Vitamin D protects pancreatic beta cells in type 2 diabetes.

Chronic inflammation is a principal driver of many of the pathological processes that accompany type 2 diabetes, a metabolic disorder characterized by hyperglycemia (high blood glucose) and subsequent pancreatic beta cell dysfunction. Findings from a recent study suggest that vitamin D blocks activation of the NLRP3 inflammasome, preventing inflammation-driven impairment of pancreatic beta cells.

The NLRP3 inflammasome is a large, intracellular complex that plays critical roles in immune function. Its activation triggers the release of the proinflammatory proteins interleukin (IL)-1 beta and IL-18, promoting inflammation and cell death. People who have type 2 diabetes exhibit upregulated NLRP3 inflammasome activation. However, AMP-activated protein kinase (AMPK), an enzyme that participates in metabolic regulation, blocks NLRP3 activation.

The investigators conducted a three-part study. First, they evaluated the vitamin D status of 399 adults with type 2 diabetes and 78 healthy adults. There was no significant difference in vitamin D status between the two groups. Although males tended to have higher vitamin D concentrations than females, vitamin D deficiency was common among both sexes, with approximately 80 percent of males deficient and 91 percent of females deficient. The investigators then assessed the participants' beta cell function following a meal. They found that higher vitamin D concentrations were associated with greater beta cell function, but this correlation was seen in males only.

In a second experiment, the investigators fed rats either a normal diet or a high-glucose diet (designed to induce beta cell dysfunction) for five weeks. They supplemented half of the rats in both diet groups with vitamin D. At the end of five weeks, they found that among rats that ate the high-glucose diet, those that received vitamin D had lower blood glucose levels than those that did not. The rats that received vitamin D also had greater insulin secretion – an indicator of healthy beta cell function.

Finally, they conducted an in vitro experiment to evaluate the effects of vitamin D on INS1e cells, a well-established model for studies of pancreatic islet beta cell function. They found that vitamin D inhibited hyperglycemia-induced NLRP3 activation and IL-1 beta production, leading to lower levels of inflammation. Further investigation revealed that vitamin D upregulated AMPK production in the cells, which likely contributed to the reduction of inflammation.

These findings suggest that vitamin D inhibits NLRP3 activation via enhanced AMPK production, thereby reducing inflammation due to high blood sugar in mice with type 2 diabetes. Learn more about the beneficial effects of vitamin D in our overview article.

• Link to study abstract.