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Resveratrol and curcumin enhance pancreatic beta-cell function by inhibiting phosphodiesterase activity

Thursday, November 07, 2013 — Poster Session II

12:00 p.m. – 2:00 p.m.

FAES Academic Center (Upper-Level Terrace)

NIA

PHARM-8

Authors

  • M.D. Rouse
  • J.M. Egan

Abstract

Resveratrol and curcumin are natural polyphenols found in fruits and turmeric respectively which have been reported to ameliorate various diseases, including type 2 diabetes. In type 2 diabetes, cyclic adenosine-3’,5’-monophosphate (cAMP) plays a critical role in glucose- and incretin- stimulated insulin secretion as well as pancreatic beta-cell function. A potential therapeutic target in the management of type 2 diabetes lies in regulating the activity of phosphodiesterases (PDE), which degrade cAMP. Recent evidence suggests that both resveratrol and curcumin may act as PDE inhibitors, but it remains unclear if they do so in beta-cells. Therefore, we hypothesized that these natural polyphenols would inhibit PDE activity, thus elevating cAMP production and downstream insulin secretion coupling in beta-cells. In our current study, we found both resveratrol (0.1 – 10 uM) and curcumin (1 – 100 pM) increased intracellular cAMP levels as well as insulin secretion similarly to IBMX, a classic PDE inhibitor. Furthermore, these polyphenols were able to downregulate mRNA expression of a majority of the 11 PDE isozymes, including PDE3B, 8A, and 10A, which have been linked previously with regulating insulin secretion in rodent islets. Collectively, we demonstrate a novel role for natural polyphenols as PDE inhibitors that enhance pancreatic beta-cell function.

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