Pathophysiology & Molecular Pharmacology
The laboratories in this section aim to elucidate pathophysiologic mechanisms in type 2 diabetes, including insulin resistance and β-cell dysfunction, and to exploit this knowledge to create new and better treatments.
Studies conducted by members of the section identified inflammation as both a pathological mediator in insulin resistance and a potential target for its reversal. Investigators practice both bench to bedside and bedside to bench approaches in most aspects of their research. From the clinical perspective, these studies use a form of the anti-inflammatory drug salicylate (salsalate) to treat patients with type 2 diabetes, impaired glucose tolerance, or cardiovascular disease.
These studies are being conducted in collaboration with Allison Goldfine, Joslin’s head of Clinical Research. Parallel basic science studies are being conducted in order to determine how salicylate lowers blood glucose and protects against risk for atherosclerosis.
Several of these have pointed to new roles for the immune system in the pathogenesis of type 2 diabetes. Other basic studies in the section range from structural biology to epigenetics affected by salicylate and an ongoing collaboration with the Blackwell lab using C. elegans to help define salicylate mechanisms of action.
- Showed for the first time that T lymphocytes, and in particular, regulatory T cells, have heretofore unappreciated roles in adipose tissue inflammation and insulin resistance. Nat Med 2009.
- Showed that a surprisingly high grade inflammation occurs in the remnant adipose tissue of lipodystrophic mice, but this is unrelated to insulin resistance. PNAS 2010.
- The TINSAL-T2D clinical trial shows that salsalate, a pro-drug form of salicylate, improves blood glucose and lipids in patients with type 2 diabetes. Annals Intern Med 2010.