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- Title
Prevention of Lipotoxicity in Pancreatic Islets with Gammahydroxybutyrate.
- Authors
Yung, Justin Hou Ming; Yeung, Lucy Shu Nga; Ivovic, Aleksandar; Tan, Yao Fang; Jentz, Emelien Mariella; Batchuluun, Battsetseg; Gohil, Himaben; Wheeler, Michael B.; Joseph, Jamie W.; Giacca, Adria; Mamelak, Mortimer
- Abstract
Oxidative stress caused by the exposure of pancreatic ß-cells to high levels of fatty acids impairs insulin secretion. This lipotoxicity is thought to play an important role in ß-cell failure in type 2 diabetes and can be prevented by antioxidants. Gamma-hydroxybutyrate (GHB), an endogenous antioxidant and energy source, has previously been shown to protect mice from streptozotocin and alloxan-induced diabetes; both compounds are generators of oxidative stress and yield models of type-1 diabetes. We sought to determine whether GHB could protect mouse islets from lipotoxicity caused by palmitate, a model relevant to type 2 diabetes. We found that GHB prevented the generation of palmitate-induced reactive oxygen species and the associated lipotoxic inhibition of glucose-stimulated insulin secretion while increasing the NADPH/NADP+ ratio. GHB may owe its antioxidant and insulin secretory effects to the formation of NADPH.
- Subjects
ISLANDS of Langerhans; TYPE 2 diabetes; ANIMAL models of diabetes; INSULIN; REACTIVE oxygen species; OXIDATIVE stress
- Publication
Cells (2073-4409), 2022, Vol 11, Issue 3, p545
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells11030545