Estimated proinsulin processing activity of prohormone convertase (PC) 1/3 rather than PC2 is decreased in pancreatic β-cells of type 2 diabetic patients
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- Ozawa Sachihiko
- Third Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, Tokyo 181-8611, Japan
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- Katsuta Hidenori
- Third Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, Tokyo 181-8611, Japan
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- Suzuki Kiyoshi
- Division of Clinical Laboratory, Shimada Municipal Hospital, Shizuoka 427-8501, Japan
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- Takahashi Kazuto
- Third Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, Tokyo 181-8611, Japan
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- Tanaka Toshiaki
- Third Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, Tokyo 181-8611, Japan
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- Sumitani Yoshikazu
- Third Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, Tokyo 181-8611, Japan
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- Nishida Susumu
- Third Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, Tokyo 181-8611, Japan
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- Yoshimoto Katsuhiko
- Third Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, Tokyo 181-8611, Japan
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- Ishida Hitoshi
- Third Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, Tokyo 181-8611, Japan
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抄録
Type 2 diabetic (T2D) patients exhibit fasting relative hyperproinsulinemia owing to pancreatic β-cell dysfunction. To clarify the mechanism underlying this hyperproinsulinemic state, we evaluated the activities of the endopeptidases prohormone convertase (PC) 1/3 and PC2 in T2D patients. Fasting blood levels of intact proinsulin (IPI), total proinsulin (t-PI) and C-peptide were measured simultaneously, and intravenous glucagon loading was performed to investigate the dynamics of circulating proinsulin-related molecules released from pancreatic β-cells in 12 healthy volunteers and 18 T2D patients. Taking advantage of the 95% cross-reactivity between proinsulin and des-31,32-proinsulin (des-31,32-PI) with the human proinsulin radioimmunoassay kit used in this study, we estimated PC1/3 and PC2 activities using the following formulas: des-31,32-PI = (t-PI–IPI)/0.95; PC1/3 activity = des-31,32-PI/IPI; and PC2 activity = C-peptide/des-31,32-PI. C-peptide responses to glucagon were slightly lower among T2D patients. IPI and the IPI/C-peptide ratio were significantly higher in T2D patients (p<0.05 and p<0.01, respectively). There was no difference in des-31,32-PI levels or PC2 activity between the two groups. However, PC1/3 activity was significantly lower in T2D patients than in the control group (p<0.01). We propose that decreased activity of PC1/3 rather than PC2 in pancreatic β-cells is involved in the impaired proinsulin processing, resulting in elevated IPI levels in T2D patients.
収録刊行物
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- Endocrine Journal
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Endocrine Journal 61 (6), 607-614, 2014
一般社団法人 日本内分泌学会
