Vitamin D may prevent inflammation behind type 2 diabetes and clogged arteries
Researchers from the Washington University School of Medicine looked at the impact of an engineered deletion of the vitamin D receptor on the key immune cells monocytes and macrophages in mice.
Published in the journal Cell Reports, the results suggested this was enough to induce insulin resistance via an accumulation of M2 macrophage – which can play both a negative and positive role in atherosclerosis – in the liver and an increase in the secretion of the cell signalling small protein cytokine and the production of hepatic glucose.
The deletion also lead to increased atherosclerosis, or clogged arteries, by letting fat-laden M2 monocytes adhere, migrate and carry cholesterol into the atherosclerotic plaque and by increasing macrophage cholesterol uptake and reaction (esterification).
When monocytes don’t have vitamin D, they eat up cholesterol and carry it in the bloodstream.
They said this provided new understanding of another way fat could get into blood-vessel walls in patients who were vitamin D deficient and pointed to possible new strategies for people who already suffered from type 2 diabetes and atherosclerosis.
The study published this week forms the basis of the team’s next research project, which will look at whether vitamin D supplementation could help prevent the complications of diabetes and inflammation in humans. The ongoing clinical study will look at isolated monocytes from the blood of patients before and after vitamin D therapy to establish whether any changes had occurred.
"The finding that vitamin D helps regulate glucose metabolism may explain previous epidemiological studies identifying an increased risk of diabetes in patients with vitamin D deficiency," Professor Carlos Bernal-Mizrachi, one of the researchers behind the study, said.
"In our study, inactivation of the vitamin D receptor induced diabetes and atherosclerosis, so normalising vitamin D levels may have the opposite effect."
They found that a bone marrow transplant of vitamin D receptor-expressing cells into the mice improved insulin sensitivity and suppressed atherosclerosis.
Source: Cell Reports
Published online ahead of print, DOI: http://dx.doi.org/10.1016/j.celrep.2015.02.043
“Deletion of Macrophage Vitamin D Receptor Promotes Insulin Resistance and Monocyte Cholesterol Transport to Accelerate Atherosclerosis in Mice”
Authors: J. Oh, A. E. Riek, I. Darwech, K. Funai, J. Shao, K. Chin, O. L. Sierra, G. Carmeliet, R. E. Ostlund Jr, C. Bernal-Mizrachi