Endocrinology and Metabolism

Original Article

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

Response

Obesity and Metabolism
Response: 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.): Eun Ju Lee, Mi-Kyung Kim; Endocrinol Metab. 2013;28(4):348-349. Published online December 12, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.4.348

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Original Article

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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Abstract PDF PubReader

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%.

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Environment International.2022; 165: 107298. CrossRef
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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
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How Continuity in Service Impacts Process Variability: Evidence from a Primary Care Setting
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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
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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
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Hye-jin Yoon, Yong-ho Lee, Kwang Joon Kim, So Ra Kim, Eun Seok Kang, Bong-Soo Cha, Hyun Chul Lee, Byung-Wan Lee
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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.)
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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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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

Original Articles

Lanreotide Therapy in Graves' Ophthalmopathy.: Il Seong Nam-Goong, Eun Ju Lee, Jung Hwoon Kim, Jong Chul Won, Woo jae Lee, Jung Hee Han, sung Jin Lee, Sang Wook Kim, Moo Kon Son, Ho Hye Lee, Il Min Ahn; J Korean Endocr Soc. 2001;16(1):18-25. Published online February 1, 2001

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Abstract PDF: BACKGROUND
Graves' ophthalmopathy (GO) is an autoimmune process that affects the orbital tissues. Patients with GO are usually treated with high doses of corticosteroids, retrobulbar irradiation, or by surgical decompression, however, those have some adverse effect. Recently, a synthetic somatostatin analogue has been reported for the treatment of GO. This study was performed prospectively to evaluate the therapeutic effects of lanreotide, a potent long acting synthetic somatostatin analogue, in patients that have GO. METHODS: Eight patients with moderate to severe GO (M:F=1:7, age 39.0+/-11.8 years) were included. Patients who had been treated with other modalities than GO, or had a systemic illness such as diabetes were excluded. Eight patients were given lanreotide, 40mg IM every 2 weeks over a period of 8 weeks. Their therapeutic responses were evaluated using an orbital CT or MRI and by ophthalmologic examinations. RESULTS: After 8 weeks' of lanreotide treatment, 4 patients showed decreased scores in the NOSPECS classification (p=0.059) as well as 5 patients in their clinical activity scores(p=0.109). All of the 8 patients showed improvements according to clinical evaluation criteria (p=0.008). Significant changes in the thickness of both the lateral rectus and superior rectus muscles were observed (p<0.05). No patient showed serious adverse effects related to lanreotide therapy during the follow-up periods. CONCLUSION: We conclude that lanreotide therapy has clinical benefits and show radiologic improvements in GO. Considering the minimal side-effects of lanreotide compared to those of corticosteroid, lanreotide therapy should be considered for use in selected patients that have Graves' ophthalmopathy

The Role of Preoperative and Postoperative Thyroglobulin Measurements in The Detection of Well Differentiated Thyroid Carcinomas Recurrence.: Seong Jin Lee, Jong Chul Won, Ha Young Kim, Jung Hee Han, Eun Ju Lee, Sang Wook Kim, Jin Sook Ryu, Dae Hyuk Moon, Suk Joon Hong, Il Min Ahn; J Korean Endocr Soc. 2000;15(4-5):542-553. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Thyroglobulin (Tg) measurement is primarily used to monitor patients with well differentiated thyroid carcinomas (WDTC) for tumor recurrence. We evaluated the correlations between fold responses of thyroglobulin levels and TNM stages (and MACIS scores) at recurrent group. Also correlations between preoperative Tg levels and Tg (on or off replacement) levels at the time of recurrence were evaluated. Postoperative Tg levels between recurrent and non-recurrent groups were analyzed for the use of assessing risk of recurrence. METHODS: One hundred twenty five cases of WDTC who had total thyroidectomy and (131)I remnant thyroid ablation were finally included in this study. After optimal TSH stimulations (>30 microIU/mL), (131)I whole body scan (WBS) was performed. We interpreted as a recurrence only when abnormal findings on the (131)I WBS were detected. Preoperative, immediate postoperative and follow-up Tg tlevels were regularly measured. RESULTS: Difference of preoperative Tg levels between recurrent and non-recurrent groups was not significant (27.5+/-4.2 ng/mL vs. 16.0+/-10.9 ng/mL). Also differences of immediate postoperative Tg (on or off replacement) levels between two groups was not significant (2.4+/-3.8 ng/mL vs. 3.6+/-3.l ng/mL, 33.4+/-4.8 ng/ml vs. 24.5+/-4.8 ng/mL, respectively). Tg levels on replacement at 24 months after surgery between recurrent and non-recurrent groups were significantly different (2.2+/-4.8 ng/mL, 15.9+/-6.5 ng/mL, p<0.001) and also Tg levels off replacement between recurrent and non-recurrent groups were significantly different (4.0+/-6.6ng/mL vs. 49.4+/-9.3 ng/mL, p<0.001). Fold responses between recurrent and non-recurrent groups were significantly different (2.0+/-3.1 ng/mL, 5.0+/-4.1 ng/mL, p=0.009). Fold responses between recurrent and non- recurrent groups were significantly different according to TNM stages (p=0.002) but not different according to MACIS scores. Preoperative Tg levels were correlated Tg (on or off replacement) levels at the time of recurrence (p=0.02, r=0.4: p<0.001, r=0.6, respectively). Sensitivity, specificity, accuracy of Tg levels over 2 ng/mL on replacement were 95%, 73%, 84% but those of Tg levels over 7 ng/mL off replacement were 83%, 70%, 77%. CONCLUSION: Fold responses may predict prognosis of WDTC. Small postoperative increase in serum Tg levels may indicate a large increase of tumor mass in cases of normal or low preoperative Tg levels. Tg levels over 2 ng/mL on replacement or 7 ng/mL off replacement during follow-up may suggest the recurrence of WDTC.

Clinical Significance of Human Sodium Iodide Symporter mRNA Expressions in Primary and Metastatic Papillary Thyroid Carcinoma.: Seong Jin Lee, Hyun Joo Park, Eun Ju Lee, Ha Young Kim, Jin Kyu Koh, Ki Young Park, Sung Bae Kim, Gyung Yup Gong, Suk Joon Hong, Il Min Ahn, Sang Hee Kim; J Korean Endocr Soc. 1999;14(3):514-519. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The iodide transport into thyroid cells is an essential step in the biosynthesis of thyroid hormones. The sodium iodide symporter (NIS) which is responsible for iodide transport was cloned recently and identified as a plasma membrane glycoprotein. Recent report suggested the absence of human NIS (hNIS) mRNA expression of papillary carcinoma in thyroid indicates absence of response on radioiodine therapy for distant metastasis. To understand the change of hNIS expression at the stage of metastasis in papillary thyroid carcinomas, we evaluated the expression levels of hNIS mRNA in primary and lymph node metastatic papillary carcinoma tissues. METHODS: Seven pairs of primary and lymph node metastatic tissues were included in this study. The level of hNIS mRNA in lymph node metastatic tissues and primary tissues were evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR). The level of GAPDH mRNA was used as internal control. RESULTS: Two among 6 lymph node metastatic tissues did not show hNIS mRNA even with significant hNIS expressions in papillary carcinoma tissues in thyroid. The levels of hNIS expression of remaining 4 lymph node metastatic tissues were lower than those of corresponding primary tissues. Interestingly, one case showed no hNIS expression in primary tissue, but significant hNIS expression in lymph node metastatic tissue. There was no correlation in hNIS mRNA expression between primary and lymph node metastatic tissues. CONCLUSION: No correlation was found in hNIS mRNA expression between primary and lymph node metastatic tissues, suggesting the measurements of hNIS mRNA level in primary tissues may not predict therapeutic response to radioactive iodine.

Case Report

A Case of Graves' Disease with Spuriously Elevsted TSH due to Interference of Heterophilin Actibodies.: Jeong Hee Han, Sung Jin Lee, Young Rok Sin, Eun Ju Lee, Eun Sook Kim, Sang Wook Kim, Jin Yub Kim, Il Min Ahn; J Korean Endocr Soc. 1999;14(1):160-164. Published online January 1, 2001

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Abstract PDF: Thyroid-stimulating hormone (TSH) is the most sensitive marker reflecting thyroid function. TraditionaUy, TSH concentration was measured by the method of RadioImmunoAssay (RIA) with the detection limits around 1 to 2 mIU/L, which was unable to differentiate hyperthyroid status. Since 1980s, owing to the sensitive assay for TSH, immunoradiometric assay (IRMA), it has been possible to detect low concentration of TSH by 0.001 mlU/L. TSH is composed of two glycopeptide subunits, a-subunit and B-subunit. Monoclonal antibodies, directed against two different sites of the TSH peptides, are used in IRMA. One antibody is directed toward the specific B-subunit of TSH molecule and is used to extract it from serum, a second antibody labelled with a radioactive material is then attached to the separated TSH to form "sandwhich" molecule that can be measured. Generally, mouse monoclonal antibodies are used as capture and detection antibodies. Infrequently, when there is heterophilic antibody, i.e. human anti-mouse antibody (HAMA), TSH can be measured as spuriously elevated, since HAMA may form a link between the signal and capture molecules. We report a case of inappropriately elevated TSH concentration due to heterophilic antibody, later diagnosed as Graves disease. A 41-year-old woman visited our clinic with the chief complaints of hand tremor, hyperphagia, weight loss for 3 months. Two years earlier, she underwent total colectomy due to colon cancer and had treat on multiple chemotherapies. The results of thyroid function test shows that TSH was 0.77 mIU/L, free T was 7.1 ng/dL (0.8~1.9), free T was 11.3 pg/mL (0.2~5.5). Thyroid specific auto- antibody results were anti-Tg-Ab 21.3 m/mL(0 100), anti-TPO-Ab 87.9m/mL(0100), TBIAb 7.8% (-15/15). Thyroid scan showed that radioactiveiodine uptake was increased and thyroid gland wasenlarged diffusely. Because TSH level was elevated, further evaluations were performed to differentiate with TSH producing pituitary tumor and pituitary resistance to thyroid hormone. Sellar MRI was normal, TRH stimulation test showed flat response. Since spurious elevation of TSH is possible at the presence of hetrophilic antibody, we rechecked TSH concentration after adding mouse monoclonal antibody to the patients serum with result of TSH less than 0.05 mIU/L. She was able to be diagnosed as Graves disease, and started with methimazole. Three months later, thyroid function test showed that TSH was 10.5 mIU/L, free T4 was 1.0 ng/dL, free T3 was 4.0 pg/mL. TSH level after removal the effect of heterophilic antibody with mouse monoclonal antibody was 0.71 mIU/L. Neutropenia was developed 5 months after methimazole therapy, to stop antithyroid medication. With the plan of radioactive iodine therapy if she relapses, she is being followed with periodic thyroid function test. We report a case of Graves disease with spuriously elevated TSH due to the effect of heterophilic antibodies.

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