Endocrinology and Metabolism

Case Report

Obesity and Metabolism
Recurrent Insulin Autoimmune Syndrome Caused by α-Lipoic Acid in Type 2 Diabetes: Sang Mook Bae, Myoung Nam Bae, Eun Young Kim, Il Kyu Kim, Min Woo Seo, Jin Kyeong Shin, Sung Rae Cho, Gui Hwa Jeong; Endocrinol Metab. 2013;28(4):326-330. Published online December 12, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.4.326

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Insulin autoimmune syndrome (IAS) is characterized by spontaneous hypoglycemia caused by insulin autoantibodies in the absence of exogenous insulin administration. Some drugs containing sulfhydryl compounds are known to initiate the onset of IAS. A 67-year-old female who had diabetes for 5 years visited the outpatient clinic at our institution due to diabetic peripheral polyneuropathy. She was prescribed α-lipoic acid (ALA), which contains two sulfur atoms. Two weeks later, she complained of recurrent hypoglycemic symptoms. We detected a high level of insulin and high titers of insulin autoantibodies. Her human leukocyte antigen (HLA) genotype included the DRB1*0406 allele, which indicates a high level of susceptibility to IAS. She was treated with prednisolone. After this episode, she experienced two more hypoglycemic events after taking ALA for diabetic neuropathy in other hospitals. As ALA can be used to treat diabetic peripheral polyneuropathy, physician discretion is advised based on the possibility of IAS due to ALA in diabetic patients.

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Original Articles

Effects of Alpha-lipoic Acid on SREBP-1c Expression in HepG2 Cells.: Tae Sung Yun, Ae Kyung Min, Nam Kyung Kim, Mi Kyung Kim, Ho Chan Cho, Hye Soon Kim, Jae Seok Hwang, Seong Yeol Ryu, Keun Gyu Park, In Kyu Lee; J Korean Endocr Soc. 2008;23(1):27-34. Published online February 1, 2008; DOI: https://doi.org/10.3803/jkes.2008.23.1.27

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Abstract PDF

BACKGROUND
Non-alcoholic fatty liver disease is common in patients with insulin resistance. Sterol regulatory element binding protein-1c (SREBP-1c) is a member of a family of transcription factors that have been recognized as key regulators for lipid accumulation in the liver that activate enzymes involved in the fatty acid biosynthetic pathway. This study was designed to evaluate whether alpha-lipoic acid (ALA) inhibits insulin-stimulated SREBP-1c expression. METHODS: We investigated the effects of ALA on insulin-stimulated SREBP-1c expression in a human hepatoma cell line (HepG2 cells) using Northern and Western blot analysis. We also examined the effect of ALA on the promoter activity of the SREBP-1c gene to examine whether ALA can affect SREBP-1c expression at the transcriptional level. To discern the mechanism by which ALA inhibits SREBP-1c expression, we examined the role of AMP-activated protein kinase (AMPK). RESULTS: Insulin increased the expression of SREBP-1c mRNA and protein in HepG2 cells in a dose depended manner. Co-treatment with ALA inhibited the insulin increased SREBP-1c expression in a dose-dependent manner. ALA also inhibited insulin-stimulated activation of the SREBP-1c promoter activity, indicating that ALA inhibited SREBP-1c expression at the transcriptional level. ALA increased phosphorylation of AMPK in HepG2 cells. Inhibition of the AMPK activity by compound C markedly reversed the inhibitory effects of ALA for insulin-stimulated SREBP-1c expression. These results suggest that ALA-induced suppression of SREBP-1c expression is at least in part mediated via AMPK activation. CONCLUSION: The present study suggests that ALA has an inhibitory effect on insulin-stimulated SREBP-1c expression. Therefore, further studies on the effects of ALA on hepatic steatosis in an animal model need to be performed.

Citations

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Effects of an aqueous extract of purple sweet potato on nonalcoholic fatty liver in high fat/cholesterol-fed mice
You Jin Lee, Yoon Kyoung Yang, You Jin Kim, Oran Kwon
Journal of Nutrition and Health.2015; 48(1): 1. CrossRef
Effects of an aqueous extract of purple sweet potato on nonalcoholic fatty liver in high fat/cholesterol-fed mice
You Jin Lee, Yoon Kyoung Yang, You Jin Kim, Oran Kwon
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Effects of alpha-Lipoic Acid on Bone Metabolism in Rats with Low Bone Mass.: Jung Min Koh, Hee Sook Lee, Duk Jae Kim, Ghi Su Kim; J Korean Endocr Soc. 2005;20(5):476-487. Published online October 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.5.476

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Abstract PDF: BACKGROUND
Growing evidence has shown a biochemical link between increased oxidative stress and reduced bone density. In our previous study, alpha-lipoic acid (alpha-LA), a thiol antioxidant, suppressed both osteoclastogenesis and bone resorption, and also prevented TNF-alpha-induced apoptosis of osteoblast lineages. The effects of alpha-LA were investigated on bone metabolism in rats with a low bone mass. METHODS: An ovariectomy (OVX) or Talc injection (inflammation-mediated osteopenia, IMO) was performed in 12 week old female Sprague-Dawley rats. Diets containing either 0.3%, 0.5% or 1.0% alpha-LA were administered to the OVX rats for 16 weeks, and to the IMO rats for 21 days. The bone mineral densities (BMD) of the anterior-posterior lumbar spine and total femur were measured using dual-energy X-ray absorptiometry (Hologic QDR 4500-A), with small animal software. The plasma bone specific alkaline phosphatase activity (BSAP) and urinary free deoxypyridinoline concentration (DPD) were determined using enzyme immunoassay methods. RESULTS: The body weights were significantly decreased in the OVX rats on the diets containing 0.3 and 0.5% alpha-LA than in the OVX control. No significant differences in the BMD at either site were noted between rats administered the diets with or without alpha-LA. However, the administration of various doses of alpha-LA noticeably decreased the level of urinary DPD in both the OVX and IMO rats. High doses of alpha-LA (0.5% and/or 1.0%) also decreased the levels of plasma BSAP in both models. CONCLUSION: Although no increase in BMD was demonstrated by the administration of alpha-LA, these results suggest that alpha-LA suppresses the rates of bone turnover in rats with a low bone mass

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