximal Akt1 cellular signaling activity is achieved when the kinase is 5–22% phosphorylated [ 13 ]. In studies of human tumors [ 12 , 13 , 14 , 15 ] and in clinical diagnostic settings [ 14 , 15 ], the phosphorylation status of Akt1 at Ser473 only is often used as a marker or proxy for Akt1 activity. Our work [ 12 ] and work by others [ 16 ] found that phosphorylation of Thr308 alone was sufficient for maximal Akt1 signal prorogation in cells.…”

Vitamin D Supplementation and Non-Alcoholic Fatty Liver Disease: Present and Future

“…Under experimental conditions, vitamin D has been shown to significantly inhibit the hepatic expression of pro-fibrotic mediators such as platelet-derived growth factor (PDGF) and transforming growth factor β (TGF-β) [ 7 , 9 ] and to suppress the expression of collagen, α-smooth muscle actin and tissue inhibitors of metalloproteinase-1; however, its protective action against fibrosis was ineffective once overt hepatic cirrhosis was established [ 9 ]. Furthermore, vitamin D has been proposed as an effective modulator of insulin sensitivity in several experimental models [ 11 , 12 , 13 ] and epidemiological data show the existence of a tight correlation between low circulating vitamin D levels and the presence of obesity [ 14 ], T2D [ 15 ] and insulin resistance-related conditions [ 16 , 17 ].…”