Up-regulated pancreatic tissue microRNA-375 associates with human type 2 diabetes through beta-cell deficit and islet amyloid deposition.
OBJECTIVE
The aim of this study was to examine correlations of the islet-specific microRNA-375 expression to islet amyloid formation and pancreatic islet damage in human type 2 diabetes.


METHODS
Autopsy pancreas samples from 40 type 2 diabetic and 15 nondiabetic patients were used to detect microRNA-375 expression using real-time quantitative polymerase chain reaction. Serial paraffin sections of the corresponding type 2 diabetic and nondiabetic cases were stained by immunofluorescence to evaluate for amylin expression, amyloid formation, and proportions of alpha and beta cells.


RESULTS
Pancreatic microRNA-375 expression was increased in type 2 diabetic patients comparing with the nondiabetic patients (median, 4.02 for the diabetic patients vs 0.92 for the nondiabetic patients; P = 0.0001). The median was 6.14 for the diabetic patients with islet amyloid and 3.51 for islet amyloid-free diabetic patients. The expression level of microRNA-375 correlated positively with the frequency and the severity of islet amyloid formation and negatively with proportions of islet beta-cells and amylin-positive area, and islet mitochondria density.


CONCLUSIONS
Up-regulated microRNA-375 is associated with type 2 diabetes and pancreatic islet amyloid formation and beta-cell deficit. microRNA-375 may serve as a biomarker for known and novel pathways in the pathogenesis of type 2 diabetes related to islet amyloid deposition and beta-cell dysfunction.
Zhao
Hailu
H
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, People's Republic of China.
Guan
Jing
J
Lee
Heung-Man
HM
Sui
Yi
Y
He
Lan
L
Siu
Jennifer J
JJ
Tse
Patty P P
PP
Tong
Peter C Y
PC
Lai
Fernand M M
FM
Chan
Juliana C N
JC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000682:Amyloid / Q000378:metabolism; D001344:Autopsy; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D058228:Islet Amyloid Polypeptide / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D000682:Amyloid; D058228:Islet Amyloid Polypeptide; C540933:MIRN375 microRNA, human; D035683:MicroRNAs