Host: The Japanese Pharmacological Society
Name : The 96th Annual Meeting of the Japanese Pharmacological Society
Number : 96
Location : [in Japanese]
Date : November 30, 2022 - December 03, 2022
The chronic hyperglycemia in type 2 diabetes causes deterioration of pancreatic β-cell dysfunction
due to decreases in insulin secretory response and β-cell mass. Nobiletin, a citrus flavonoid, has been
reported to improve hyperglycemia and insulin resistance in type 2 diabetic model mice. We
previously showed that nobiletin, a citrus flavonoid, exerts insulinotropic and anti-apoptotic effects
in pancreatic β-cells through the elevation of cAMP levels. In the present study, we investigated
mechanisms for anti-apoptotic effects of nobiletin in INS-1 cells, a rat β-cell line. Endoplasmic
reticulum stress was induced by thapsigargin, tunicamycin, or chronic high glucose exposure. The
expression of apoptosis-related proteins in INS-1 cells was analyzed by Western blotting. Nobiletin
significantly suppressed the elevation of cleaved caspase-3 expression induced by these proapoptotic
stimulations. The expression of thioredoxin interacting protein (TXNIP), a regulator of cellular
oxidative stress, was also suppressed by nobiletin treatment. Nobiletin slightly restored the decrease
in phosphorylated Akt levels induced by thapsigargin or tunicamycin treatment. These results
suggest that nobiletin suppresses apoptosis induced by endoplasmic reticulum stress via the
degradation of TXNIP, which might be mediated by Akt.
