T1DM, Diabetes, TRPV1 and Capsaicin - Prevention

Type 1 Diabetes Mellitus (T1DM) and TRPV1, capsaicin –

T1DM is an autoimmune disease (body’s own immune system killing the body’s cells), which occurs when killer T-cells induce insulin producing cells in the pancreas (specifically beta cells in the islets of Langerhans) to kill themselves. This happens when lymph drainage from the pancreas containing a specific beta cell marker activates T-cells, which sets off a chain of inflammatory events which involves leukocytes secreting various inflammatory markers which induce apoptosis (cell death) in beta cells.

The exact reason that T-cells suddenly start to become activated by normal lymph drainage is not clear. It may be cow milk, viral infection, vitamin D3, or genetic vulnerability (most likely a mix of the latter with one of the former). What is clear is that once the beta cells are gone, they do not replenish, and the body cannot naturally produce insulin ever again (with the possible exception of pancreatic or beta cell transplantation).

In an article published in Cell, the authors (Razavi et al. 2006) claim a new role of the TRPV1 receptor (never heard of it? It’s a calcium channel, heat sensor, capsaicin receptor, and is present on nerves). Using a mouse model of Type 1 Diabetes Mellitus called non-obese diabetic (NOD), they found that subcutaneous injection of capsaicin in 2 day old pups prevented diabetes in these mice by 80%, and delayed onset in most others. That’s right, I said prevented.

That’s not all, after the group sequenced the trpv1 gene, they found two point mutations, which they hypothesized causes decreased function of the protein. To test this, they did several behavioral experiments on the mice and compared them to control mice, and indeed they found that NOD mice exhibit less biting and scratching and licking of an area injected with capsaicin, and, additionally a decrease in the amount of swelling of the paw in response to capsaicin. This behavioral data suggests that NOD mice’s trpv1 gene is a hypofunctional mutant – that is, it doesn’t work right. In support of this, a different strain of NOD mice with a normal trpv1 gene was protected from diabetes.

However, what makes this all even more confusing, is that mice lacking a trpv1 gene altogether (called ‘knockout’ mice by genetic alteration) are also protected from later development of T1DM. The authors suggest that the nerves innervating islet beta cells in the pancreas need a functioning TRPV1 receptor in order to get feedback on the cells’ microenvironments, and respond accordingly. For instance, nerves which have TRPV1 (also called capsaicin sensitive nerves) secrete substance P in response to heat and capsaicin. It is possible that substance P is needed in the pancreas to thwart the T-cells in their attempt to make the beta cells kill themselves. In support of this, the authors found that substance P injected into the pancreas of newly diabetic NOD mice inhibited T-cell proliferation, and partially reversed hyperglycemia for a time.

This study gives a central and novel role to the TRPV1 receptor in pancreatic inflammation with obvious implications for diabetes. If it could be as simple as to inject a child’s pancreas with capsaicin if they are at risk for diabetes, well that would just be a huge breakthrough.