- A Study on Insulin action using fibroblast of leprechaunism patients.
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Si Whan Koh, Yoo Joung Oh, Mi Koung Chang, Yun Soo Bae, Dong Kyu Jin
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Korean Diabetes J. 2006;30(1):39-46. Published online January 1, 2006
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DOI: https://doi.org/10.4093/jkda.2006.30.1.39
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 Abstract
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- BACKGROUND
Leprechaunism, which is caused by insulin receptor defect, is clinically characterized by hyperinsulinemia, stunted growth, dysmorphic somatic abnormalities, lipodystrophy and early death around 2-3 years of age. METHODS: In this study we describe 2 cases of Korean leprechaunism patients. In addition, the disturbed insulin induced effects such as glucose uptake, insulin binding assay, thymidine uptake and PDGF stimulated phosphorylation change were investigated using the fibroblasts from 1 Korean patient and those from 4 foreign leprechaunism patients. RESULTS: The morphologic study of fibroblasts derived from patient suggests that the fibroblasts of patient are less differentiated than the fibroblasts of control. Moreover, insulin induced pathways as well as PDGF stimulated phosphorylation change were disturbed in the fibroblasts of the patient. CONCLUSION: Our results suggest that the signal transduction in the fibroblasts of leprechaunism is reduced not only by insulin stimuli but also by other growth factors like PDGF.
- The Prevalence of Islet Cell Cytoplasmic Antibody in Korean Type 1 Diabetes: Possible Replacement with Combined Measurement of Anti-GAD, Anti-ICA512, and Anti-phogrin Antibodies.
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Kyoung Ah Kim, Dong Jun Kim, Jae Hoon Chung, Yong Ki Min, Moon Kyu Lee, Kwang Won Kim, Dong Kyu Jin, Kyung Soo Ko, Sang Jin Kim, Myung Shik Lee
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Korean Diabetes J. 2001;25(6):430-445. Published online December 1, 2001
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Abstract
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- BACKGROUND
Type 1 diabetes includes all forms of autoimmune-mediated and idiopathic beta-cell destruction leading to an absolute insulin deficiency. Evidence of an autoimmune pathogenesis was assessed by studying cytoplasmic islet cell antibodies (ICA), antibodies to glutamic acid decarboxylase (GADA), antibodies reacting with an islet tyrosine phosphatase-related molecule referred to as ICA512 (ICA512A), or its homologue phogrin (phogrin-A). In comparison with ICA, the best validation to assess the risk of type 1 diabetes, shows that a combination of antibodies to GADA with ICA512A has the power to detect a majority of ICA and 97~100% of subjects who progressed to overt diabetes. These findings suggest the possibility of replacing the laborious ICA test in the screening programs to identify subjects at risk of progressing to type 1 diabetes or forclassifying the stage of diabetes at the time of diagnosis. Up to now, it is unclear whether these results are applicable to the slowly progressive type 1 diabetes that appears to be more prevalent in Asian than in western countries. The prevalence of combined autoantibody testing (1 of GADA, ICA512A, or phogrin-A) was investigated in the patients with type 1 diabetes (typical and slowly progressive) and type 2 diabetes, and compared with that of ICA which is a more laborious and insensitive test. METHODS: The ICA assay was performed using immunoenzymatic staining of frozen human (blood group O) pancreatic sections with serial dilutions of serum samples with peroxidase-labeled protein A. For the GADA determination, commercially available GADA radioimmunoassay kits utilizing the 125I-labeled recombinant GAD65 (RSR , United Kingdom) as an antigen was used. Either ICA512A or phogrin-A were detected by a radioligand-binding assay after in vitro transcription and translation using the clone ICA512bdc or phogrin cDNA. Serum was obtainedfrom 76 patients with type 1 diabetes (mean age 22.8+/-14.0 years), 22 patients with slowly progressive type 1 diabetes (mean age 37.9+/-13.9 years) and 39 patients with type 2 diabetes (mean age 45.3+/-12.3 years). Typical and slowly progressive type 1 diabetes patients had the disease for between 4.0+/-4.6 and 10.1+/-9.5 years, respectively at the earliest serum sampling. RESULTS: 1) In typical type 1 diabetes, 30% of patients tested positive for ICA and 57% for the combined autoantibody test (1 of GADA, ICA512A, or phogrin-A). In the slowly progressive type 1 diabetes group, 18% of patients tested positive for ICA and 50% for the combined autoantibody test. In type 2 diabetes, 7.7% and 5.1% tested positive, respectively. 2) Ninety-six percent of ICA-positive patients expressed one or more of the 3 auto-antibody specificities in typical type 1 diabetes. Among the 53 ICA-negative patients with typical type 1 diabetes, 40% had one or more of these auto-antibodies. In the slowly progressive type 1 diabetes, 100% of the ICA-positive and 39% of the ICA- negative patients expressed one or more of the 3 autoantibody specificities. 3) Of the 23 patients with ICA-positive typical type 1 diabetes patients, 87% had a positive result for GADA, 48% for ICA512A, 44% for phogrin-A, and 96% for GADA or ICA512A. Of the 4 patients with ICA-positive slowly progressive type 1 diabetes, three had a positive result for GADA, and 1 for ICA512A. 4) When the prevalence of combined autoantibody testing was analyzed according to the duration of diabetes, the prevalence in patients tested within 4 years after the diagnosis and more than 4 years after the diagnosis was 61% and 52%, respectively in typical type 1 diabetes. Furthermore, that for the ICA was 37% and 21%, respectively. In the slowly progressive type 1 diabetes, the prevalence of combined auto-antibody testing was 88% and 25%, respectively (p<0.05), while that of ICA was 25% and 13%, respectively. 5) In typical type 1 diabetes, ICA were detected more frequently in patients younger than 15 years of age (48%) than in older patients (23%) (p<0.05), while the prevalence of combined auto-antibody testing -was not different according to the onset age (65% vs 53%). CONCLUSION: Combined autoantibody testing for GADA and ICA512A is more sensitive that ICA in type 1 diabetes. Therefore, it could replace the laborious ICA measurement and may be useful for discriminating the etiology of adult onset atypical diabetes.
- Measurement of Anti-Phogrin Antibody in Korean Autoimmune Deabetes; Comparison to Anti-IA-2 Antibody.
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Moon kyu Lee, Yong Ki Min, Myung Shik Lee, Sung Hoon Kim, Byoung Joon Kim, Dong Jun Kim, Jong Ryeal Hahm, Dong Kyu Jin, Kyoung Ah Kim, Kwang Won Kim
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Korean Diabetes J. 1999;23(3):269-277. Published online January 1, 2001
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Abstract
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- BACKGROUND
Since the discovery of IA-2 as a major autoantigen in type 1 diabetes, the question arose as to whether other PTPs (protein tyrosine phosphatases) could act as diabetic autoantigens as well. A novel PTP, designated IA-2 B (phogrin; phosphatase homologue in granules of insulinoma) was isolated that has a high sequence similarity to IA-2. Since some studies suggested that auto- immunity to phogrin, rather than IA-2 may be more closely associated with the development of type 1 diabetes, we measured the frequency of anti-phogrin antibody in Korean patients with type 1 diabetes and compared it with that of anti-IA-2 antibody/ anti-GAD antibody. METHODS: The anti-phogrin antibody and the anti-IA-2 antibody were measured by radioligand binding assays using in vitro transcribed and translated S-labeled phogrin and IA-2, respectively. Anti-GAD antibody was measured using a commercial radioimmunoassay kit (RSR, Cardiff, U.K.). The subjects in this study consisted of 41 patients with classical type 1 diabetes, 22 with slowly progressive type 1 diabetes, and 39 with type 2 diabetes. Their average mean age was 16.9 years, 37.9 years and 45.3 years respectively. RESULTS: The prevalence of anti-phogrin antibody, anti-IA-2 antibody and anti-GAD antibody in classical type 1 diabetes was 24.4%, 26.8% and 51.2% respectively. That, in slowly progressive type 1 diabetes was 0%, 9.1% and 40.9% respectively. When the anti-GAD antibody assay and the anti-IA-2 antibody assay were combined, the prevalence of autoantibodies was 58.5% in classical type 1 diabetes and 50% in slowly progressive type I diabetes. However, the addition of the anti-phogrin antibody to the anti-GAD antibody/anti-IA-2 antibody measurement did not significantly increase the prevalence of autoantibody. The level of the antiphogrin antibody was positively correlated with that of the anti-IA-2 antibody. The presence of the anti-phogrin antibody and the anti-IA-2 antibody was negatively correlated with the age at diagnosis. One patient with type 1 diabetes had the anti-phogrin antibody without the anti-IA-2 antibody. CONCLUSION: Combined measurement of the anti-phogrin antibody with the anti-IA-2 antibody/ anti-GAD antibody did not significantly increase the prevalence of autoantibodies in Korean patients with type 1 diabetes. In the majority of Korean type 1 diabetes patients, the anti-phogrin antibody appears to share epitopes with the anti-IA-2 antibody. However, a small proportion of type 1 diabetes patients may have a specific autoimmune response to phogrin.
- Combined Measurements of Anti-ICA512 and Anti-GAD Antibodies in Insulin-dependent Diabetes Mellitus and Slowly Progressive Insulin-dependent Diabetes Mellitus in Korea.
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Kyoung Ah Kim, Kyu Jung Ahn, Jae Hoon Chung, Yong Ki Min, Moon Kyu Lee, Phil Soo Oh, Dong Kyu Jin, Byung Tae Kim, Hae Joon Park, Kwang Won Kim, Myung Shik Lee
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Korean Diabetes J. 1998;22(4):482-490. Published online January 1, 2001
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Abstract
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- BACKGROUND
Type 1 diabetes mellitus is a chronic autoimmune disease in which circulating antibodies to various islet-specific antigens including autoantibodies to glutamic acid decarboxylase (GADAb), antibodies reacting with an islet tyrosine phosphatase-related molecule termed as ICA512 (ICA512Ab), and insulin autoantibodies are frequently detected. These autoantibodies could be useful for presymptomatic diagnosis of type 1 diabetes mellitus, and tbeir presence suggest some patients with atypical diabetes mellitus that appears to be more prevalent in Asian than in western countries have autoimmune characteristics. ICA512Ab was discovered in 1992 and, when combined with GADAb, may increase the diagnostic sensitivity in autoimmune diabetes. In an attempt to study the autoimmune feature of atypical diabetes mellitus, we studied the prevalence of ICA512Ab using an in vitro transcription and translation method in the patients with insulin-dependent diabetes mellitus (IDDM), slowly progressive insulin-dependent diabetes mellitus (SPIDDM) and non-msulin-dependent diabetes mellitus (NIDDM), and compared it with that of GADAb. METHODS: ICA512Ab were measured by a radioimmunoprecipitation method using in vitro transcribed and translated S-methionine-labeled ICA512. GADAb were measured using a commercial radioimmunoassay kit (RSR, United Kingdom). The subjects in this study consisted of 43 patients with IDDM, 32 with SPIDDM, and 40 witb NIDDM. Their mean age was 21.2+14.5 years, 50.1+17.1 years, 52.5+13.4 years, respectively. RESULTS: The prevalence of ICA512Ab and GADAb in IDDM was 29 % and 51 %, respectively. That in SPIDDM was 9 % and 29 %; in NIDDM, 0 % and 2.5 %, respectively. When two antibodies were combined, 60 % of IDDM and 50 % of SPIDDM had the autoantibodies. When we analyzed the prevalence of autoantibodies according to the duration of diabetes, the prevalence of ICA 512Ab in patients tested within 4 years after the rliagnosis and more than 4 years after the diagnosis was 35 % and 19 %, respectively in IDDM. And also that of GADAb was 59 % and 38 %, respectively. In SPlDDM, the prevalence of ICA512Ab was 13 % and 7 %, respectively, while that of GADAb was 67 % and 14 % (p<0.05), respectively. In IDDM, ICA512Ab were more frequently detected in patients younger than 15 years ot age (45 %) than in older ones (14%) (p<0.05) while the prevalence of GADAb was not different according to the age (55 % vs 44 %). CONCLUSION: ICA512Ab are detected in some patients with autoimmune diabetes, while their prevalence is lower than that of GADAb. However, ICA512Ab, in combination with GADAb, increases the sensitivity ot autoantibody tests in autoimmune diabetes. Some of SPIDDM have an autoimmune etiology.
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