Endocrinology and Metabolism

Original Articles

Co-Culture of α TC-6 Cells and β TC-1 Cells: Morphology and Function: Sung Man Kim, Eun Ju Lee, Hye Sook Jung, Na Han, You Jeong Kim, Tae Kyoon Kim, Tae Nyun Kim, Min Jeong Kwon, Soon Hee Lee, Jeong Hyun Park, Byoung Doo Rhee, Mi-Kyung Kim; Endocrinol Metab. 2015;30(1):92-97. Published online March 27, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.1.92

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Background

In vitro experiments using only β-cell lines instead of islets are limited because pancreatic islets are composed of four different types of endocrine cells. Several recent studies have focused on cellular interactions among these cell types, especially α- and β-cells. Because islet isolation needs time and experience, we tested a simple co-culture system with α- and β-cells. Their morphology and function were assessed by comparison to each single cell culture and pancreatic islets.

Methods

α TC-6 cells and β TC-1 cells were maintained in Dulbecco's Minimal Essential Medium containing 5 mM glucose and 10% fetal bovine serum. Cells were mixed at a 1:1 ratio (5×10⁵) in 6-well plates and cultured for 24, 48, and 72 hours. After culture, cells were used for insulin and glucagon immunoassays and tested for glucose-stimulated insulin secretion (GSIS).

Results

α TC-6 and β TC-1 cells became condensed by 24 hours and were more strongly compacted after 48 hours. β TC-1 cells showed both β-β and β-α cell contacts. GSIS increased with increasing glucose concentration in co-cultured cells, which showed lower secreted insulin levels than β TC-1 cells alone. The increase in the secreted insulin/insulin content ratio was significantly lower for co-cultured cells than for β-cells alone (P=0.04). Compared to islets, the α-/β-cell co-culture showed a higher ratio of GSIS to insulin content, but the difference was not statistically significant (P=0.09).

Conclusion

α TC-6 and β TC-1 cells in the co-culture system showed cell-to-cell contacts and a similar stimulated insulin secretion pattern to islets. The co-culture system may be used to better mimic pancreatic islets in in vitro assessments.

Citations

Citations to this article as recorded by

Recent advances in the design of implantable insulin secreting heterocellular islet organoids
M. Birgul Akolpoglu, Yasemin Inceoglu, Ugur Bozuyuk, Ana Rita Sousa, Mariana B. Oliveira, João F. Mano, Seda Kizilel
Biomaterials.2021; 269: 120627. CrossRef
Pancreatic β Cells Inhibit Glucagon Secretion from α Cells: An In Vitro Demonstration of α–β Cell Interaction
Wenqian Gu, Camilla Christine Bundgaard Anker, Christine Bodelund Christiansen, Tilo Moede, Per-Olof Berggren, Kjeld Hermansen, Søren Gregersen, Per Bendix Jeppesen
Nutrients.2021; 13(7): 2281. CrossRef
The Role of Pancreatic Alpha Cells and Endothelial Cells in the Reduction of Oxidative Stress in Pseudoislets
Fredrik C. Wieland, Mireille M.J.P.E. Sthijns, Thomas Geuens, Clemens A. van Blitterswijk, Vanessa L.S. LaPointe
Frontiers in Bioengineering and Biotechnology.2021;[Epub] CrossRef

Bone Metabolism
Efficacy of a Once-Monthly Pill Containing Ibandronate and Cholecalciferol on the Levels of 25-Hydroxyvitamin D and Bone Markers in Postmenopausal Women with Osteoporosis: In-Jin Cho, Ho-Yeon Chung, Sung-Woon Kim, Jae-Won Lee, Tae-Won Lee, Hye-Soon Kim, Sin-Gon Kim, Han Seok Choi, Sung-Hee Choi, Chan Soo Shin, Ki-Won Oh, Yong-Ki Min, Jung-Min Koh, Yumie Rhee, Dong-Won Byun, Yoon-Sok Chung, Jeong Hyun Park, Dong Jin Chung, Minho Shong, Eun-Gyoung Hong, Chang Beom Lee, Ki Hyun Baek, Moo-Il Kang; Endocrinol Metab. 2015;30(3):272-279. Published online December 9, 2014; DOI: https://doi.org/10.3803/EnM.2015.30.3.272

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Background

The present study evaluated the efficacy of a combination of ibandronate and cholecalciferol on the restoration of the levels of 25-hydroxyvitamin D (25[OH]D) and various bone markers in postmenopausal women with osteoporosis.

Methods

This was a randomized, double-blind, active-controlled, prospective 16-week clinical trial conducted in 20 different hospitals. A total of 201 postmenopausal women with osteoporosis were assigned randomly to one of two groups: the IBN group, which received a once-monthly pill containing 150 mg ibandronate (n=99), or the IBN+ group, which received a once-monthly pill containing 150 mg ibandronate and 24,000 IU cholecalciferol (n=102). Serum levels of 25(OH)D, parathyroid hormone (PTH), and various bone markers were assessed at baseline and at the end of a 16-week treatment period.

Results

After 16 weeks of treatment, the mean serum levels of 25(OH)D significantly increased from 21.0 to 25.3 ng/mL in the IBN+ group but significantly decreased from 20.6 to 17.4 ng/mL in the IBN group. Additionally, both groups exhibited significant increases in mean serum levels of PTH but significant decreases in serum levels of bone-specific alkaline phosphatase and C-telopeptide of type 1 collagen (CTX) at 16 weeks; no significant differences were observed between the groups. However, in subjects with a vitamin D deficiency, IBN+ treatment resulted in a significant decrease in serum CTX levels compared with IBN treatment.

Conclusion

The present findings demonstrate that a once-monthly pill containing ibandronate and cholecalciferol may be useful for the amelioration of vitamin D deficiency in patients with postmenopausal osteoporosis. Moreover, this treatment combination effectively decreased serum levels of resorption markers, especially in subjects with a vitamin D deficiency, over the 16-week treatment period.

Citations

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Effect of vitamin D supplementation or fortification on bone turnover markers in women: a systematic review and meta-analysis
Nasrin Nasimi, Sanaz Jamshidi, Aida Askari, Nazanin Zolfaghari, Erfan Sadeghi, Mehran Nouri, Nick Bellissimo, Shiva Faghih
British Journal of Nutrition.2024; 131(9): 1473. CrossRef
Quality of life and patient satisfaction with raloxifene/cholecalciferol combination therapy in postmenopausal women
Dong-Yun Lee, Yoon-Sok Chung
Scientific Reports.2022;[Epub] CrossRef
Efficacy of risedronate with cholecalciferol on bone mineral density in Korean patients with osteoporosis
So Young Park, Moo-Il Kang, Hyung Moo Park, Yumie Rhee, Seong Hwan Moon, Hyun Koo Yoon, Jung-Min Koh, Jae Suk Chang, In Joo Kim, Ye Yeon Won, Ye Soo Park, Hoon Choi, Chan Soo Shin, Taek Rim Yoon, Sung-Cheol Yun, Ho-Yeon Chung
Archives of Osteoporosis.2020;[Epub] CrossRef
Efficacy and safety of vitamin D3 B.O.N intramuscular injection in Korean adults with vitamin D deficiency
Han Seok Choi, Yoon-Sok Chung, Yong Jun Choi, Da Hea Seo, Sung-Kil Lim
Osteoporosis and Sarcopenia.2016; 2(4): 228. CrossRef
Pharmacologic treatment of osteoporosis
Yong-Ki Min
Journal of the Korean Medical Association.2016; 59(11): 847. CrossRef

Obesity and Metabolism
A1c Variability Can Predict Coronary Artery Disease in Patients with Type 2 Diabetes with Mean A1c Levels Greater than 7: Eun Ju Lee, You Jeong Kim, Tae Nyun Kim, Tae Ik Kim, Won Kee Lee, Mi-Kyung Kim, Jeong Hyun Park, Byoung Doo Rhee; Endocrinol Metab. 2013;28(2):125-132. Published online June 18, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.2.125

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Background

Recent studies suggested that the association of acute glucose variability and diabetic complications was not consistent, and that A1c variability representing long term glucose fluctuation may be related to coronary atherosclerosis in patients with type 1 diabetes. In this study, we attempt to determine whether or not A1c variability can predict coronary artery disease (CAD) in patients with type 2 diabetes.

Methods

We reviewed data of patients with type 2 diabetes who had undergone coronary angiography (CAG) and had been followed up with for 5 years. The intrapersonal standard deviation (SD) of serially-measured A1c levels adjusted by the different number of assessments among patients (adj-A1c-SD) was considered to be a measure of the variability of A1c.

Results

Among the 269 patients, 121 of them had type 2 diabetes with CAD. In patients with A1c ≥7%, the mean A1c levels and A1c levels at the time of CAG among the three groups were significantly different. The ratio of patients with CAD was the highest in the high adj-A1c-SD group and the lowest in the low adj-A1c-SD group (P=0.017). In multiple regression analysis, adj-A1c-SD was an independent predictor for CAD in subjects with A1c ≥7% (odds ratio, 2.140; P=0.036).

Conclusion

Patients with higher A1c variability for several years showed higher mean A1c levels. A1c variability can be an independent predictor for CAD as seen in angiographs of patients with type 2 diabetes with mean A1c levels over 7%.

Citations

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Intermediate- and long-term associations between air pollution and ambient temperature and glycated hemoglobin levels in women of child bearing age
Mike Z. He, Itai Kloog, Allan C. Just, Iván Gutiérrez-Avila, Elena Colicino, Martha M. Téllez-Rojo, María Luisa Pizano-Zárate, Marcela Tamayo-Ortiz, Alejandra Cantoral, Diana C. Soria-Contreras, Andrea A. Baccarelli, Robert O. Wright, Maayan Yitshak-Sade
Environment International.2022; 165: 107298. CrossRef
Correlation between HbA1c and Triglyceride Level with Coronary Stenosis Degree in Type 2 Diabetes Mellitus with Coronary Heart Disease
Laily Adninta, Indranila Samsuria, Edward Kurnia Setiawan Limijadi
Open Access Macedonian Journal of Medical Sciences.2022; 10(B): 944. CrossRef
Long-Term Glycemic Variability and Vascular Complications in Type 2 Diabetes: Post Hoc Analysis of the FIELD Study
Emma S Scott, Andrzej S Januszewski, Rachel O’Connell, Gregory Fulcher, Russell Scott, Antero Kesaniemi, Linda Wu, Stephen Colagiuri, Anthony Keech, Alicia J Jenkins
The Journal of Clinical Endocrinology & Metabolism.2020; 105(10): e3638. CrossRef
How Continuity in Service Impacts Process Variability: Evidence from a Primary Care Setting
Vishal Ahuja, Carlos Alvarez, Bradley R. Staats
SSRN Electronic Journal .2019;[Epub] CrossRef
Association of hemoglobin A1c variability and the incidence of heart failure with preserved ejection fraction in patients with type 2 diabetes mellitus and arterial hypertension
Jun Gu, Yu-Qi Fan, Jun-Feng Zhang, Chang-Qian Wang
Hellenic Journal of Cardiology.2018; 59(2): 91. CrossRef
Prognostic impact of HbA1c variability on long-term outcomes in patients with heart failure and type 2 diabetes mellitus
Jun Gu, Jian-an Pan, Yu-qi Fan, Hui-li Zhang, Jun-feng Zhang, Chang-qian Wang
Cardiovascular Diabetology.2018;[Epub] CrossRef
Cardiovascular Autonomic Neuropathy Predicts Higher HbA1c Variability in Subjects with Type 2 Diabetes Mellitus
Yeoree Yang, Eun-Young Lee, Jae-Hyoung Cho, Yong-Moon Park, Seung-Hyun Ko, Kun-Ho Yoon, Moo-Il Kang, Bong-Yun Cha, Seung-Hwan Lee
Diabetes & Metabolism Journal.2018; 42(6): 496. CrossRef
Glycated hemoglobin level is an independent predictor of major adverse cardiac events after nonfatal acute myocardial infarction in nondiabetic patients
Chin-Lan Chen, David H.-T. Yen, Chin-Sheng Lin, Shih-Hung Tsai, Sy-Jou Chen, Wayne H.-H. Sheu, Chin-Wang Hsu
Medicine.2017; 96(18): e6743. CrossRef
Randomized, Open-Label, Parallel Group Study to Evaluate the Effect of Internet-Based Glucose Management System on Subjects with Diabetes in China
Hun-Sung Kim, Chenglin Sun, So Jung Yang, Lin Sun, Fei Li, In Young Choi, Jae-Hyoung Cho, Guixia Wang, Kun-Ho Yoon
Telemedicine and e-Health.2016; 22(8): 666. CrossRef
Association between hemoglobin A1c variability and subclinical coronary atherosclerosis in subjects with type 2 diabetes
Hae Kyung Yang, Borami Kang, Seung-Hwan Lee, Kun-Ho Yoon, Byung-Hee Hwang, Kiyuk Chang, Kyungdo Han, Gunseog Kang, Jae Hyoung Cho
Journal of Diabetes and its Complications.2015; 29(6): 776. CrossRef
Glycated Albumin Levels in Patients with Type 2 Diabetes Increase Relative to HbA1cwith Time
Hye-jin Yoon, Yong-ho Lee, Kwang Joon Kim, So Ra Kim, Eun Seok Kang, Bong-Soo Cha, Hyun Chul Lee, Byung-Wan Lee
BioMed Research International.2015; 2015: 1. CrossRef
Brief Review of Articles in 'Endocrinology and Metabolism' in 2013
Won-Young Lee
Endocrinology and Metabolism.2014; 29(3): 251. CrossRef
Inverse Association between Glycated Albumin and Insulin Secretory Function May Explain Higher Levels of Glycated Albumin in Subjects with Longer Duration of Diabetes
Yong-ho Lee, Mi Hyang Kown, Kwang Joon Kim, Eun Young Lee, Daham Kim, Byung-Wan Lee, Eun Seok Kang, Bong Soo Cha, Hyun Chul Lee, Marià Alemany
PLoS ONE.2014; 9(9): e108772. CrossRef
HbA1c Variability and Micro- and Macrovascular Complications of Diabetes
Hae Kyung Yang, Seung-Hwan Lee
The Journal of Korean Diabetes.2014; 15(4): 202. CrossRef
Letter: A1c Variability Can Predict Coronary Artery Disease in Patients with Type 2 Diabetes with Mean A1c Level Greater than 7 (Endocrinol Metab 2013;28:125-32, Eun Ju Lee et al.)
Hye Seung Jung
Endocrinology and Metabolism.2013; 28(4): 346. CrossRef

Case Report

Thyrotoxic Periodic Paralysis Induced by Dexamethasone.: Eun Ju Lee, Tae Kyoon Kim, Min Jeong Kwon, Soon Hee Lee, Jeong Hyun Park; Endocrinol Metab. 2012;27(4):299-302. Published online December 20, 2012; DOI: https://doi.org/10.3803/EnM.2012.27.4.299

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Abstract PDF

Thyrotoxic periodic paralysis (TPP) is a disease characterized by sudden onset and muscle paralysis. It occurs in the setting of hypokalemia of thyrotoxicosis. Cases of TPP induced by a glucocorticoid such as prednisolone or methylprednisolone have been reported. We report on two patients, each of whom received a dexamethasone injection and subsequently developed TPP. Both patients experienced sudden, flaccid paralysis of both extremities after the injection but recovered completely after receiving a potassium replacement. Laboratory results revealed thyrotoxicosis. The patients were diagnosed with Graves' disease and discharged after receiving treatment with methimazole and propranolol. This report provides the clinical description of TPP induced by dexamethasone injection. These cases suggest that clinicians must consider the presence of hyperthyroid disease in patients who develop acute paralysis after treatment with a glucocorticoid, even in the absence thyrotoxic symptoms. Furthermore, physicians should be aware that TPP can occur even in response to dexamethasone used for treatment of thyrotoxic crisis or Graves' ophthalmopathy.

Citations

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Glucocorticoid-Induced Hypokalemic Periodic Paralysis after Short-Term Use of Tenofovir with Hypophosphatemia: A Case Report
Yujin Shin, Yonglee Kim, Kyong Young Kim, Jong Ha Baek, Soo Kyoung Kim, Jung Hwa Jung, Jong Ryeal Hahm, Min Young Kim, Jaehoon Jung, Hosu Kim
Medicina.2021; 58(1): 52. CrossRef

Clinical Trial

Effect of Omega-3 Fatty Acids on Low Density Lipoprotein Subfraction, Adiponectin and Apolipoprotein B in Type 2 Diabetic Patients.: Haejung Jun, Junghae Ko, Hyesook Jung, Changshin Yoon, Taekyoon Kim, Minjeong Kwon, Soonhee Lee, Jihye Suk, Mikyung Kim, Dukkyu Kim, Jeong Hyun Park; Endocrinol Metab. 2011;26(3):218-224. Published online September 1, 2011; DOI: https://doi.org/10.3803/EnM.2011.26.3.218

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Abstract PDF

BACKGROUND
Omega-3 fatty acids derived from fish oil have been reported to exert a beneficial effect on reducing cardiovascular disease. Reports about their mechanism have generated several interesting findings, including a change in small dense low density lipoprotein (sdLDL) cholesterol proportion, adiponectin, and apolipoprotein B (apoB), in addition to changes in the lipid profile. The principal objective of our study was to evaluate the effects of omega-3 fatty acids on plasma sdLDL, adiponectin, apoB100, and B48 in type 2 diabetic patients with hypertriglyceridemia. METHODS: We randomized 28 type 2 diabetic patients in a placebo-controlled, double-blind trial to receive either omega-3 fatty acids or placebo, both administered at a dose of 4 g daily for 12 weeks. LDL subfractions prior to and after treatment were separated via low-speed ultracentrifugation and analyzed via immunoelectrophoresis. Adiponectin, apoB100, and B48 levels were measured using an ELISA kit. RESULTS: sdLDL proportions were reduced in the omega-3 fatty acids group by 11% after 12 weeks of treatment (n = 17, P = 0.001), and were reduced by 4% in the control group (n = 11, P = 0.096). The patients receiving the omega-3 fatty acids evidenced a significant reduction in the levels of triglyceride (P = 0.001), apoB100, and B48 after 12 weeks (P = 0.038 and P = 0.009, respectively) relative to the baseline. Omega-3 fatty acids supplementation increased fasting blood glucose (P = 0.011), but the levels of HbA1c in each group did not change to a statistically significance degree. The adiponectin value was not reduced in the omega-3 fatty acids group (P = 0.133); by way of contrast, the placebo group evidenced a significant reduction in adiponectin value after 12 weeks (P = 0.002). CONCLUSION: Omega-3 fatty acid treatment proved effective in the reduction of atherogenic sdLDL and apoB in type 2 diabetic patients (Clinical trials reg. no. NCT 00758927, clinicaltrials.gov).

Citations

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Blood Flow Improvement Effect of Bokbunja (Rubus coreanus) Seed Oil in High-Fat Diet-Fed Mouse Model
Hyelin Jeon, Sungmin Kwak, Su-Jin Oh, Hyun Soo Nam, Doo Won Han, Yoon Seok Song, Jinwoo Song, Kyung-Chul Choi
Journal of the Korean Society of Food Science and Nutrition.2015; 44(8): 1105. CrossRef
Fatty Acid Compositions, Mineral and Vitamin Contents of the Antarctic Krill (Euphausia superba)
Han-Soo Kim, Min-A Kim, Duan Yishan, Seong-Ho Jang, Dong-Soo Kang, Won-Ki Lee, Chun-Sik Lee, Jae-Young Ryu
Journal of Environmental Science International.2014; 23(1): 47. CrossRef

Original Article

The Effect of Atorvastatin and Simvastatin on NIS Expression of the TPC-1 Cell under the Therapeutic Blood Concentrations.: Tae Kyoon Kim, Hye Sook Jung, Chang Shin Yoon, Jung Hae Ko, Hae Jung Jun, Min Jung Kwon, Sun Hee Lee, Mi Kyung Kim, Jeong Hyun Park; Endocrinol Metab. 2010;25(3):192-198. Published online September 1, 2010; DOI: https://doi.org/10.3803/EnM.2010.25.3.192

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Abstract PDF: BACKGROUND
Although so many experimental trials have been done to improve the redifferentiation and responsiveness of radioiodide therapy, they have not yet yielded any satisfactory results. As statins inhibit both farnesylation and geranylgeranylation, they have been reported to have an antineoplastic and redifferentiation effect in experimental and clinical studies. In this study, we investigated the relationship between statins and the alteration of the NIS expression and, TPC-1 cell apotosis to evaluate the possibility of using statins as adjuvant therapeutic agents for papillary thyroid cancer. METHODS: We used the TPC-1 cell lines for our experiments. Cell viabilities were measured by CCK-8. The degrees of apoptosis and, the expressions of NIS mRNA and NIS protein were measured by flow cytometry, semi quantitative RT-PCR and Western blot assay. RESULTS: Increased levels of NIS mRNA and NIS protein were observed under therapeutic blood concentrations (concentrations of simvastatin: 20, 50, 80 nM, concentrations of atorvastatin: 50, 80,110 nM), but the dose-response relationship was only manifested within simvastatin. The TPC-1 cells showed a concentration dependent decrease of viability and an increase of apoptosis not under therapeutic blood concentrations, but under excessively high concentrations (after treatment with 10-50 microM of atorvastatin and with 1-10 microM of simvastatin). CONCLUSION: The results of this study show that effective therapeutic blood concentrations of simvastatin and atorvastatin can give a favorable effect on the NIS expression under effective therapeutic blood concentrations. Therefore, we demonstrated the possibility that simvastatin and atorvastatin might have an important role as adjuvant therapeutic agents to improve the responsiveness of radioiodide therapy for papillary thyroid cancer. Further studies are needed to clarify this issue.

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