Master of Science (MS)


School of Nutrition and Food Sciences

Document Type



Diabetes is an inflammatory disease associated with hyperglycemia. Chronic exposure of pancreatic â-cells to glucolipotoxicity stimulates a low-grade inflammation associated with the release of pro-inflammatory cytokines such as interleukin-1â (IL-1â). Increased levels of IL-1â can initially lead to decreased insulin secretion and finally â-cell death. Ellagic acid and quercetin have been reported to be anti-inflammatory in several studies. Vitis rotundifolia (muscadine) or Emblica officinalis (amla) are good sources of ellagic acid and quercetin. Ellagic acid or quercetin is bioavailable as is or are metabolized into bioavailable urolithins or isorhamnetin, respectively. The objective of this study was to evaluate the effect of ellagic acid, urolithin A, isorhamnetin, muscadine or amla extracts standardized to their ellagic acid content on glucose-, palmitic acid-, or glucose + palmitic acid-induced IL-1â and insulin secretion. Acid-hydrolyzed and neutralized extracts of muscadine or amla were prepared and the ellagic acid content in the extracts was measured by HPLC. The ellagic acid content in muscadine and amla extracts was 9.4 ± 2.3 mg/g and 19.4 ± 1.5 mg/g, respectively. NIT-1 pancreatic â-cells were incubated with 33.3 mM glucose, 250 µM palmitic acid or 33.3 mM glucose + 250 µM palmitic acid for 24 h followed by addition of 0.01 – 10 µM each of ellagic acid, urolithin A, isorhamnetin, extracts of muscadine or amla standardized to its ellagic acid content followed by additional incubation for 72 h. All incubations were performed at 37oC in a 5% CO2 humidified incubator. IL-1â and insulin were analyzed in the supernatants by ELISA. Glucose, palmitic acid or glucose + palmitic acid up-regulated IL-1â and reduced insulin secretion in NIT-1 cells. Glucose induced more IL-1â secretion than palmitate and reduced insulin secretion than palmitic acid. Ellagic acid, muscadine or amla extracts containing ellagic acid equivalent dose-dependently inhibited IL-1â secretion. Urolithin A or isorhamnetin did not significantly inhibit IL-1â. Ellagic acid, urolithin A, isorhamnetin, or extracts from muscadine or amla dose-dependently increased insulin secretion. Muscadine or amla extracts standardized to their ellagic acid content showed higher stimulation of insulin secretion and IL-1â down-regulation compared to pure ellagic acid. A tentative explanation for this inhibition is the presence of other bioactive compounds in the muscadine or amla extracts. The results of this study show that ellagic acid, muscadine or amla are effective modulators of glucose-, palmitic acid- or glucose+palmitic acid-induced IL-1â secretion and promoters of insulin secretion in â-cells.



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Committee Chair

Losso, Jack N



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Life Sciences Commons