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Sodium fluorocitrate having protective effect on palmitate-induced beta cell death improves hyperglycemia in diabetic db/db mice.

ABSTRACT: Beta cell loss and insulin resistance play roles in the pathogenesis of type 2 diabetes. Elevated levels of free fatty acids in plasma might contribute to the loss of beta cells. The objective of this study was to find a chemical that could protect against palmitate-induced beta cell death and investigate whether such chemical could improve hyperglycemia in mouse model of type 2 diabetes. Sodium fluorocitrate (SFC), an aconitase inhibitor, was found to be strongly and specifically protective against palmitate-induced INS-1 beta cell death. However, the protective effect of SFC on palmitate-induced cell death was not likely to be due to its inhibitory activity for aconitase since inhibition or knockdown of aconitase failed to protect against palmitate-induced cell death. Since SFC inhibited the uptake of palmitate into INS-1 cells, reduced metabolism of fatty acids was thought to be involved in SFC's protective effect. Ten weeks of treatment with SFC in db/db diabetic mice reduced glucose level but remarkably increased insulin level in the plasma. SFC improved impairment of glucose-stimulated insulin release and also reduced the loss of beta cells in db/db mice. Conclusively, SFC possessed protective effect against palmitate-induced lipotoxicity and improved hyperglycemia in mouse model of type 2 diabetes.

SUBMITTER: Jung IR

PROVIDER: S-EPMC5635019 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Sodium fluorocitrate having protective effect on palmitate-induced beta cell death improves hyperglycemia in diabetic db/db mice.

Jung Ik-Rak IR Choi Sung-E SE Hong Seung A SA Hwang Yoonjung Y Kang Yup Y

Scientific reports 20171010 1

Beta cell loss and insulin resistance play roles in the pathogenesis of type 2 diabetes. Elevated levels of free fatty acids in plasma might contribute to the loss of beta cells. The objective of this study was to find a chemical that could protect against palmitate-induced beta cell death and investigate whether such chemical could improve hyperglycemia in mouse model of type 2 diabetes. Sodium fluorocitrate (SFC), an aconitase inhibitor, was found to be strongly and specifically protective aga ...[more]

PMID: 29018279

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Dataset Information

Sodium fluorocitrate having protective effect on palmitate-induced beta cell death improves hyperglycemia in diabetic db/db mice.

Publications

Sodium fluorocitrate having protective effect on palmitate-induced beta cell death improves hyperglycemia in diabetic db/db mice.

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