Pathologic Changes and Glucose Homeostasis According to Expression of Human Islet Amyloid Polypeptide in Type 2 Diabetic Patients

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  • Ji Young Park
    Division of Endocrinology and Metabolism (JYP, SHO, SYK, SWK, JHC, YKM, M-SL, MKL, JHK, K-WK), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
  • Hee Sung No
    Samsung Biomedical Research Institute, Seoul, South Korea (HSN, YRA, YSK)
  • You Ran Ahn
    Samsung Biomedical Research Institute, Seoul, South Korea (HSN, YRA, YSK)
  • Seung Hoon Oh
    Division of Endocrinology and Metabolism (JYP, SHO, SYK, SWK, JHC, YKM, M-SL, MKL, JHK, K-WK), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
  • Young Seok Kim
    Samsung Biomedical Research Institute, Seoul, South Korea (HSN, YRA, YSK)
  • Sook Young Kim
    Division of Endocrinology and Metabolism (JYP, SHO, SYK, SWK, JHC, YKM, M-SL, MKL, JHK, K-WK), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
  • Kee Taek Jang
    Division of Pathology (KTJ), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
  • Sun Wook Kim
    Division of Endocrinology and Metabolism (JYP, SHO, SYK, SWK, JHC, YKM, M-SL, MKL, JHK, K-WK), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
  • Jae Hoon Chung
    Division of Endocrinology and Metabolism (JYP, SHO, SYK, SWK, JHC, YKM, M-SL, MKL, JHK, K-WK), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
  • Yong Ki Min
    Division of Endocrinology and Metabolism (JYP, SHO, SYK, SWK, JHC, YKM, M-SL, MKL, JHK, K-WK), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
  • Jin Seok Heo
    Division of Surgery (JSH, SHC, DWC), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
  • Seong Ho Choi
    Division of Surgery (JSH, SHC, DWC), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
  • Dong Wook Choi
    Division of Surgery (JSH, SHC, DWC), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
  • Myung-Shik Lee
    Division of Endocrinology and Metabolism (JYP, SHO, SYK, SWK, JHC, YKM, M-SL, MKL, JHK, K-WK), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
  • Moon Kyu Lee
    Division of Endocrinology and Metabolism (JYP, SHO, SYK, SWK, JHC, YKM, M-SL, MKL, JHK, K-WK), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
  • Jae Hyeon Kim
    Division of Endocrinology and Metabolism (JYP, SHO, SYK, SWK, JHC, YKM, M-SL, MKL, JHK, K-WK), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
  • Kwang-Won Kim
    Division of Endocrinology and Metabolism (JYP, SHO, SYK, SWK, JHC, YKM, M-SL, MKL, JHK, K-WK), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

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<jats:p> The amount of amyloid detectable in islets varies, and is not always correlated with degree of β-cell loss. It has been hypothesized that islet amyloid polypeptide (IAPP) aggregation causes β-cell dysfunction. In this study, we investigated the relationship between IAPP expression and glucose homeostasis in pancreatectomized patients. Human pancreatic head tissues were collected from 46 pancreatic tumor patients. We divided the diabetic cases into two groups, patients with higher IAPP–expressing islets (DM-H) and patients with lower IAPP–expressing islets (DM-L), and compared both groups to patients with normal glucose tolerance (NGT). Interestingly, oral glucose tolerance test analyses showed that DM-L patients had significantly higher glucose levels and lower C-peptide levels than DM-H patients. Furthermore, the DM-H group showed a relative β-cell volume similar to that of the NGT group, as well as a significantly higher relative β-cell volume than the DM-L group. The DM-L group was significantly higher than the DM-H group, not only in the rates of replication and apoptosis, but also in the nuclear C/EBP homologous protein and the ratio of oligomer to IAPP. Thus, IAPP expression may not be an indicator of cell death induction. IAPP, including oligomer, may be an important determinant in the fate of islet β-cells. This manuscript contains online supplemental material at http://www.jhc.org . Please visit this article online to view these materials. </jats:p>

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