Allomyrina dichotoma larva extract attenuates free fatty acid-induced lipotoxicity in pancreatic beta cells

Kyong Kim; Min-Kyu Kwak; Gong-Deuk Bae; Eun-Young Park; Dong-Jae Baek; Chul-Young Kim; Se-Eun Jang; Hee-Sook Jun; Yoon Sin Oh

doi:10.4162/nrp.2021.15.3.294

Allomyrina dichotoma larva extract attenuates free fatty acid-induced lipotoxicity in pancreatic beta cells

Nutr Res Pract. 2021 Jun;15(3):294-308. doi: 10.4162/nrp.2021.15.3.294. Epub 2021 Jan 15.

Authors

Kyong Kim¹, Min-Kyu Kwak¹, Gong-Deuk Bae², Eun-Young Park³, Dong-Jae Baek³, Chul-Young Kim⁴, Se-Eun Jang¹, Hee-Sook Jun⁵, Yoon Sin Oh¹

Affiliations

¹ Department of Food Nutrition, College of Bio Convergence, Eulji University, Seongnam 13135, Korea.
² Institute of Lee Gil Ya Cancer and Diabetes, Department of Molecular Medicine, Gachon University, Incheon 21999, Korea.
³ College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Muan 58554, Korea.
⁴ College of Pharmacy, Hanyang University, Ansan 15588, Korea.
⁵ College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, Incheon 21936, Korea.

Abstract

Backgroud/objectives: Allomyrina dichotoma larva (ADL), one of the many edible insects recognized as future food resources, has a range of pharmacological activities. In a previous study, an ADL extract (ADLE) reduced the hepatic insulin resistance of high-fat diet (HFD)-induced diabetic mice. On the other hand, the associated molecular mechanisms underlying pancreatic beta-cell dysfunction remain unclear. This study examined the effects of ADLE on palmitate-induced lipotoxicity in a beta cell line of a rat origin, INS-1 cells.

Materials/methods: ADLE was administered to high-fat diet treated mice. The expression of apoptosis-related molecules was measured by Western blotting, and reactive oxidative stress generation and nitric oxide production were measured by DCH-DA fluorescence and a Griess assay, respectively.

Results: The administration of ADLE to HFD-induced diabetic mice reduced the hyperplasia, 4-hydroxynonenal levels, and the number of apoptotic cells while improving the insulin levels compared to the HFD group. Treatment of INS-1 cells with palmitate reduced insulin secretion, which was attenuated by the ADLE treatment. Furthermore, the ADLE treatment prevented palmitate-induced cell death in INS-1 cells and isolated islets by reducing the apoptotic signaling molecules, including cleaved caspase-3 and PARP, and the Bax/Bcl2 ratio. ADLE also reduced the levels of reactive oxygen species generation, lipid accumulation, and nitrite production in palmitate-treated INS-1 cells while increasing the ATP levels. This effect corresponded to the decreased expression of inducible nitric oxide synthase (iNOS) mRNA and protein.

Conclusions: ADLE helps prevent lipotoxic beta-cell death in INS-1 cells and HFD-diabetic mice, suggesting that ADLE can be used to prevent or treat beta-cell damage in glucose intolerance during the development of diabetes.

Keywords: Diabetes mellitus; apoptosis; insulin-secreting cells; nitric oxide; oxidative stress.