Diabetes Research and Clinical Practice, 0
1992 Elsevier
Science Publishers
15 (1992) 15-16 B.V. All rights reserved
15
016%8227/92/$05.00
DIABET 00578
Relationship between islet amyloid polypeptide (IAPP) deposition and insulin response and P-cell volume in diabetes mellitus Tetsuro Kobayashi, Yuriko Ito, Koji Nakanish, Kazuhiko Sugawara, Minoru Okubo, Tadao Sugimoto, Toshio Murase and Kinori Kosaka Department
of Endocrinology
and Metabolism,
Toranomon Hospital and Okinaka Memorial Institute for Medical Research,
Toranomon. Minato-ku. Tokyo. Japan
Key words: Islet amyloid polypeptide (IAPP); Non-insulin-dependent cirrhosis; Hyperinsulinemia
A possible relationship between islet amyloid polypeptide (IAPP)-positive amyloid deposition and insulin response and B-cell volume was examined in patients with non-insulin-dependent diabetes mellitus (NIDDM) and in diabetics with liver cirrhosis. Seven patients with non-insulindependent diabetes mellitus (NIDDM) (mean age: 68 years, M/F: 4/3, mean duration of diabetes: 6.6 years) and 12 diabetics with liver cirrhosis (mean age: 59 years, M/F: 8/4, mean duration of diabetes: 9.1 years), who had serum immunoreactive insulin (IRI) data within 3 years of their death, were included in this study. Pancreatic tissue sections were stained immunohistochemicahy for IAPP and the volume of p-cells was analyzed by computer-assisted morphometry. The value of IAPP deposition and p-cell volume were calculated as follows: (1) Correspondence
to: T. Kobayashi, Dept. of Endocrinology and Metabolism, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo 105, Japan.
diabetes mellitus (NIDDM);
Liver
IAPP area in the pancreas: IAPP/islet = freislet x IAPP area in the quency of IAPP’ islet/area of the islet; (2) p-cell area in the pancreas: /?-cell/pancreas = /.&cell area in the islet/area of pancreas; (3) IAPP area, p-cell area, area of the islet and area of the pancreas were mean values calculated from 25 photographs in each case. Frequencies of pancreatic IAPP were 57% (4/7) in NIDDM patients and 757, (9/12) in diabetics with liver cirrhosis. A negative association was observed between IAPP/islet and the integrated value of IRI (EIRI) during a 100-g oral glucose tolerance test (OGTT), (CIRI)/integrated value of blood glucose (BG) value during OGTT (I;BG): (CIRI/XBG) in NIDDM (I = -0.92, P < 0.05). A negative association was also observed between IAPP/pancreas and P-cell pancreas in NIDDM (r = - 0.65, P < 0.05). A negative association between IAPP deposition and /?-cell volume and IRI response tended to be present in diabetics with liver cirrhosis. The IRI response in diabetics with liver cirrhosis was
16
significantly higher than that in patients with NIDDM. IAPP was stained immunohistochemitally in P-cell cytoplasm as well as in islet amyloid in diabetic cases with liver cirrhosis, while IAPP was not stained in /?-cell cytoplasm in NIDDM. It was observed that IAPP deposition was inversely related to insulin response and also to P-cell volume in NIDDM. It may, therefore, be possible that the impaired insulin response in NIDDM is partly related to IAPP’ amyloid deposition over the islet. Moreover, insulin secreted from /?-cells may be interrupted and
p-cells may be disrupted by amyloid surrounding the islet. The presence of IAPP immunoreactivity in /?-cell cytoplasm in diabetics with liver cirrhosis may suggest a hyperproduction of IAPP as well as insulin in this pathological condition.
Acknowledgements We would like to acknowledge MS M. Shibata and F. Takano for their excellent secretarial help.
1992 Elsevier
Science Publishers
15 (1992) 15-16 B.V. All rights reserved
15
016%8227/92/$05.00
DIABET 00578
Relationship between islet amyloid polypeptide (IAPP) deposition and insulin response and P-cell volume in diabetes mellitus Tetsuro Kobayashi, Yuriko Ito, Koji Nakanish, Kazuhiko Sugawara, Minoru Okubo, Tadao Sugimoto, Toshio Murase and Kinori Kosaka Department
of Endocrinology
and Metabolism,
Toranomon Hospital and Okinaka Memorial Institute for Medical Research,
Toranomon. Minato-ku. Tokyo. Japan
Key words: Islet amyloid polypeptide (IAPP); Non-insulin-dependent cirrhosis; Hyperinsulinemia
A possible relationship between islet amyloid polypeptide (IAPP)-positive amyloid deposition and insulin response and B-cell volume was examined in patients with non-insulin-dependent diabetes mellitus (NIDDM) and in diabetics with liver cirrhosis. Seven patients with non-insulindependent diabetes mellitus (NIDDM) (mean age: 68 years, M/F: 4/3, mean duration of diabetes: 6.6 years) and 12 diabetics with liver cirrhosis (mean age: 59 years, M/F: 8/4, mean duration of diabetes: 9.1 years), who had serum immunoreactive insulin (IRI) data within 3 years of their death, were included in this study. Pancreatic tissue sections were stained immunohistochemicahy for IAPP and the volume of p-cells was analyzed by computer-assisted morphometry. The value of IAPP deposition and p-cell volume were calculated as follows: (1) Correspondence
to: T. Kobayashi, Dept. of Endocrinology and Metabolism, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo 105, Japan.
diabetes mellitus (NIDDM);
Liver
IAPP area in the pancreas: IAPP/islet = freislet x IAPP area in the quency of IAPP’ islet/area of the islet; (2) p-cell area in the pancreas: /?-cell/pancreas = /.&cell area in the islet/area of pancreas; (3) IAPP area, p-cell area, area of the islet and area of the pancreas were mean values calculated from 25 photographs in each case. Frequencies of pancreatic IAPP were 57% (4/7) in NIDDM patients and 757, (9/12) in diabetics with liver cirrhosis. A negative association was observed between IAPP/islet and the integrated value of IRI (EIRI) during a 100-g oral glucose tolerance test (OGTT), (CIRI)/integrated value of blood glucose (BG) value during OGTT (I;BG): (CIRI/XBG) in NIDDM (I = -0.92, P < 0.05). A negative association was also observed between IAPP/pancreas and P-cell pancreas in NIDDM (r = - 0.65, P < 0.05). A negative association between IAPP deposition and /?-cell volume and IRI response tended to be present in diabetics with liver cirrhosis. The IRI response in diabetics with liver cirrhosis was
16
significantly higher than that in patients with NIDDM. IAPP was stained immunohistochemitally in P-cell cytoplasm as well as in islet amyloid in diabetic cases with liver cirrhosis, while IAPP was not stained in /?-cell cytoplasm in NIDDM. It was observed that IAPP deposition was inversely related to insulin response and also to P-cell volume in NIDDM. It may, therefore, be possible that the impaired insulin response in NIDDM is partly related to IAPP’ amyloid deposition over the islet. Moreover, insulin secreted from /?-cells may be interrupted and
p-cells may be disrupted by amyloid surrounding the islet. The presence of IAPP immunoreactivity in /?-cell cytoplasm in diabetics with liver cirrhosis may suggest a hyperproduction of IAPP as well as insulin in this pathological condition.
Acknowledgements We would like to acknowledge MS M. Shibata and F. Takano for their excellent secretarial help.
