Effect of aging on insulin secretory function and expression of beta cell function-related genes of islets.
Recently, the glucose-stimulated insulin release of isolated human islets has been shown to deteriorate progressively with advancing donor age. This decline in beta cell function with aging may contribute to the increasing development of IGT and type 2 diabetes and also to the progressive nature of the disease. This study was to see whether there is any change in expression of beta cell function-related genes in islets with aging. Islets were isolated from young (2-month old) and old (22-24-month old) LETO rats and C57BL/6N mice. The in vitro GSIR index was significantly lower in islets from old mice compared with young mice. In real-time RT-PCR, PDX-1, insulin, GLUT2 and prohormone convertase 1/3 gene expression in islets was markedly lower in old rats (33%, 13%, 20% and 34%, respectively) and old mice (56%, 42%, 28% and 22%, respectively) compared with young animals. On the other hand, genes not specifically related to beta cell-specific function, such as caspase 3, superoxide dismutase 2 and glycerol kinase were not significantly different in expression in islets according to age. In conclusion, with increasing age, insulin secretory function of islets deteriorates accompanied with a decrease in expression of beta cell-specific genes including PDX-1.
Ihm
Sung-Hee
SH
Department of Internal Medicine, College of Medicine, Hallym University, Chunchon 200-702, Korea.
Moon
Hong Ju
HJ
Kang
Jun Goo
JG
Park
Cheol Young
CY
Oh
Ki Won
KW
Jeong
In Kyung
IK
Oh
Yang-Seok
YS
Park
Sung Woo
SW
D000375:Aging / Q000502:physiology*; D000818:Animals; D018507:Gene Expression Regulation, Developmental; D051273:Glucose Transporter Type 2 / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000502:physiology*; D007515:Islets of Langerhans / Q000254:growth & development / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D020318:Rats, Long-Evans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics
D051273:Glucose Transporter Type 2; D018398:Homeodomain Proteins; D007328:Insulin; D012333:RNA, Messenger; C495682:Slc2a2 protein, mouse; C495683:Slc2a2 protein, rat; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein