PT24 - VITAMIN D AS AN AGENT TO MITIGATE INFLAMMATION AND RESTORE GLUCOSE METABOLISM IN INDUCED INSULIN RESISTANT HUMAN ADIPOCYTES

PT24

VITAMIN D AS AN AGENT TO MITIGATE INFLAMMATION AND RESTORE GLUCOSE METABOLISM IN INDUCED INSULIN RESISTANT HUMAN ADIPOCYTES

A. Aladel^1,*, A. Murphy², M. Christian², P. McTernan²

¹Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh , Saudi Arabia, ²Department of Biosciences, School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom

Rationale: Vitamin D regulates metabolic pathways, influencing obesity-mediated insulin resistance and type 2 diabetes mellitus pathology. Yet the mechanisms to mitigate this pathology within human adipocytes are less well known. This study examined the active form of vitamin D, 1,25-dihydroxycholecalciferol (1,25(OH)₂D₃) to mitigate inflammation and insulin resistance from different sources in a human adipocyte cell line. 

Methods: Differentiated human adipocytes (SGBS cells) were treated with TNFα (5ng/mL) or high glucose (h-Glc: 25mM) in combination with high insulin (h-Ins: 100nM) for 24hr, to induce inflammation and insulin resistance, with/without a 24hr pre-treatment of 1,25(OH)₂D₃ (n=6). Key genes and proteins involved in inflammation and insulin sensitivity were assessed.

Results: 1,25(OH)₂D₃ pre-treatment reduced pro-inflammatory gene expression induced by TNFα and h-Glc/h-Ins by up to 62% and 58%* (p<0.0001) respectively. Similarly, 1,25(OH)₂D₃ pre-treatment of TNFα treated cells improved insulin-stimulated glucose uptake and AKT (protein kinase B) phosphorylation by 48% (p<0.05) and 59% (p<0.05) respectively. 1,25(OH)₂D₃ consistently had more impact in TNFα-treated cells than with h-Glc/h-Ins, explained by a 3.2-fold increase in vitamin D receptor (VDR) gene expression (p<0.0001).

Conclusion: In summary, protection of 1,25(OH)₂D₃ against metabolic dysfunction in human adipocytes, was dependent on the source of dysfunction, suggesting better protection for those with prediabetes compared to T2DM.

Disclosure of Interest: None declared