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10 "Insulin secretion"
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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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  • 38 Download
AbstractAbstract PDFSupplementary MaterialPubReader   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.
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Original Articles
Clinical Study
Cross-Sectional and Longitudinal Examination of Insulin Sensitivity and Secretion across Puberty among Non-Hispanic Black and White Children
Shannon E. Marwitz, Megan V. Gaines, Sheila M. Brady, Sarah J. Mi, Miranda M. Broadney, Susan Z. Yanovski, Van S. Hubbard, Jack A. Yanovski
Endocrinol Metab. 2020;35(4):847-857.   Published online November 18, 2020
DOI: https://doi.org/10.3803/EnM.2020.771
  • 3,872 View
  • 85 Download
  • 8 Web of Science
  • 8 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Few studies using criterion measures of insulin sensitivity (SI) and insulin secretory capacity (ISC) have been conducted across puberty to adulthood. We examined how SI and ISC change from pre-puberty through adulthood.
Methods
Hyperglycemic clamp studies were performed in a convenience sample of non-Hispanic Black (NHB) and White children evaluated at age 6 to 12 years and at approximately 5-year intervals into adulthood (maximum age 27 years). SI and ISC (first-phase and steady-state insulin secretion) were determined cross-sectionally in 133 unique participants across puberty and in adulthood. Additionally, longitudinal changes in SI and ISC were compared at two timepoints among three groups defined by changes in pubertal development: pre-pubertal at baseline and late-pubertal at follow-up (n=27), early-pubertal at baseline and late-pubertal at follow-up (n=27), and late-pubertal at baseline and adult at follow-up (n=24).
Results
Cross-sectionally, SI was highest in pre-puberty and early puberty and lowest in mid-puberty (analysis of covariance [ANCOVA] P=0.001). Longitudinally, SI decreased from pre-puberty to late puberty (P<0.001), then increased somewhat from late puberty to adulthood. Cross-sectionally, first-phase and steady-state ISC increased during puberty and decreased in adulthood (ANCOVA P<0.02). Longitudinally, steady-state and first-phase ISC increased from pre-puberty to late puberty (P<0.007), and steady-state ISC decreased from late puberty to adulthood. The NHB group had lower SI (P=0.003) and greater first-phase and steady-state ISC (P≤0.001), independent of pubertal development.
Conclusion
This study confirms that SI decreases and ISC increases transiently during puberty and shows that these changes largely resolve in adulthood.

Citations

Citations to this article as recorded by  
  • Exploratory Longitudinal Analysis of the Circulating CHIT1 Activity in Pediatric Patients with Obesity
    Ioana Țaranu, Nicoleta Răcătăianu, Cristina Drugan, Cristina-Sorina Cătană, Andreea-Manuela Mirea, Diana Miclea, Sorana D. Bolboacă
    Children.2023; 10(1): 124.     CrossRef
  • Insulin Clearance in Health and Disease
    Sonia M. Najjar, Sonia Caprio, Amalia Gastaldelli
    Annual Review of Physiology.2023; 85(1): 363.     CrossRef
  • Influence of puberty on relationships between body composition and blood pressure: a cross-sectional study
    Esther A. Kwarteng, Lisa M. Shank, Loie M. Faulkner, Lucy K. Loch, Syeda Fatima, Suryaa Gupta, Hannah E. Haynes, Kaitlin L. Ballenger, Megan N. Parker, Sheila M. Brady, Anna Zenno, Marian Tanofsky-Kraff, Jack A. Yanovski
    Pediatric Research.2023; 94(2): 781.     CrossRef
  • Distribution of OGTT-Related Variables in Patients with Cystic Fibrosis from Puberty to Adulthood: An Italian Multicenter Study
    Andrea Foppiani, Fabiana Ciciriello, Arianna Bisogno, Silvia Bricchi, Carla Colombo, Federico Alghisi, Vincenzina Lucidi, Maria Ausilia Catena, Mariacristina Lucanto, Andrea Mari, Giorgio Bedogni, Alberto Battezzati
    Journal of Personalized Medicine.2023; 13(3): 469.     CrossRef
  • Fat-free/lean body mass in children with insulin resistance or metabolic syndrome: a systematic review and meta-analysis
    Diana Paola Córdoba-Rodríguez, Iris Iglesia, Alejandro Gomez-Bruton, Gerardo Rodríguez, José Antonio Casajús, Hernan Morales-Devia, Luis A. Moreno
    BMC Pediatrics.2022;[Epub]     CrossRef
  • Evaluating Triglyceride and Glucose Index as a Simple and Easy-to-Calculate Marker for All-Cause and Cardiovascular Mortality
    Kyung-Soo Kim, Sangmo Hong, You-Cheol Hwang, Hong-Yup Ahn, Cheol-Young Park
    Journal of General Internal Medicine.2022; 37(16): 4153.     CrossRef
  • An update of the consensus statement on insulin resistance in children 2010
    Veronica Maria Tagi, Sona Samvelyan, Francesco Chiarelli
    Frontiers in Endocrinology.2022;[Epub]     CrossRef
  • Dietary sugar restriction reduces hepatic de novo lipogenesis in boys with fatty liver disease
    Stephanie T. Chung, Sheela N. Magge
    Journal of Clinical Investigation.2021;[Epub]     CrossRef
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Clinical Study
Insulin Secretion and Insulin Resistance Trajectories over 1 Year after Kidney Transplantation: A Multicenter Prospective Cohort Study
Jun Bae Bang, Chang-Kwon Oh, Yu Seun Kim, Sung Hoon Kim, Hee Chul Yu, Chan-Duck Kim, Man Ki Ju, Byung Jun So, Sang Ho Lee, Sang Youb Han, Cheol Woong Jung, Joong Kyung Kim, Su Hyung Lee, Ja Young Jeon
Endocrinol Metab. 2020;35(4):820-829.   Published online November 18, 2020
DOI: https://doi.org/10.3803/EnM.2020.743
  • 4,716 View
  • 117 Download
  • 4 Web of Science
  • 5 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
We investigated the changing patterns of insulin secretion and resistance and risk factors contributing to the development of post-transplant diabetes mellitus (PTDM) in kidney recipients under tacrolimus-based immunosuppression regimen during 1 year after transplantation.
Methods
This was a multicenter prospective cohort study. Of the 168 subjects enrolled in this study, we analyzed a total 87 kidney transplant recipients without diabetes which was assessed by oral glucose tolerance test before transplantation. We evaluated the incidence of PTDM and followed up the index of insulin secretion (insulinogenic index [IGI]) and resistance (homeostatic model assessment for insulin resistance [HOMA-IR]) at 3, 6, 9 months, and 1 year after transplantation by oral glucose tolerance test and diabetes treatment. We also assessed the risk factors for incident PTDM.
Results
PTDM developed in 23 of 87 subjects (26.4%) during 1 year after transplantation. More than half of total PTDM (56.5%) occurred in the first 3 months after transplantation. During 1 year after transplantation, insulin resistance (HOMA-IR) was increased in both PTDM and no PTDM group. In no PTDM group, the increase in insulin secretory function to overcome insulin resistance was also observed. However, PTDM group showed no increase in insulin secretion function (IGI). Old age, status of prediabetes and episode of acute rejection were significantly associated with the development of PTDM.
Conclusion
In tacrolimus-based immunosuppressive drugs regimen, impaired insulin secretory function for reduced insulin sensitivity contributed to the development of PTDM than insulin resistance during 1 year after transplantation.

Citations

Citations to this article as recorded by  
  • Distúrbio do eixo hipotálamo-hipófise-gonadal e sua associação com resistência à insulina em receptores de transplante renal
    Lourdes Balcázar-Hernández, Victoria Mendoza-Zubieta, Baldomero González-Virla, Brenda González-García, Mariana Osorio-Olvera, Jesús Ubaldo Peñaloza-Juarez, Irene Irisson-Mora, Martha Cruz-López, Raúl Rodríguez-Gómez, Ramón Espinoza-Pérez, Guadalupe Varga
    Brazilian Journal of Nephrology.2023; 45(1): 77.     CrossRef
  • Hypothalamic-pituitary-gonadal axis disturbance and its association with insulin resistance in kidney transplant recipients
    Lourdes Balcázar-Hernández, Victoria Mendoza-Zubieta, Baldomero González-Virla, Brenda González-García, Mariana Osorio-Olvera, Jesús Ubaldo Peñaloza-Juarez, Irene Irisson-Mora, Martha Cruz-López, Raúl Rodríguez-Gómez, Ramón Espinoza-Pérez, Guadalupe Varga
    Brazilian Journal of Nephrology.2023; 45(1): 77.     CrossRef
  • Postoperative fasting plasma glucose and family history diabetes mellitus can predict post-transplantation diabetes mellitus in kidney transplant recipients
    Le Wang, Jin Huang, Yajuan Li, Kewei Shi, Sai Gao, Wangcheng Zhao, Shanshan Zhang, Chenguang Ding, Wei Gao
    Endocrine.2023; 81(1): 58.     CrossRef
  • Changes in glucose metabolism among recipients with diabetes 1 year after kidney transplant: a multicenter 1-year prospective study
    Jun Bae Bang, Chang-Kwon Oh, Yu Seun Kim, Sung Hoon Kim, Hee Chul Yu, Chan-Duck Kim, Man Ki Ju, Byung Jun So, Sang Ho Lee, Sang Youb Han, Cheol Woong Jung, Joong Kyung Kim, Hyung Joon Ahn, Su Hyung Lee, Ja Young Jeon
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • Pretransplant evaluation and the risk of glucose metabolic alterations after renal transplantation: a prospective study
    Arminda Fariña-Hernández, Domingo Marrero-Miranda, Estefania Perez-Carreño, Antonia De Vera-Gonzalez, Alejandra González, Cristian Acosta-Sorensen, Ana Elena Rodríguez-Rodríguez, Tatiana Collantes, Marta del Pino García, Ana Isabel Rodríguez-Muñoz, Carla
    Nephrology Dialysis Transplantation.2022;[Epub]     CrossRef
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Changes in Insulin Sensitivity and Insulin Secretory Function in Hyperthyroid Patients.
Dae Ho Lee, Min Young Chung, Yeon Jin Jang, Sang Sun Park, Eun Jin Choi, Ho Cheol Kang, Jae Hyun Cho, Tai Hee Lee
J Korean Endocr Soc. 1994;9(2):108-114.   Published online November 6, 2019
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  • 23 Download
AbstractAbstract PDF
The impairement of glucose metabolism is frequently associated in hyperthyroidism. The present study was performed to determine the effect of the thyroid hormone excess on insulin sensitivity and on insulin secretory function in vivo. Ten newly diagnosed hyperthyroid patients and fifteen healthy control subjects were subjected to frequently sampled intravenous glucose tolerance tests(FSIGT) after an overnight fast. Insulin sensitivity, represented by the insulin sensitivity index(S_1), was assessed by minimal model analysis of FSIGT data. Insulin secretion was measured by the total area under the insulin curve after glucose load.The results were as follows.1) The K_G values, which represent glucose tolerance, were not different between the hyperthyroid patients and the normals(2.2+-0.3 vs. 2.5+-0.3%/min, p>0.05).2) S_1 was significantly decreased in the hyperthyroid patients in comparison to the normals(7.5+-1.4 vs. 2.6+-0.3X10^-4 min^-1/uU/ml, p<0.05).3) The basal insulin concentration was higher in the hyperthyroid patients than in the normals(8.3+-2.4 vs. 4.6+-0.4 uU/ml, p=0.07). In addition, the insulin secretory response to a glucose load was increased in the hyperthyroid patients as evidenced by the peak plasma insulin level(168.2+-30.4 vs. 89.2+-13.9 uU/ml, p<0.05) and by the total area under the insulin curve(2641.1+-443.2 vs. 1696.7+-204.3 min uU/ml, p<0.05).These results clearly demonstrated that insulin sensitivity was impaired in these newly diagnosed hyperthyroid patients. However, glucose tolerance was maintained by the increased insulin secretion.
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Clinical Study
C-Peptide-Based Index Is More Related to Incident Type 2 Diabetes in Non-Diabetic Subjects than Insulin-Based Index
Jong-Dai Kim, Sung Ju Kang, Min Kyung Lee, Se Eun Park, Eun Jung Rhee, Cheol-Young Park, Ki-Won Oh, Sung-Woo Park, Won-Young Lee
Endocrinol Metab. 2016;31(2):320-327.   Published online June 21, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.2.320
  • 4,911 View
  • 83 Download
  • 45 Web of Science
  • 44 Crossref
AbstractAbstract PDFPubReader   
Background

Diabetes can be efficiently prevented by life style modification and medical therapy. So, identification for high risk subjects for incident type 2 diabetes is important. The aim of this study is to identify the best β-cell function index to identify high risk subjects in non-diabetic Koreans.

Methods

This is a retrospective longitudinal study. Total 140 non-diabetic subjects who underwent standard 2-hour 75 g oral glucose tolerance test from January 2007 to February 2007 at Kangbuk Samsung Hospital and followed up for more than 1 year were analyzed (mean follow-up, 54.9±16.4 months). The subjects were consist of subjects with normal glucose tolerance (n=44) and subjects with prediabetes (n=97) who were 20 years of age or older. Samples for insulin and C-peptide levels were obtained at 0 and 30 minutes at baseline.

Results

Thirty subjects out of 140 subjects (21.4%) developed type 2 diabetes. When insulin-based index and C-peptide-based index are compared between progressor and non-progressor to diabetes, all C-peptide-based indices were statistically different between two groups, but only insulinogenic index and disposition index among insulin-based index were statistically different. C-peptide-based index had higher value of area under receiver operating characteristic curve (AROC) value than that of insulin-based index. "C-peptidogenic" index had highest AROC value among indices (AROC, 0.850; 95% confidence interval, 0.761 to 0.915). C-peptidogenic index had significantly higher AROC than insulinogenic index (0.850 vs. 0.731 respectively; P=0.014).

Conclusion

C-peptide-based index was more closely related to incident type 2 diabetes in non-diabetic subjects than insulin-based index.

Citations

Citations to this article as recorded by  
  • Insulinogenic index and early phase insulin secretion predict increased risk of worsening glucose tolerance and of cystic fibrosis-related diabetes
    Kathryn J. Potter, Valérie Boudreau, Anne Bonhoure, François Tremblay, Annick Lavoie, Maité Carricart, Peter A. Senior, Rémi Rabasa-Lhoret
    Journal of Cystic Fibrosis.2023; 22(1): 50.     CrossRef
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    Gianfranco Di Giuseppe, Gea Ciccarelli, Laura Soldovieri, Umberto Capece, Chiara M.A. Cefalo, Simona Moffa, Enrico C. Nista, Michela Brunetti, Francesca Cinti, Antonio Gasbarrini, Alfredo Pontecorvi, Andrea Giaccari, Teresa Mezza
    Trends in Endocrinology & Metabolism.2023; 34(4): 216.     CrossRef
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    Anuj Maheshwari
    IP Journal of Nutrition, Metabolism and Health Science.2023; 6(2): 63.     CrossRef
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    Marie-Therese Weiser-Fuchs, Elena Maggauer, Mireille N. M. van Poppel, Bence Csapo, Gernot Desoye, Harald C. Köfeler, Andrea Groselj-Strele, Slave Trajanoski, Herbert Fluhr, Barbara Obermayer-Pietsch, Evelyn Jantscher-Krenn
    Nutrients.2023; 15(18): 4042.     CrossRef
  • Elevated Peripheral Brain-Derived Neurotrophic Factor Level Associated With Decreasing Insulin Secretion May Forecast Memory Dysfunction in Patients With Long-Term Type 2 Diabetes
    Xi Huang, Zuolin Xie, Chenchen Wang, Shaohua Wang
    Frontiers in Physiology.2022;[Epub]     CrossRef
  • Predictors of Glycemic Outcomes at 1 Year Following Pediatric Total Pancreatectomy With Islet Autotransplantation
    Sarah E. Swauger, Lindsey N. Hornung, Deborah A. Elder, Appakalai N. Balamurugan, David S. Vitale, Tom K. Lin, Jaimie D. Nathan, Maisam Abu-El-Haija
    Diabetes Care.2022; 45(2): 295.     CrossRef
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    Violeta Raverdy, Ricardo V Cohen, Robert Caiazzo, Helene Verkindt, Tarissa Beatrice Zanata Petry, Camille Marciniak, Benjamin Legendre, Pierre Bauvin, Estelle Chatelain, Alain Duhamel, Elodie Drumez, Naima Oukhouya-Daoud, Mikael Chetboun, Gregory Baud, Em
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    Hye Eun Cho, Seung Bum Yang, Mi Young Gi, Ju Ae Cha, so Young Park, Hyun Yoon
    Endocrine Research.2022; 47(2): 80.     CrossRef
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    Breastfeeding Medicine.2022; 17(7): 566.     CrossRef
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    Teodora Beljić-Živković
    Galenika Medical Journal.2022; 1(1): 57.     CrossRef
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    Ernesto Maddaloni, Geremia B. Bolli, Brian M. Frier, Randie R. Little, Richard D. Leslie, Paolo Pozzilli, Raffaela Buzzetti
    Diabetes, Obesity and Metabolism.2022; 24(10): 1912.     CrossRef
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    Sara Sokooti, Wendy A. Dam, Tamas Szili-Torok, Jolein Gloerich, Alain J. van Gool, Adrian Post, Martin H. de Borst, Ron T. Gansevoort, Hiddo J. L. Heerspink, Robin P. F. Dullaart, Stephan J. L. Bakker
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    Racha Ghoussaini, Hani Tamim, Martine Elbejjani, Maha Makki, Lara Nasreddine, Hussain Ismaeel, Mona P. Nasrallah, Nathalie K. Zgheib
    Frontiers in Endocrinology.2022;[Epub]     CrossRef
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    Gert Wensvoort
    Medical Hypotheses.2022; 168: 110964.     CrossRef
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    Qi Jin, Ni Shi, Desmond Aroke, Dong Hoon Lee, Joshua J. Joseph, Macarius Donneyong, Darwin L. Conwell, Phil A. Hart, Xuehong Zhang, Steven K. Clinton, Zobeida Cruz-Monserrate, Theodore M. Brasky, Rebecca Jackson, Lesley F. Tinker, Simin Liu, Lawrence S. P
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    Clive J Petry, Keith A Burling, Peter Barker, Ieuan A Hughes, Ken K Ong, David B Dunger
    The Journal of Clinical Endocrinology & Metabolism.2021; 106(6): e2413.     CrossRef
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  • Plasma C-Peptide and Risk of Developing Type 2 Diabetes in the General Population
    Sara Sokooti, Lyanne M. Kieneker, Martin H. de Borst, Anneke Muller Kobold, Jenny E. Kootstra-Ros, Jolein Gloerich, Alain J. van Gool, Hiddo J. Lambers Heerspink, Ron T Gansevoort, Robin P.F. Dullaart, Stephan J. L. Bakker
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  • Effect of Anthocyanins Supplementation on Serum IGFBP-4 Fragments and Glycemic Control in Patients with Fasting Hyperglycemia: A Randomized Controlled Trial


    Liping Yang, Zhaomin Liu, Wenhua Ling, Li Wang, Changyi Wang, Jianping Ma, Xiaolin Peng, Jianying Chen
    Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2020; Volume 13: 3395.     CrossRef
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    Britta Wessels, Julius Honecker, Theresa Schöttl, Lynne Stecher, Martin Klingenspor, Hans Hauner, Thomas Skurk
    Obesity.2019; 27(5): 756.     CrossRef
  • Higher Plasma Level of Nampt Presaging Memory Dysfunction in Chinese Type 2 Diabetes Patients with Mild Cognitive Impairment
    Xi Huang, Chenchen Wang, Sai Tian, Rong Huang, Dan Guo, Haoqiang Zhang, Jijing Shi, Shaohua Wang
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  • Increased Ratio of Global O-GlcNAcylation to Tau Phosphorylation at Thr212 Site Is Associated With Better Memory Function in Patients With Type 2 Diabetes
    Rong Huang, Sai Tian, Jing Han, Rongrong Cai, Hongyan Lin, Dan Guo, Jiaqi Wang, Shaohua Wang
    Frontiers in Physiology.2019;[Epub]     CrossRef
  • Pancreatic fat content is associated with β-cell function and insulin resistance in Chinese type 2 diabetes subjects
    Ting Lu, Yao Wang, Ting Dou, Bizhen Xue, Yuanyuan Tan, Jiao Yang
    Endocrine Journal.2019; 66(3): 265.     CrossRef
  • Effectiveness of Eriomin® in managing hyperglycemia and reversal of prediabetes condition: A double‐blind, randomized, controlled study
    Carolina B. Ribeiro, Fernanda M. Ramos, John A. Manthey, Thais B. Cesar
    Phytotherapy Research.2019; 33(7): 1921.     CrossRef
  • Association between plasma adipsin level and mild cognitive impairment in Chinese patients with type 2 diabetes: a cross-sectional study
    Dan Guo, Yang Yuan, Rong Huang, Sai Tian, Jiaqi Wang, Hongyan Lin, Ke An, Jin Han, Shaohua Wang
    BMC Endocrine Disorders.2019;[Epub]     CrossRef
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    Bernd Richter, Bianca Hemmingsen, Maria-Inti Metzendorf, Yemisi Takwoingi
    Cochrane Database of Systematic Reviews.2018;[Epub]     CrossRef
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    Hongmei Zhang, Bingxian Bian, Fan Hu, Qing Su
    Oncotarget.2017; 8(31): 51786.     CrossRef
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    Won-Young Lee
    Endocrinology and Metabolism.2017; 32(1): 62.     CrossRef
  • Obesity Influence on Insulin Activity and Resting Metabolic Rate in Type 2 Diabetes
    Rodica Doros, Daniela Lixandru, Laura Petcu, Ariana Picu, Manuela Mitu, Janeta Tudosoiu, Constantin Ionescu-Tîrgoviste
    Romanian Journal of Diabetes Nutrition and Metabolic Diseases.2016; 23(4): 377.     CrossRef
  • Insulin Secretory Capacity and Insulin Resistance in Korean Type 2 Diabetes Mellitus Patients
    Jong-Dai Kim, Won-Young Lee
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  • Prediction of Diabetes Using Serum C-Peptide
    Hye Seung Jung
    Endocrinology and Metabolism.2016; 31(2): 275.     CrossRef
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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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AbstractAbstract PDFPubReader   
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.

Citations

Citations to this article as recorded by  
  • 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
    Scientific Reports.2019;[Epub]     CrossRef
  • 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
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The Change of Insulin Sensitivity and Insulin Secretion According to Glucose Metabolism Status in Patients with Cushing's Syndrome.
In Kyung Jeong, Sung Hoon Kim, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Hyung Joon Yoo, Kyu Jeong Ahn, Jung Hynun Noh, Dong Jun Kim, Kwang Won Kim
J Korean Endocr Soc. 2003;18(4):392-403.   Published online August 1, 2003
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AbstractAbstract PDF
BACKGROUND
Glucocorticoid plays an important role in the control of carbohydrate metabolism. Patients with Cushing's syndrome have been reported to have an increased incidence of carbohydrate intolerance due to peripheral insulin resistance and hyperinsulinemia, although the exact incidence and nature of this disorder have remained unclear. Few results have been published about insulin resistance and insulin secretion according to the level of glucose concentration, or about the reversibility of such defects in patients with Cushing's syndrome. METHODS: To assess the effect of glucocorticoid on the insulin sensitivity and insulin secretion in Cushing's syndrome, 15 patients with Cushing's syndrome were classified into 3 groups (normal glucose tolerance: NGT, impaired glucose tolerance: IGT, diabetes: DM) according to the degree of glucose tolerance based on the oral glucose tolerance test (OGTT). Insulin modified, frequentlysampled, intravenous glucose tolerance test (FSIGT) was performed before and after curative surgery on these patients and on 15 healthy control subjects. Data were evaluated by non-parametric statistical analysis. RESULTS: 1) Among the 15 patients with Cushing's syndrome, 3 (20%) were NGT, 4 (27%) IGT, and 8 (53%) DM, based on OGTT. Twenty-four hour urinary free cortisol (UFC) was significantly higher in the DM group. 2) Insulin sensitivity index (SI) of Cushing's syndrome was significantly lower than that of the control group (P=0.0024), but was not significantly different among the three Cushing's syndrome groups of NGT, IGT and DM. 3) Glucose mediated glucose disposal (SG) (Ed- confirm this abbreviation; it does not seem to match the definition) of Cushing's syndrome was not significantly different from that of the control group. 4) Insulin secretion (AIRg) of Cushing's syndrome tended to be high, but it was not significantly different from that of control. However, according to the level of glucose concentration there was significant difference in AlRg among the three Cushing's syndrome groups (P=0.0031); AIRg of DM was significantly lower than that of NGT. 5) After surgical treatment, parameters of insulin sensitivity and insulin secretion were normalized in 6 cured patients; 1 with NGT, 1 with IGT, and 4 with DM, preoperatively. Median SI of all 6 patients was significantly improved up to the normal range postoperatively (P=0.0022). Median AIRg of these 6 patients was balanced around that of normal control postoperatively (P=0.0286). CONCLUSION: Eighty percent of patients with Cushing's syndrome had abnormality of carbohydrate metabolism. Insulin sensitivity was significantly decreased in Cushing's syndrome. Insulin secretion was significantly higher only in the NGT and IGT groups of Cushing's syndrome. As the hypercortisolemia is exacerbated, insulin secretion is significantly decreased and causes DM, suggesting that glucocorticoid has a direct or indirect toxic effect on the pancreatic beta cell.
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Search for "Proximal Histidine" of Thyroperoxidase Using Site Directed Mutagenesis.
Won Bae Kim, Young Kee Shong
J Korean Endocr Soc. 2003;18(4):371-378.   Published online August 1, 2003
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BACKGROUND
Thyroperoxidase (TPO), a transmembrane heme containing glycoprotein, catalyzes iodide organification and thyroid hormone synthesis. It is a single peptide making a loop with more than one disulfide bond. The tertiary conformational structure is essential for its enzymatic activity and immunogenicity. The proximal histidine is thought to play a major role in enzymatic activity since it is linked to the iron center of the heme. The crystal structure of TPO has not yet been reported, but some have suggested histidine 407 be a putative proximal histidine based on comparison of a.a. sequence for TPO and that for myeloperoxidase. METHODS: The putative histidine 407 and nearby histidine 414 were mutated to arginine to verify their role as the proximal histidine. Using site directed mutagenesis of wild type, human TPO cDNA, mutants H407R and H414R were made. Mutant cDNAs were transiently transfected into COS-7 cells, and the TPO enzyme activities were measured by guaiacol assay. Four cysteine residues around the putative proximal histidines were mutated to serine and their enzymatic activities were measured to check if they were involved in the formation of intra-molecular disulfide bonds. RESULTS: TPO protein expression of H407R- and H414R- transfected cells was confirmed by Western blot, using Hashimoto's IgG as primary antibody. Both the mutants H407R and H414R showed significant peroxidase enzymatic activity, although lower than those of the wild type. None of the cysteine mutants, C375S, C389S, C598S, and C655S, were detected by Hashimoto's IgG ordisplayed any enzymatic activity. CONCLUSION: These data suggest that neither histidine 407 nor histidine 414 functions as the "proximal histidine" in human TPO. All the cysteine residues checked (375, 389, 598, 655) might be involved in the formation of disulfide bonds in TPO molecules, but this hypothesis could not be confirmed. A further search for the other putative histidine residues using the same strategy is needed to define the structure-function relationship in the human TPO molecule.
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The Effects of Aging on the Proliferation and Differentiation of Osteoblasts from Human Mesenchymal Stem Cells.
Ki Hyun Baek, Hyun Jung Tae, Ki Won Oh, Won Young Lee, Chung Kee Cho, Soon Yong Kwon, Moo Il Kang, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang, Choon Choo Kim
J Korean Endocr Soc. 2003;18(3):296-305.   Published online June 1, 2003
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AbstractAbstract PDF
BACKGROUND
Osteoblasts originate from osteoprogenitor cells in bone marrow stroma, termed mesenchymal stem cells (MSCs) or bone marrow stromal cells. Each MSC forms colonies (colony forming units-fibroblasts [CFU-Fs]) when cultured ex vivo. There are some reports about the age-related changes of the number and osteogenic potential of osteoprogenitor cells, but any relationship has not been clearly established in humans. In this study, we counted MSCs using CFU-Fs count and examined the proliferative capacity and differentiation potential of osteoprogenitor cells. Finally, we analyzed how these parameters varied with donor age. METHODS: Bone marrow was obtained from the iliac crest of young (n=6, 27.2+/-8.6 years old) and old (n=10, 57.4+/-6.7 years old) healthy donors. Mononuclear cells, including MSCs, were isolated and cultured in osteogenic medium. In primary culture, we compared the colony-forming efficiency of MSCs between the two groups and determined the matrix calcification. When primary culture showed near confluence, the cells were subcultured. Alkaline phosphatase activity, osteocalcinexpression by RT-PCR and proliferative potential by MTT assay were examined by the time course of secondary culture. RESULTS: At the 15th day of primary culture, the mean number of CFU-Fs was significantly higher in the younger donors (young: 148.3+/-28.9, old: 54.3+/-9.1, p=0.02) and the mean size of CFU-Fs was also larger in the younger donors than the older donors. However, matrix calcification was not different between the two groups (young: 103.6+/-50.6, old: 114.0+/-56.5, p=NS). In secondary culture, alkaline phosphatase activities were significantly lower in the older donors. The younger donors showed peak alkaline phosphatase activity at day 10, while the older donors didn't showed a remarkable peak (young: 935.5+/-115.0U/mg, old: 578.4+/-115.7U/mg, p<0.05). Total cell number as a proliferative index increased progressively during the secondary culture and a significantly greater cell number was noted in the younger donors. Osteocalcin expression was generally upregulated in the younger donors, but this was not statistically significant. CONCLUSION: Our study shows that the number of osteoprogenitor cells is decreased during aging and that the proliferative capacity and differentiation potential of osteoprogenitor cells seem to be reduced during aging.
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Glucose metabolism in chronic hepatitis B infection-acute insulin response and glucose disappearance rate to intravenous glucose.
Chan Soo Shin, Kyoung Soo Park, Seong Yeon Kim, Hong Kyu Lee, Chang Soon Koh, Young Bae Kim
J Korean Endocr Soc. 1997;12(2):275-282.   Published online January 1, 2001
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AbstractAbstract PDF
BACKGROUND
Glucose intolerance and diabetes mellitus are frequently observed in chronic liver disease. However, the causal relationships between these two are difficult to prove. Chronic hepatitis B infection, which is prevalent in Korea, is thought to be a good model to study the natural history of abnormal glucose metabolism in chronic liver disease because many patients with chronic hepatitis B infection eventually progress to liver cirrhosis. METHODS: In order to evaluate glucose metabolism in chronic hepatitis B infection, we did intravenous glucose tolerance test in patients with chronic hepatitis B and age, sex and body mass index matched controls and compared the first phase insulin response and glucose disappearance rates between 2 groups. RESULTS: Patients with chronic hepatitis B showed lower glucose disappearance rate and higher plasma insulin and C-peptide area (0-10min after iv glucose) than controls. Patients with decreased glucose disappearance rate had higher AST level and decreased plasma C-peptide area (0-10min). CONCLUSION: Most of the patients with chronic hepatits B infection is associated with insulin resistance and compensatory increase in the first phase insulin secretion. Inadequate insulin secretion may contribute to decreased glucose disappearance rate in these patients.
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