Endocrinology and Metabolism

Brief Report

Diabetes, obesity and metabolism
Partial Deletion of Perk Improved High-Fat Diet-Induced Glucose Intolerance in Mice: Jooyeop Lee, Min Joo Kim, Seoil Moon, Ji Yoon Lim, Kyong Soo Park, Hye Seung Jung; Endocrinol Metab. 2023;38(6):782-787. Published online November 13, 2023; DOI: https://doi.org/10.3803/EnM.2023.1738

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Abstract PDF Supplementary Material PubReader ePub: Although pancreatic endoplasmic reticulum kinase (PERK) is indispensable to beta cells, low-dose PERK inhibitor improved glucose- stimulated insulin secretion (GSIS) and hyperglycemia in diabetic mice. Current study examined if partial deletion of Perk (Perk^+/-) recapitulated the effects of PERK inhibitor, on the contrary to the complete deletion. Perk^+/- mice and wild-type controls were fed with a high-fat diet (HFD) for 23 weeks. Glucose tolerance was evaluated along with serum insulin levels and islet morphology. Perk^+/- mice on normal chow were comparable to wild-type mice in various metabolic features. HFD-induced obesity was not influenced by Perk reduction; however, HFD-induced glucose intolerance was significantly improved since 15-week HFD. HFD-induced compromises in GSIS were relieved by Perk reduction, accompanied by reductions in phosphorylated PERK and activating transcription factor 4 (ATF4) in the islets. Meanwhile, HFD-induced islet expansion was not significantly affected. In summary, partial deletion of Perk improved glucose tolerance and GSIS impaired by diet-induced obesity, without changes in body weights or islet mass.

Original Article

Diabetes, obesity and metabolism
Triglyceride-Glucose Index Predicts Future Atherosclerotic Cardiovascular Diseases: A 16-Year Follow-up in a Prospective, Community-Dwelling Cohort Study: Joon Ho Moon, Yongkang Kim, Tae Jung Oh, Jae Hoon Moon, Soo Heon Kwak, Kyong Soo Park, Hak Chul Jang, Sung Hee Choi, Nam H. Cho; Endocrinol Metab. 2023;38(4):406-417. Published online August 3, 2023; DOI: https://doi.org/10.3803/EnM.2023.1703

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Background
While the triglyceride-glucose (TyG) index is a measure of insulin resistance, its association with cardiovascular disease (CVD) has not been well elucidated. We evaluated the TyG index for prediction of CVDs in a prospective large communitybased cohort.
Methods
Individuals 40 to 70 years old were prospectively followed for a median 15.6 years. The TyG index was calculated as the Ln [fasting triglycerides (mg/dL)×fasting glucose (mg/dL)/2]. CVDs included any acute myocardial infarction, coronary artery disease or cerebrovascular disease. We used a Cox proportional hazards model to estimate CVD risks according to quartiles of the TyG index and plotted the receiver operating characteristics curve for the incident CVD.
Results
Among 8,511 subjects (age 51.9±8.8 years; 47.5% males), 931 (10.9%) had incident CVDs during the follow-up. After adjustment for age, sex, body mass index, diabetes mellitus, hypertension, total cholesterol, smoking, alcohol, exercise, and C-reactive protein, subjects in the highest TyG quartile had 36% increased risk of incident CVD compared with the lowest TyG quartile (hazard ratio, 1.36; 95% confidence interval, 1.10 to 1.68). Carotid plaque, assessed by ultrasonography was more frequent in subjects in the higher quartile of TyG index (P for trend=0.049 in men and P for trend <0.001 in women). The TyG index had a higher predictive power for CVDs than the homeostasis model assessment of insulin resistance (HOMA-IR) (area under the curve, 0.578 for TyG and 0.543 for HOMA-IR). Adding TyG index on diabetes or hypertension alone gave sounder predictability for CVDs.
Conclusion
The TyG index is independently associated with future CVDs in 16 years of follow-up in large, prospective Korean cohort.

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Construction and validation of a nomogram for predicting diabetes remission at 3 months after bariatric surgery in patients with obesity combined with type 2 diabetes mellitus
Kaisheng Yuan, Bing Wu, Ruiqi Zeng, Fuqing Zhou, Ruixiang Hu, Cunchuan Wang
Diabetes, Obesity and Metabolism.2024; 26(1): 169. CrossRef
Association between the triglyceride glucose index and chronic total coronary occlusion: A cross-sectional study from southwest China
Kaiyong Xiao, Huili Cao, Bin Yang, Zhe Xv, Lian Xiao, Jianping Wang, Shuiqing Ni, Hui Feng, Zhongwei He, Lei Xv, Juan Li, Dongmei Xv
Nutrition, Metabolism and Cardiovascular Diseases.2024; 34(4): 850. CrossRef
The association between TyG and all-cause/non-cardiovascular mortality in general patients with type 2 diabetes mellitus is modified by age: results from the cohort study of NHANES 1999–2018
Younan Yao, Bo Wang, Tian Geng, Jiyan Chen, Wan Chen, Liwen Li
Cardiovascular Diabetology.2024;[Epub] CrossRef
Triglyceride-glucose index predicts type 2 diabetes mellitus more effectively than oral glucose tolerance test-derived insulin sensitivity and secretion markers
Min Jin Lee, Ji Hyun Bae, Ah Reum Khang, Dongwon Yi, Mi Sook Yun, Yang Ho Kang
Diabetes Research and Clinical Practice.2024; 210: 111640. CrossRef
Prognostic value of triglyceride-glucose index for left ventricular remodeling in nondiabetic ST-elevation myocardial infarction patients
Tolga Han Efe, Engin Algül
Biomarkers in Medicine.2024;[Epub] CrossRef
Evaluation of the novel three lipid indices for predicting five- and ten-year incidence of cardiovascular disease: findings from Kerman coronary artery disease risk factors study (KERCADRS)
Alireza Jafari, Hamid Najafipour, Mitra Shadkam, Sina Aminizadeh
Lipids in Health and Disease.2023;[Epub] CrossRef

Review Article

Diabetes
Pathophysiology of Type 2 Diabetes in Koreans: Soo Heon Kwak, Kyong Soo Park; Endocrinol Metab. 2018;33(1):9-16. Published online March 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.1.9

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The pathophysiology of type 2 diabetes is characterized by variable degrees of insulin resistance and impaired insulin secretion. Both genetic and environmental factors serve as etiologic factors. Recent genetic studies have identified at least 83 variants associated with diabetes. A significant number of these loci are thought to be involved in insulin secretion, either through β-cell development or β-cell dysfunction. Environmental factors have changed rapidly during the past half century, and the increased prevalence of obesity and diabetes can be attributed to these changes. Environmental factors may affect epigenetic changes and alter susceptibility to diabetes. A recent epidemiologic study revealed that Korean patients with type 2 diabetes already had impaired insulin secretion and insulin resistance 10 years before the onset of diabetes. Those who developed diabetes showed impaired β-cell compensation with an abrupt decrease in insulin secretion during the last 2 years before diabetes developed. The retrograde trajectory of the disposition index differed according to the baseline subgroups of insulin secretion and insulin sensitivity. We hope that obtaining a more detailed understanding of the perturbations in the major pathophysiologic process of diabetes on the individual level will eventually lead to the implementation of precision medicine and improved patient outcomes.

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Stress-Reducing Psychological Interventions as Adjuvant Therapies for Diabetic Chronic Wounds
Isadora Pombeiro, João Moura, M. Graça Pereira, Eugénia Carvalho
Current Diabetes Reviews.2022;[Epub] CrossRef
Umbilical Cord-Mesenchymal Stem Cell-Conditioned Medium Improves Insulin Resistance in C2C12 Cell
Kyung-Soo Kim, Yeon Kyung Choi, Mi Jin Kim, Jung Wook Hwang, Kyunghoon Min, Sang Youn Jung, Soo-Kyung Kim, Yong-Soo Choi, Yong-Wook Cho
Diabetes & Metabolism Journal.2021; 45(2): 260. CrossRef
Dose-Dependent Effect of Smoking on Risk of Diabetes Remains after Smoking Cessation: A Nationwide Population-Based Cohort Study in Korea
Se Eun Park, Mi Hae Seo, Jung-Hwan Cho, Hyemi Kwon, Yang-Hyun Kim, Kyung-Do Han, Jin-Hyung Jung, Yong-Gyu Park, Eun-Jung Rhee, Won-Young Lee
Diabetes & Metabolism Journal.2021; 45(4): 539. CrossRef
DNA Methylation Changes Associated With Type 2 Diabetes and Diabetic Kidney Disease in an East Asian Population
Hakyung Kim, Jae Hyun Bae, Kyong Soo Park, Joohon Sung, Soo Heon Kwak
The Journal of Clinical Endocrinology & Metabolism.2021; 106(10): e3837. CrossRef
Associations among Obesity Degree, Glycemic Status, and Risk of Heart Failure in 9,720,220 Korean Adults
Eun-Jung Rhee, Hyemi Kwon, Se Eun Park, Kyung-Do Han, Yong-Gyu Park, Yang-Hyun Kim, Won-Young Lee
Diabetes & Metabolism Journal.2020; 44(4): 592. CrossRef
Smoking as a Target for Prevention of Diabetes
Ye Seul Yang, Tae Seo Sohn
Diabetes & Metabolism Journal.2020; 44(3): 402. CrossRef
Clinical characteristics of diabetic ketoacidosis in users and non-users of SGLT2 inhibitors
J.Y. Jeon, S.-K. Kim, K.-S. Kim, S.O. Song, J.-S. Yun, B.-Y. Kim, C.-H. Kim, S.O. Park, S. Hong, D.H. Seo, J.A. Seo, J.H. Noh, D.J. Kim
Diabetes & Metabolism.2019; 45(5): 453. CrossRef
Identifying Pathogenic Variants of Monogenic Diabetes Using Targeted Panel Sequencing in an East Asian Population
Seung Shin Park, Se Song Jang, Chang Ho Ahn, Jung Hee Kim, Hye Seung Jung, Young Min Cho, Young Ah Lee, Choong Ho Shin, Jong Hee Chae, Jae Hyun Kim, Sung Hee Choi, Hak C Jang, Jee Cheol Bae, Jong Cheol Won, Sung-Hoon Kim, Jong-Il Kim, Soo Heon Kwak, Kyong
The Journal of Clinical Endocrinology & Metabolism.2019; 104(9): 4188. CrossRef
Epigenetic Markers and Microbiota/Metabolite-Induced Epigenetic Modifications in the Pathogenesis of Obesity, Metabolic Syndrome, Type 2 Diabetes, and Non-alcoholic Fatty Liver Disease
Daniela Stols-Gonçalves, Luca Schiliró Tristão, Peter Henneman, Max Nieuwdorp
Current Diabetes Reports.2019;[Epub] CrossRef
The cut-off values of surrogate measures for insulin resistance in the Korean population according to the Korean Genome and Epidemiology Study (KOGES)
Bongyoung Kim, Hyun Young Choi, Wonhee Kim, Chiwon Ahn, Juncheol Lee, Jae Guk Kim, Jihoon Kim, Hyungoo Shin, Jae Myung Yu, Shinje Moon, Taulant Muka
PLOS ONE.2018; 13(11): e0206994. CrossRef

Erratum

Erratum: Correction of Figure. Clinical Implications of Various Criteria for the Biochemical Diagnosis of Insulinoma: Chang Ho Ahn, Lee-Kyung Kim, Jie Eun Lee, Chan-Hyeon Jung, Se-Hee Min, Kyong Soo Park, Seong Yeon Kim, Young Min Cho; Endocrinol Metab. 2017;32(2):306. Published online June 23, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.2.306

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Original Articles

Clinical Study
1,5-Anhydro-D-Glucitol Could Reflect Hypoglycemia Risk in Patients with Type 2 Diabetes Receiving Insulin Therapy: Min Kyeong Kim, Hye Seung Jung, Soo Heon Kwak, Young Min Cho, Kyong Soo Park, Seong Yeon Kim; Endocrinol Metab. 2016;31(2):284-291. Published online May 27, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.2.284

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Background

The identification of a marker for hypoglycemia could help patients achieve strict glucose control with a lower risk of hypoglycemia. 1,5-Anhydro-D-glucitol (1,5-AG) reflects postprandial hyperglycemia in patients with well-controlled diabetes, which contributes to glycemic variability. Because glycemic variability is related to hypoglycemia, we aimed to evaluate the value of 1,5-AG as a marker of hypoglycemia.

Methods

We enrolled 18 adults with type 2 diabetes mellitus (T2DM) receiving insulin therapy and assessed the occurrence of hypoglycemia within a 3-month period. We measured 1,5-AG level, performed a survey to score the severity of hypoglycemia, and applied a continuous glucose monitoring system (CGMS).

Results

1,5-AG was significantly lower in the high hypoglycemia-score group compared to the low-score group. Additionally, the duration of insulin treatment was significantly longer in the high-score group. Subsequent analyses were adjusted by the duration of insulin treatment and mean blood glucose, which was closely associated with both 1,5-AG level and hypoglycemia risk. In adjusted correlation analyses, 1,5-AG was negatively correlated with hypoglycemia score, area under the curve at 80 mg/dL, and low blood glucose index during CGMS (P=0.068, P=0.033, and P=0.060, respectively).

Conclusion

1,5-AG level was negatively associated with hypoglycemia score determined by recall and with documented hypoglycemia after adjusting for mean glucose and duration of insulin treatment. As a result, this level could be a marker of the risk of hypoglycemia in patients with well-controlled T2DM receiving insulin therapy.

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Tae Jung Oh, Jie-Eun Lee, Seok Kim, Sooyoung Yoo, Hak Chul Jang
CardioMetabolic Syndrome Journal.2021; 1(1): 88. CrossRef
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Low and exacerbated levels of 1,5-anhydroglucitol are associated with cardiovascular events in patients after first-time elective percutaneous coronary intervention
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Cardiovascular Diabetology.2016;[Epub] CrossRef

Endocrine Research
Thyroid Hormone Regulates the mRNA Expression of Small Heterodimer Partner through Liver Receptor Homolog-1: Hwa Young Ahn, Hwan Hee Kim, Ye An Kim, Min Kim, Jung Hun Ohn, Sung Soo Chung, Yoon-Kwang Lee, Do Joon Park, Kyong Soo Park, David D. Moore, Young Joo Park; Endocrinol Metab. 2015;30(4):584-592. Published online December 31, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.4.584

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Background

Expression of hepatic cholesterol 7α-hydroxylase (CYP7A1) is negatively regulated by orphan nuclear receptor small heterodimer partner (SHP). In this study, we aimed to find whether thyroid hormone regulates SHP expression by modulating the transcriptional activities of liver receptor homolog-1 (LRH-1).

Methods

We injected thyroid hormone (triiodothyronine, T3) to C57BL/6J wild type. RNA was isolated from mouse liver and used for microarray analysis and quantitative real-time polymerase chain reaction (PCR). Human hepatoma cell and primary hepatocytes from mouse liver were used to confirm the effect of T3 in vitro. Promoter assay and electrophoretic mobility-shift assay (EMSA) were also performed using human hepatoma cell line

Results

Initial microarray results indicated that SHP expression is markedly decreased in livers of T3 treated mice. We confirmed that T3 repressed SHP expression in the liver of mice as well as in mouse primary hepatocytes and human hepatoma cells by real-time PCR analysis. LRH-1 increased the promoter activity of SHP; however, this increased activity was markedly decreased after thyroid hormone receptor β/retinoid X receptor α/T3 administration. EMSA revealed that T3 inhibits specific LRH-1 DNA binding.

Conclusion

We found that thyroid hormone regulates the expression of SHP mRNA through interference with the transcription factor, LRH-1.

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Bile acid and receptors: biology and drug discovery for nonalcoholic fatty liver disease
Ting-ying Jiao, Yuan-di Ma, Xiao-zhen Guo, Yun-fei Ye, Cen Xie
Acta Pharmacologica Sinica.2022; 43(5): 1103. CrossRef
Loperamide induces excessive accumulation of bile acids in the liver of mice with different diets
Zili Lei, Hedong Rong, Yanhong Yang, Siping Yu, Tianle Zhang, Lei Chen, Ya Nie, Qi Song, Qing Hu, Jiao Guo
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Pathogenesis of hypothyroidism-induced NAFLD is driven by intra- and extrahepatic mechanisms
Giuseppe Ferrandino, Rachel R. Kaspari, Olga Spadaro, Andrea Reyna-Neyra, Rachel J. Perry, Rebecca Cardone, Richard G. Kibbey, Gerald I. Shulman, Vishwa Deep Dixit, Nancy Carrasco
Proceedings of the National Academy of Sciences.2017;[Epub] CrossRef

Clinical Study
Clinical Characteristics of Subjects with Sulfonylurea-Dependent Type 2 Diabetes: Se Hee Min, Soo Heon Kwak, Young Min Cho, Kyong Soo Park, Hye Seung Jung; Endocrinol Metab. 2015;30(4):509-513. Published online December 31, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.4.509

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Background

Even though several oral anti-diabetic drugs (OAD) with various modes of action are replacing sulfonylurea (SU), some patients seem to be dependent on SU for adequate glycemic control. Therefore, we evaluated the clinical characteristics of such patients.

Methods

We selected the patients with type 2 diabetes who met following criteria from 2009 to 2014 at Seoul National University Hospital: glycated hemoglobin (HbA1c) was maintained below 7.5% for at least 6 months under small dose of SU (glimepiride ≤2 mg/day or equivalent dose); after discontinuation of SU, HbA1c increased ≥1.2% within 3 months or ≥1.5% within 6 months; and after resuming SU, HbA1c reduction was ≥0.8% or reduction of fasting plasma glucose was ≥40 mg/dL within 3 months. Patients with impaired hepatic or renal function, and steroid users were excluded.

Results

Nineteen subjects were enrolled: after averaged 4.8±1.5 months of SU-free period, HbA1c increased from 6.7%±0.4% to 8.8%±0.8% even though adding other OAD such as gliptins. However, HbA1c decreased to 7.4%±0.7% after resuming SU within 2.4±0.8 months. There was no sexual predominance. Despite their old age (67±11 years) and long duration of diabetes (18±10 years), fasting C-peptide was relatively well-reserved (3.9±2.6 ng/mL), and nephropathy was not observed (albumin-creatinine ratio 21.2±16.6 mg/g and estimated glomerular filtration rate 75.8±18.0 mL/min/1.73 m²). Strong family history was also noted (73.7%).

Conclusion

Despite hypoglycemia risk of SU, it seemed indispensable for a subset of patients with regard to insulin secretion. Genetic influences would be evaluated.

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Incident Hepatocellular Carcinoma Risk in Patients Treated with a Sulfonylurea: A Nationwide, Nested, Case-Control Study
Ji-Yeon Lee, Suk-Yong Jang, Chung Mo Nam, Eun Seok Kang
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A genetic variant in GLP1R is associated with response to DPP-4 inhibitors in patients with type 2 diabetes
Eugene Han, Hye Sun Park, Obin Kwon, Eun Yeong Choe, Hye Jin Wang, Yong-ho Lee, Sang-Hak Lee, Chul Hoon Kim, Lee-Kyung Kim, Soo Heon Kwak, Kyong Soo Park, Chul Sik Kim, Eun Seok Kang
Medicine.2016; 95(44): e5155. CrossRef

Case Report

Partial Androgen Insensitivity Syndrome Presenting with Gynecomastia: Sung Won Lee, Dong Shin Kwak, In Sub Jung, Joo Hee Kwak, Jung Hwan Park, Sang Mo Hong, Chang Bum Lee, Yong Soo Park, Dong Sun Kim, Woong Hwan Choi, You Hern Ahn; Endocrinol Metab. 2015;30(2):226-230. Published online June 30, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.2.226

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Abstract PDF PubReader

Gynecomastia is a benign enlargement of the male breast caused by the proliferation of glandular breast tissue. Determining the various causes of gynecomastia such as physiological causes, drugs, systemic diseases, and endocrine disorders is important. Androgen insensitivity syndrome (AIS) is a rare endocrine disorder presenting with gynecomastia and is a disorder of male sexual differentiation caused by mutations within the androgen receptor gene. All individuals with AIS have the 46 XY karyotype, although AIS phenotypes can be classified as mild, partial or complete and can differ among both males and females including ambiguous genitalia or infertility in males. We experienced a case of partial AIS presenting with gynecomastia and identified the androgen receptor gene mutation.

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Clinical outcomes and genotype-phenotype correlations in patients with complete and partial androgen insensitivity syndromes
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Review Article

Obesity and Metabolism
Genetic Studies on Diabetic Microvascular Complications: Focusing on Genome-Wide Association Studies: Soo Heon Kwak, Kyong Soo Park; Endocrinol Metab. 2015;30(2):147-158. Published online June 30, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.2.147

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Diabetes is a common metabolic disorder with a worldwide prevalence of 8.3% and is the leading cause of visual loss, end-stage renal disease and amputation. Recently, genome-wide association studies (GWASs) have identified genetic risk factors for diabetic microvascular complications of retinopathy, nephropathy, and neuropathy. We summarized the recent findings of GWASs on diabetic microvascular complications and highlighted the challenges and our opinion on future directives. Five GWASs were conducted on diabetic retinopathy, nine on nephropathy, and one on neuropathic pain. The majority of recent GWASs were underpowered and heterogeneous in terms of study design, inclusion criteria and phenotype definition. Therefore, few reached the genome-wide significance threshold and the findings were inconsistent across the studies. Recent GWASs provided novel information on genetic risk factors and the possible pathophysiology of diabetic microvascular complications. However, further collaborative efforts to standardize phenotype definition and increase sample size are necessary for successful genetic studies on diabetic microvascular complications.

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World Journal of Diabetes.2023; 14(6): 656. CrossRef
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Qinghua Huang, Dujin Feng, Lianlian Pan, Huan Wang, Yan Wu, Bin Zhong, Jianguang Gong, Huijun Lin, Xianming Fei
PeerJ.2023; 11: e16352. CrossRef
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Original Articles

Obesity and Metabolism
Mitochondrial Complexes I and II Are More Susceptible to Autophagy Deficiency in Mouse β-Cells: Min Joo Kim, Ok Kyong Choi, Kyung Sil Chae, Min Kyeong Kim, Jung Hee Kim, Masaaki Komatsu, Keiji Tanaka, Hakmo Lee, Sung Soo Chung, Soo Heon Kwak, Young Min Cho, Kyong Soo Park, Hye Seung Jung; Endocrinol Metab. 2015;30(1):65-70. Published online March 27, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.1.65

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Background

Damaged mitochondria are removed by autophagy. Therefore, impairment of autophagy induces the accumulation of damaged mitochondria and mitochondrial dysfunction in most mammalian cells. Here, we investigated mitochondrial function and the expression of mitochondrial complexes in autophagy-related 7 (Atg7)-deficient β-cells.

Methods

To evaluate the effect of autophagy deficiency on mitochondrial function in pancreatic β-cells, we isolated islets from Atg7^F/F:RIP-Cre+ mice and wild-type littermates. Oxygen consumption rate and intracellular adenosine 5'-triphosphate (ATP) content were measured. The expression of mitochondrial complex genes in Atg7-deficient islets and in β-TC6 cells transfected with siAtg7 was measured by quantitative real-time polymerase chain reaction.

Results

Baseline oxygen consumption rate of Atg7-deficient islets was significantly lower than that of control islets (P<0.05). Intracellular ATP content of Atg7-deficient islets during glucose stimulation was also significantly lower than that of control islets (P<0.05). By Oxygraph-2k analysis, mitochondrial respiration in Atg7-deficient islets was significantly decreased overall, although state 3 respiration and responses to antimycin A were unaffected. The mRNA levels of mitochondrial complexes I, II, III, and V in Atg7-deficient islets were significantly lower than in control islets (P<0.05). Down-regulation of Atg7 in β-TC6 cells also reduced the expression of complexes I and II, with marginal significance (P<0.1).

Conclusion

Impairment of autophagy in pancreatic β-cells suppressed the expression of some mitochondrial respiratory complexes, and may contribute to mitochondrial dysfunction. Among the complexes, I and II seem to be most vulnerable to autophagy deficiency.

Citations

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Proteomic pathways to metabolic disease and type 2 diabetes in the pancreatic islet
Belinda Yau, Sheyda Naghiloo, Alexis Diaz-Vegas, Austin V. Carr, Julian Van Gerwen, Elise J. Needham, Dillon Jevon, Sing-Young Chen, Kyle L. Hoehn, Amanda E. Brandon, Laurence Macia, Gregory J. Cooney, Michael R. Shortreed, Lloyd M. Smith, Mark P. Keller,
iScience.2021; 24(10): 103099. CrossRef
Natural compound oblongifolin C inhibits autophagic flux, and induces apoptosis and mitochondrial dysfunction in human cholangiocarcinoma QBC939 cells
Aiqing Zhang, Wei He, Huimin Shi, Xiaodan Huang, Guozhong Ji
Molecular Medicine Reports.2016; 14(4): 3179. CrossRef
Autophagy deficiency in β cells blunts incretin-induced suppression of glucagon release from α cells
Min Joo Kim, Ok Kyong Choi, Kyung Sil Chae, Hakmo Lee, Sung Soo Chung, Dong-Sik Ham, Ji-Won Kim, Kun-Ho Yoon, Kyong Soo Park, Hye Seung Jung
Islets.2015; 7(5): e1129096. CrossRef

Obesity and Metabolism
Clinical Implications of Various Criteria for the Biochemical Diagnosis of Insulinoma: Chang Ho Ahn, Lee-Kyung Kim, Jie Eun Lee, Chan-Hyeon Jung, Se-Hee Min, Kyong Soo Park, Seong Yeon Kim, Young Min Cho; Endocrinol Metab. 2014;29(4):498-504. Published online December 29, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.4.498

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Abstract PDF PubReader

Background

Among the various diagnostic criteria for insulinoma, the ratio criteria have been controversial. However, the amended insulin-glucose ratio exhibited excellent diagnostic performance in a recent retrospective cohort study, although it has not yet been validated in other patient cohorts. We examined the diagnostic performance of the current criteria of the Endocrine Society, insulin-glucose ratio, C-peptide-glucose ratio, and amended ratios in terms of differentiating insulinomas.

Methods

We reviewed the medical records of patients who underwent evaluation for hypoglycemia from 2000 to 2013. Fourteen patients with histopathologically confirmed insulinoma and 18 patients without clinical evidence of insulinoma were included. The results of a prolonged fast test were analyzed according to the abovementioned criteria.

Results

Fulfilling all three Endocrine Society criteria-plasma levels of glucose (<3.0 mmol/L), insulin (≥8 pmol/L), and C-peptide (≥0.2 nmol/L)-exhibited 100% sensitivity and 89% specificity. Fulfilling the glucose and C-peptide criteria showed 100% sensitivity and 83% specificity, while fulfilling the glucose and insulin criteria showed 100% sensitivity and 72% specificity. Among the ratio criteria, the insulin-glucose ratio [>24.0 (pmol/L)/(mmol/L)] gave the highest area under the receiver operating characteristic curve, with 93% sensitivity and 94% specificity.

Conclusion

Fulfilling the glucose, insulin, and C-peptide criteria of the Endocrine Society guidelines exhibited the best diagnostic performance for insulinoma. Nonetheless, the insulin-glucose ratio may still have a role in the biochemical diagnosis of insulinoma.

Citations

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Homeostasis Model Assessment of β-Cell Function for Diagnosis of Insulinoma
Kálmán Bódis, Martin Schön, Laura Dauben, Miriam Wilker, Klaus Strassburger, Volker Burkart, Michael Roden, Karsten Müssig
The Journal of Clinical Endocrinology & Metabolism.2024; 109(3): e1125. CrossRef
A novel diagnostic model for insulinoma
Feng Wang, Zhe Yang, XiuBing Chen, Yiling Peng, HaiXing Jiang, ShanYu Qin
Discover Oncology.2022;[Epub] CrossRef
Comparison of the diagnostic accuracy of the current guidelines for detecting insulinoma
Laura Dauben, Marie-Christine Simon, Klaus Strassburger, Volker Burkart, Katharina S Weber, Sven Schinner, Michael Roden, Karsten Müssig
European Journal of Endocrinology.2019; 180(6): 381. CrossRef
EUS-guided lauromacrogol ablation of insulinomas: a novel treatment
Shanyu Qin, Yongru Liu, Hongjian Ning, Lin Tao, Wei Luo, Donghong Lu, Zuojie Luo, Yingfen Qin, Jia Zhou, Junqiang Chen, Haixing Jiang
Scandinavian Journal of Gastroenterology.2018; 53(5): 616. CrossRef
Diagnosis of insulinoma using the ratios of serum concentrations of insulin and C-peptide to glucose during a 5-hour oral glucose tolerance test
Xu Li, Feng Zhang, Haibing Chen, Haoyong Yu, Jian Zhou, Ming Li, Qing Li, Lianxi Li, Jun Yin, Fang Liu, Yuqian Bao, Junfeng Han, Weiping Jia
Endocrine Journal.2017; 64(1): 49. CrossRef
Insulinoma in a 5‐Year‐Old Dexter Cow
C. Binici, S. Plog, O. Kershaw, M. Schmicke, J.H. van der Kolk, K.E. Müller
Journal of Veterinary Internal Medicine.2016; 30(4): 1402. CrossRef
Vague neuroglycopenic complaints camouflage diagnosis of adolescent insulinoma: a case report
Kelsee Halpin, Ryan McDonough, Patria Alba, Jared Halpin, Vivekanand Singh, Yun Yan
International Journal of Pediatric Endocrinology.2016;[Epub] CrossRef
Articles in 'Endocrinology and Metabolism' in 2014
Won-Young Lee
Endocrinology and Metabolism.2015; 30(1): 47. CrossRef

Obesity and Metabolism
A Novel Mutation in the Von Hippel-Lindau Tumor Suppressor Gene Identified in a Patient Presenting with Gestational Diabetes Mellitus: Yun Hyi Ku, Chang Ho Ahn, Chan-Hyeon Jung, Jie Eun Lee, Lee-Kyung Kim, Soo Heon Kwak, Hye Seung Jung, Kyong Soo Park, Young Min Cho; Endocrinol Metab. 2013;28(4):320-325. Published online December 12, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.4.320

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Abstract PDF PubReader

Background

Von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited, multisystemic tumor syndrome caused by mutations in the VHL gene. To date, more than 1,000 germline and somatic mutations of the VHL gene have been reported. We present a novel mutation in the VHL tumor suppressor gene that presented with gestational diabetes mellitus.

Methods

A 30-year-old woman presented with gestational diabetes mellitus. She sequentially showed multiple pancreatic cysts, spinal cord hemangioblastoma, cerebellar hemangioblastoma, and clear cell type renal cell carcinomas. Also, her father and brother had brain hemangioblastomas. Each of the three exons of the VHL gene was individually amplified by polymerase chain reaction and direct sequencing was performed using an ABI 3730 DNA analyzer.

Results

DNA sequence analysis to determine the presence of VHL mutation in her family revealed del291C, a novel frameshift mutation.

Conclusion

We found a novel mutation in the VHL tumor suppressor gene that presented with gestational diabetes mellitus.

Citations

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Diversities of Mechanism in Patients with VHL Syndrome and diabetes: A Report of Two Cases and Literature Review
Yanlei Wang, Zhaoxiang Liu, Wenhui Zhao, Chenxiang Cao, Luqi Xiao, Jianzhong Xiao
Diabetes, Metabolic Syndrome and Obesity.2024; Volume 17: 1611. CrossRef
Retinal hemangioblastoma in a patient with Von Hippel-Lindau disease: A case report and literature review
Yikeng Huang, Weiwen Hu, Xionggao Huang
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Updates on the Role of Molecular Alterations and NOTCH Signalling in the Development of Neuroendocrine Neoplasms
Claudia von Arx, Monica Capozzi, Elena López-Jiménez, Alessandro Ottaiano, Fabiana Tatangelo, Annabella Di Mauro, Guglielmo Nasti, Maria Lina Tornesello, Salvatore Tafuto
Journal of Clinical Medicine.2019; 8(9): 1277. CrossRef
Brief Review of Articles in 'Endocrinology and Metabolism' in 2013
Won-Young Lee
Endocrinology and Metabolism.2014; 29(3): 251. CrossRef

Thyroid
Expression of Thyroid Stimulating Hormone Receptor mRNA in Mouse C2C12 Skeletal Muscle Cells: Jung Hun Ohn, Sun Kyoung Han, Do Joon Park, Kyong Soo Park, Young Joo Park; Endocrinol Metab. 2013;28(2):119-124. Published online June 18, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.2.119

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39 Download
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11 Crossref

Abstract PDF PubReader

Background

We analyzed whether thyroid stimulating hormone receptor (TSH-R) is expressed in a skeletal muscle cell line and if TSH has influence on the differentiation of muscle cells or on the determination of muscle fiber types.

Methods

TSH-R gene expression was detected with nested real-time polymerase chain reaction (RT-PCR) in C2C12, a mouse skeletal muscle cell line. The effect of TSH on myotube differentiation was assessed by microscopic examination of myotube formation and through the measurement of expression of muscle differentiation markers, i.e., myogenin and myoD, and muscle type-specific genes, i.e., MyHC1, MyHC2a, and MyHC2b, with quantitative RT-PCR before and after incubation of C2C12 myotube with TSH.

Results

TSH-R was expressed in the mouse skeletal muscle cell line. However, treatment with TSH had little effect on the differentiation of muscle cells, although the expression of the muscle differention marker myogenin was significantly increased after TSH treatment. Treatment of TSH did not affect the expression of muscle type-specific genes.

Conclusion

TSH-R is expressed in a mouse skeletal muscle cell line, but the role of TSH receptor signaling in skeletal muscle needs further investigation.

Citations

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Shinnosuke Hata, Hiroshi Okada, Megumi Minamida, Junya Hironaka, Yuka Hasegawa, Yuriko Kondo, Hanako Nakajima, Nobuko Kitagawa, Takuro Okamura, Yoshitaka Hashimoto, Takafumi Osaka, Noriyuki Kitagawa, Saori Majima, Takafumi Senmaru, Emi Ushigome, Naoko Nak
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Jun Choul Lee, Byong-Sop Song, Young Mi Kang, Yu-Ri Kim, Yea Eun Kang, Ju Hee Lee, Minho Shong, Hyon-Seung Yi
Frontiers in Endocrinology.2021;[Epub] CrossRef
Different Relationships Between Thyrotropin and Muscle Strength According to Sex and Age in Euthyroid Koreans (The 6th Korea National Health and Nutritional Examination Survey 2014–2015)
Seong Hee Ahn, Da Hea Seo, Yongin Cho, Mihye Jung, So Hun Kim, Seongbin Hong
Thyroid.2020; 30(12): 1710. CrossRef
A Significant Association of Upper Limb Muscle Strength with Thyroid Function in Overweight and Obese Population: A Study of the Sixth Korea National Health and Nutrition Examination Survey (KNHANES 2014-2015)
Jeongmin Lee, Kwanhoon Jo, Jeonghoon Ha, Dong-Jun Lim, Jung Min Lee, Sang-Ah Chang, Moo Il Kang, Min-Hee Kim, Flavia Magri
International Journal of Endocrinology.2020; 2020: 1. CrossRef
Muscle-derived IL-6 improved insulin resistance of C2C12 cells through activating AMPK and inhibiting p38MAPK signal pathway in vitro
Hui Tang, Shuai Deng, Jian-guang Cai, Xue-nan Ma, Man Liu, Liang Zhou
International Journal of Diabetes in Developing Countries.2019; 39(3): 486. CrossRef
Thyroid Function as a Predictor of Handgrip Strength Among Middle-Aged and Older Euthyroid Adults: The TCLSIH Cohort Study
Yeqing Gu, Ge Meng, Hongmei Wu, Qing Zhang, Li Liu, Xue Bao, Yawen Wang, Shunming Zhang, Shaomei Sun, Xing Wang, Ming Zhou, Qiyu Jia, Kun Song, Kaijun Niu
Journal of the American Medical Directors Association.2019; 20(10): 1236. CrossRef
Association of Serum TSH With Handgrip Strength in Community-Dwelling Euthyroid Elderly
Beom-Jun Kim, Seung Hun Lee, Carlos M Isales, Mark W Hamrick, Mi Kyung Kwak, Jung-Min Koh
The Journal of Clinical Endocrinology & Metabolism.2018; 103(11): 3986. CrossRef
Changes in Thyroid Hormone Levels Within the Normal and/or Subclinical Hyper- or Hypothyroid Range Do Not Affect Circulating Irisin Levels in Humans
Grigorios Panagiotou, Kalliopi Pazaitou-Panayiotou, Stavroula A. Paschou, Despina Komninou, Nikolaos Kalogeris, Andromachi Vryonidou, Christos S. Mantzoros
Thyroid.2016; 26(8): 1039. CrossRef
Thyroid-stimulating hormone improves insulin sensitivity in skeletal muscle cells via cAMP/PKA/CREB pathway-dependent upregulation of insulin receptor substrate-1 expression
Min Kyong Moon, Geun Hyung Kang, Hwan Hee Kim, Sun Kyoung Han, Young Do Koo, Sun Wook Cho, Ye An Kim, Byung-Chul Oh, Do Joon Park, Sung Soo Chung, Kyong Soo Park, Young Joo Park
Molecular and Cellular Endocrinology.2016; 436: 50. CrossRef
Brief Review of Articles in 'Endocrinology and Metabolism' in 2013
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Endocrinology and Metabolism.2014; 29(3): 251. CrossRef

Case Reports

Thyroid
Two Cases of Methimazole-Induced Insulin Autoimmune Syndrome in Graves' Disease: Eun Roh, Ye An Kim, Eu Jeong Ku, Jae Hyun Bae, Hye Mi Kim, Young Min Cho, Young Joo Park, Kyong Soo Park, Seong Yeon Kim, Soo Heon Kwak; Endocrinol Metab. 2013;28(1):55-60. Published online March 25, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.1.55

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Abstract PDF PubReader

We report here the cases of two females with Graves' disease who developed insulin autoimmune syndrome after treatment with methimazole. The patients exhibited a sudden altered mental state after treatment with methimazole for approximately 4 weeks. Patients had hypoglycemia with serum glucose below 70 mg/dL, and laboratory findings showed both high levels of serum insulin and high titers of insulin autoantibodies. The two women had never been exposed to insulin or oral antidiabetic agents, and there was no evidence of insulinoma in imaging studies. After glucose loading, serum glucose, and total insulin levels increased abnormally. One of the patient was found to have HLA-DRB1*0406, which is known to be strongly associated with methimazole-induced insulin autoimmune syndrome. After discontinuation of methimazole, hypoglycemic events disappeared within 1 month. Insulin autoantibody titer and insulin levels decreased within 5 months and there was no further development of hypoglycemic events. We present these cases with a review of the relevant literature.

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MingXu Lin, YuHua Chen, Jie Ning, Tatsuya Kin
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Yu-Shan Hsieh
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Case report: hypoglycemia secondary to methimazole-induced insulin autoimmune syndrome in young Taiwanese woman with Graves’ disease
Hsuan-Yu Wu, I-Hua Chen, Mei-Yueh Lee
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Linli Sun, Weijin Fang, Dan Yi, Wei Sun, Chunjiang Wang
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Gu Gao, Feng-fei Li, Yun Hu, Reng-na Yan, Bing-li Liu, Xiao-mei Liu, Xiao-fei Su, Jian-hua Ma, Gang Hu
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Yimin Shen, Xiaoxiao Song, Yuezhong Ren
BMC Endocrine Disorders.2019;[Epub] CrossRef
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David Church, Luís Cardoso, Richard G Kay, Claire L Williams, Bernard Freudenthal, Catriona Clarke, Julie Harris, Myuri Moorthy, Efthmia Karra, Fiona M Gribble, Frank Reimann, Keith Burling, Alistair J K Williams, Alia Munir, T Hugh Jones, Dagmar Führer,
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MANAGEMENT OF ENDOCRINE DISEASE: Pathogenesis and management of hypoglycemia
Nana Esi Kittah, Adrian Vella
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Insulin autoimmune syndrome during the administration of clopidogrel
Eijiro Yamada, Shuichi Okada, Tsugumichi Saito, Aya Osaki, Atushi Ozawa, Masanobu Yamada
Journal of Diabetes.2016; 8(4): 588. CrossRef
Hyperinsulinemic hypoglycemia associated with insulin antibodies caused by exogenous insulin analog
Chih-Ting Su, Yi-Chun Lin
Endocrinology, Diabetes & Metabolism Case Reports.2016;[Epub] CrossRef
Anti-tuberculosis Treatment-Induced Insulin Autoimmune Syndrome
Jung Suk Han, Han Ju Moon, Jin Seo Kim, Hong Il Kim, Cheol Hyeon Kim, Min Joo Kim
The Ewha Medical Journal.2016; 39(4): 122. CrossRef
2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis
Douglas S. Ross, Henry B. Burch, David S. Cooper, M. Carol Greenlee, Peter Laurberg, Ana Luiza Maia, Scott A. Rivkees, Mary Samuels, Julie Ann Sosa, Marius N. Stan, Martin A. Walter
Thyroid.2016; 26(10): 1343. CrossRef
Insulin Autoimmune Syndrome in a Patient with Hashimoto's Thyroiditis
In Wook Song, Eugene Han, Nan Hee Cho, Ho Chan Cho
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Thyroid
A Case of Acute Suppurative Thyroiditis with Thyrotoxicosis in an Elderly Patient: Bo Sang Kim, Kil Woo Nam, Jeong Eun Kim, Ji Hoon Park, Jun Sik Yoon, Jung Hwan Park, Sang Mo Hong, Chang Bum Lee, Yong Soo Park, Woong Hwan Choi, You Hern Ahn, Dong Sun Kim; Endocrinol Metab. 2013;28(1):50-54. Published online March 25, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.1.50

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Abstract PDF PubReader

Acute suppurative thyroiditis (AST) is a rare condition, as the thyroid gland is relatively resistant to infection. Thyroid function tests are usually normal in AST. A few cases of AST associated with thyrotoxicosis have been reported in adults. We report a case of AST that was associated with thyrotoxicosis in a 70-year-old woman. We diagnosed AST with thyroid ultrasonography and fine needle aspiration of pus. The patient improved after surgical intervention and had no anatomical abnormality. Fine needle aspiration is the best method for the difficult task of differentiating malignancy and subacute thyroiditis from AST with thyrotoxicosis. Earlier diagnosis and proper treatment for AST might improve the outcome.

Citations

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Acute suppurative thyroiditis with Graves disease – A very rare association
Inês Damásio, Joana Maciel, Maria Manuel Costa, Luisa Raimundo
Archives of Endocrinology and Metabolism.2023;[Epub] CrossRef
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Zeynab Seyedjavadeyn, Seyed Amir Miratashi Yazdi, Alireza Samimiat, Matin Vahedi
Journal of Medical Case Reports.2023;[Epub] CrossRef
Subakute Thyreoiditis und akute suppurative Thyreoiditis
Christian Trummer, Verena Theiler-Schwetz, Stefan Pilz
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Endocrinology and Metabolism.2014; 29(3): 251. CrossRef

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