Selective beta-cell loss and alpha-cell expansion in patients with type 2 diabetes mellitus in Korea.
In the presence of obesity, beta-cell mass needs to be increased to compensate for the accompanying demands and maintain euglycemia. However, in Korea, the majority of type 2 diabetic patients are nonobese. We determined the absolute masses, relative volumes, and ratio of alpha- and beta-cell in the pancreas and islets in normal and diabetic Korean subjects to correlate these findings with the clinical characteristics. Whole pancreases procured from organ donors were divided into 24 parts (control 1, n = 9). Tissue was also obtained by surgical resection after 35 partial pancreatectomies: in 25 diabetic patients, 10 age- and body mass index (BMI)-matched patients of benign or malignant pancreatic tumor without diabetes mellitus (DM) (control 2). Morphometric quantifications were performed. In control 1, the relative volume of beta-cells was 2.1 +/- 0.9%, and the total beta-cell mass was 1.3 +/- 0.3 g. The relative volume of beta-cells was found to be variable (control 1, 2.1 +/- 0.9%; control 2, 1.9 +/- 0.7%; DM, 1.4 +/- 1.0%; P < 0.05 DM vs. control 1 and 2) and showed good correlation with BMI (control 1, r(2) = 0.64; DM, r(2) = 0.55; all subjects, r(2) = 0.38; P < 0.05). Notably, in type 2 diabetic patients, the ratio of alpha-cell area to beta-cell area in the islet was higher than in control 1 and 2 (0.81 +/- 0.4 vs. 0.29 +/- 0.2, 0.20 +/- 0.1, P < 0.05). Additionally, significant alpha-cell expansion and a decreased beta-cell fraction were predominantly observed in larger islets (islet area, >6415 micro m(2); P < 0.05) in control 1 and diabetic patients. The relative volume of beta-cell was found to be correlated with BMI in diabetic patients and normal organ donors. Moreover, decreased beta-cell but increased alpha-cell proportion in the islets suggests for a selective beta-cell loss in the pathogenesis of Korean type 2 diabetes.
Department of Endocrinology and Metabolism, Immunology, and Cell Biology Core Laboratory, Institutes of Medical Science, The Catholic University of Korea, Seoul, Korea 137-701. yoonk@catholic.ac.kr
Kun Ho
KH
Yoon
Seung Hyun
SH
Ko
Jae Hyoung
JH
Cho
Jung Min
JM
Lee
Yu Bae
YB
Ahn
Ki Ho
KH
Song
Soon Jib
SJ
Yoo
Moo Il
MI
Kang
Bong Yun
BY
Cha
Kwang Woo
KW
Lee
Ho Young
HY
Son
Sung Koo
SK
Kang
Hee Seung
HS
Kim
In Kyu
IK
Lee
Susan
S
Bonner-Weir
D000328:Adult; D000368:Aged; D015992:Body Mass Index; D048429:Cell Size; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D005260:Female; D006801:Humans; D007328:Insulin / Q000032:analysis; D007515:Islets of Langerhans / Q000473:pathology*; D007723:Korea; D008297:Male; D008875:Middle Aged; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000473:pathology; D014019:Tissue Donors
D007328:Insulin