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

Abstract

Resveratrol (RES) and curcumin (CUR) are polyphenols that are found in fruits and turmeric, and possess medicinal properties that are beneficial in various diseases, such as heart disease, cancer, and type 2 diabetes mellitus (T2DM). Results from recent studies have indicated that their therapeutic properties can be attributed to their anti-inflammatory effects. Owing to reports stating that they protect against β-cell dysfunction, we studied their mechanism(s) of action in β-cells. In T2DM, cAMP plays a critical role in glucose- and incretin-stimulated insulin secretion as well as overall pancreatic β-cell health. A potential therapeutic target in the management of T2DM lies in regulating the activity of phosphodiesterases (PDEs), which degrade cAMP. Both RES and CUR have been reported to act as PDE inhibitors in various cell types, but it remains unknown if they do so in pancreatic β-cells. In our current study, we found that both RES (0.1–10 μmol/l) and CUR (1–100 pmol/l)-regulated insulin secretion under glucose-stimulated conditions. Additionally, treating β-cell lines and human islets with these polyphenols led to increased intracellular cAMP levels in a manner similar to 3-isobutyl-1-methylxanthine, a classic PDE inhibitor. When we investigated the effects of RES and CUR on PDEs, we found that treatment significantly downregulated the mRNA expression of most of the 11 PDE isozymes, including PDE3B, PDE8A, and PDE10A, which have been linked previously to regulation of insulin secretion in islets. Furthermore, RES and CUR inhibited PDE activity in a dose-dependent manner in β-cell lines and human islets. Collectively, we demonstrate a novel role for natural-occurring polyphenols as PDE inhibitors that enhance pancreatic β-cell function.

Curcumin treatment enhances the effect of exercise on mitochondrial biogenesis in skeletal muscle by increasing cAMP levels

“…Our results indicated that curcumin and exercise increased the levels of cAMP in Gas (Fig 7A). This result confirms the results of a previous report, which demonstrated the potential of curcumin to increase cAMP levels [34,67]. Identification of cAMP as a target for curcumin in this present study might explain how curcumin mimics some aspects of exercise.…”

A novel curcumin derivative for the treatment of diabetic neuropathy

“…While polypharmacy has traditionally required multiple drugs, there is also potential for a single agent to impact multiple pathways. For example, past studies have demonstrated that curcumin may prevent the onset of diabetes (Rouse et al, 2014) and can also impact neuropathy independent of glycemic control (Sharma et al, 2007). Curcumin, while showing some promising therapeutic properties, has distribution and bioavailability issues that restrict its development as a clinically-viable therapy (Hu et al, 2015).…”

Metformin and soybean-derived bioactive molecules attenuate the expansion of stem cell-like epithelial subpopulation and confer apoptotic sensitivity in human colon cancer cells

“…Nevertheless, the potential interactions of MET and bioactive dietary components with known antitumor activities for CRC prevention and treatment, and specifically in the context of targeting CSC, have not been delineated. The importance of the latter is underscored by recent reports that dietary factors including the soy isoflavone genistein (Gen) (Montales et al 2012;Rahal et al 2013), polyphenolic compounds present in blueberries (Montales et al 2012), curcumin (Kakarala et al 2010), and resveratrol (Kao et al 2009), all of which have been reported to possess anti-metabolic/anti-diabetic properties (Gilbert and Liu 2013;Valsecchi 2013;Yeh et al 2014;Rouse et al 2014), can inhibit expansion of basal stem-like mammary cells with tumorigenic potential.…”