Loss of beta-cells with fibrotic islet destruction in type 2 diabetes mellitus.
Recent morphologic analyses of human pancreases strongly suggest that a decreased beta-cell mass is observed from the early stages of diabetes and is caused by accelerated apoptosis of the beta-cells. In this article, we propose that fibrotic islet destruction might be one of the important pathogenic mechanisms of the limited capacity of beta-cell proliferation and accelerated apoptosis in diabetic patients. We have found that pancreatic stellate cells (PSCs) are involved in the progression of islet fibrosis in type 2 diabetes. High concentrations of glucose and insulin in islets contribute to PSC activation and proliferation through angiotensin II type 2 (ATII) signaling pathway, although the exact mechanisms remain to be confirmed. Angiotensin-converting enzyme inhibitors attenuate fibrotic islet destructions and that these have some beneficial effects on glucose tolerance. We suggest that PSCs might play a major role for the fibrotic islet destruction in patients with type 2 diabetes, and suppression of PSCs activation and proliferation might be one of the reasonable target to prevent and delay the progression of the type 2 diabetes mellitus.
Kim
Ji-Won
JW
Department of Endocrinology and Metabolism, The Catholic University of Korea, Seoul, Korea.
Ko
Seung-Hyun
SH
Cho
Jae-Hyoung
JH
Sun
Chenglin
C
Hong
Oak-kee
OK
Lee
Seung-Hwan
SH
Kim
Ji-Hyun
JH
Lee
Kang-Woo
KW
Kwon
Hyuk-Sang
HS
Lee
Jung-Min
JM
Song
Ki-Ho
KH
Son
Ho-Young
HY
Yoon
Kun-Ho
KH
D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D005355:Fibrosis; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D007515:Islets of Langerhans / Q000473:pathology*; D010179:Pancreas / Q000033:anatomy & histology / Q000473:pathology / Q000503:physiopathology; D012016:Reference Values
D007328:Insulin