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Melatonin Ameliorates SGLT2 Inhibitor-Induced Diabetic Ketoacidosis by Inhibiting Lipolysis and Hepatic Ketogenesis in Type 2 Diabetic Mice

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Author(s)
Jae-Hyung ParkIncheol SeoHae-min ShimHochan Cho
Keimyung Author(s)
Park, Jae HyungCho, Ho Chan
Department
Dept. of Physiology (생리학)
Dept. of Internal Medicine (내과학)
Journal Title
Journal of pineal research
Issued Date
2019
Keyword
dapagliflozindiabetic ketoacidosismelatoninSGLT2 inhibitortype 2 diabetes
Abstract
Sodium‐glucose cotransporter‐2 inhibitors (SGLT2i) are effective hypoglycemic agents that can induce glycosuria. However, there are increasing concerns that they might induce diabetic ketoacidosis. This study investigated the effect of melatonin on SGTL2i‐induced ketoacidosis in insulin‐deficient type 2 diabetic (T2D) mice. The SGLT2i dapagliflozin reduced blood glucose level and plasma insulin concentrations in T2D mice, but induced increases in the concentrations of plasma β‐hydroxybutyrate, acetoacetate, and free fatty acid and a decrease in the concentration of plasma bicarbonate, resulting in ketoacidosis. Melatonin inhibited dapagliflozin‐induced ketoacidosis without inducing any change in blood glucose level or plasma insulin concentration. In white adipose tissue, melatonin inhibited lipolysis and downregulated phosphorylation of PKA, HSL, and perilipin‐1. In liver tissue, melatonin suppressed cellular cyclic AMP levels and downregulated phosphorylation of PKA, AMPK, and acetyl‐CoA carboxylase (ACC). In addition, melatonin increased hepatic ACC activity, but decreased hepatic CPT1a activity and acetyl‐CoA content. These effects of melatonin on lipolysis and hepatic ketogenesis were blocked by pretreatment with melatonin receptor antagonist or PKA activator. Collectively, these results suggest that melatonin can ameliorate SGLT2i‐induced ketoacidosis by inhibiting lipolysis and hepatic ketogenesis though cyclic AMP/PKA signaling pathways in T2D mice. Thus, melatonin treatment may offer protection against SGLT2i‐induced ketoacidosis.
Keimyung Author(s)(Kor)
박재형
조호찬
Publisher
School of Medicine (의과대학)
Citation
Jae-Hyung Park et al. (2019). Melatonin Ameliorates SGLT2 Inhibitor-Induced Diabetic Ketoacidosis by Inhibiting Lipolysis and Hepatic Ketogenesis in Type 2 Diabetic Mice. Journal of pineal research, e12623–e12623. doi: 10.1111/jpi.12623
Type
Article
ISSN
1600-079X
Source
https://onlinelibrary.wiley.com/doi/full/10.1111/jpi.12623
DOI
10.1111/jpi.12623
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/42375
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
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