Proteasome inhibitors, including curcumin, improve pancreaticβ-cell function and insulin sensitivity in diabetic mice.
Nutr Diabetes. 2016 ;6:e205. Epub 2016 Apr 25. PMID: 27110686
BACKGROUND: Type 2 diabetes stems from obesity-associated insulin resistance, and in the genetically susceptible, concomitant pancreaticβ-cell failure can occur, which further exacerbates hyperglycemia. Recent work by our group and others has shown that the natural polyphenol curcumin attenuates the development of insulin resistance and hyperglycemia in mouse models of hyperinsulinemic or compensated type 2 diabetes. Although several potential downstream molecular targets of curcumin exist, it is now recognized to be a direct inhibitor of proteasome activity. We now show that curcumin also prevents β-cell failure in a mouse model of uncompensated obesity-related insulin resistance (Lepr(db/db) on the Kaliss background).
RESULTS: In this instance, dietary supplementation with curcumin prevented hyperglycemia, increased insulin production and lean body mass, and prolonged lifespan. In addition, we show that short-term in vivo treatment with low dosages of two molecularly distinct proteasome inhibitors celastrol and epoxomicin reverse hyperglycemia in mice withβ-cell failure by increasing insulin production and insulin sensitivity.
CONCLUSIONS: These studies suggest that proteasome inhibitors may prove useful for patients with diabetes by improving bothβ-cell function and relieving insulin resistance.