Type II Diabetes (T2DM) and obesity's link to the capsaicin receptor, TRPV1

Type II Diabetes Mellitus (T2DM), Obesity, TRPV1, and capsaicin (see last paragraph for a summary of the hypothesized link between these if you don’t feel like reading) –

T2DM and obesity usually go hand in hand, and both diseases augment the other. Recent evidence that both are inflammatory disorders has come about, and will be summarized here along with the possible roles of capsaicin and TRPV1. First, two common treatments for T2DM, rosiglitazone and pioglitazone possess anti-inflammatory activity – treatment of these drugs decreases CRP, a blood marker of low level inflammation, and blood glucose concurrently.

Lots of people claim that eating lots of hot peppers helps you lose weight. A study showed the same thing, 80,000 SHU capsaicin capsules decreased energy intake by ~10%, and increased satiety in volunteers (Westerterp-Plantenga et al., 2005). Capsaicin has been shown to directly activate capsase-3, a mediator of apoptosis, which caused decreased growth of adipocytes – fat cells.

Another marker of inflammation, CGRP is known to increase with age, and can be correlated with T2DM. Since a major source of CGRP is TRPV1 expressing nerves, it is quite possible that killing these nerves with capsaicin could decrease CGRP and the associated risk for insulin resistance in T2DM. Insulin sensitizes TRPV1 expressing neurons, making it more likely that they will release neuropeptides like CGRP and substance P (SP). In the pancreas, CGRP decreases release of insulin, and substance P mediates inflammation of beta islet cells. Killing these neurons prevents aging associated insulin resistance in mice (Melnyk et al., 1995), and improves glucose tolerance in rats made diabetic by chemical treatment (Guillot et al. 1996).

The following hypothesis was proposed for the beneficial effects of TRPV1 agonists (capsaicin) and perhaps antagonists (capsazepine) by Suri and Szallasi in a review article from 2007 in Cell-Opinion. TRPV1 is activated by many components of “inflammatory soup” and T2DM pathogenesis involves low levels of chronic inflammation. If these two premises are true, then TRPV1 expressing nerves would be constitutively more active, thereby releasing more of the inflammatory peptide CGRP. CGRP promotes insulin resistance, which is a hallmark of T2DM. More inflammation means more activation of TRPV1, making it a vicious cycle of inflammation and insulin resistance.