Insulin treatment and high-fat diet feeding reduces the expression of three Tcf genes in rodent pancreas.
Specific single-nucleotide polymorphisms in intronic regions of human TCF7L2 are associated with an elevated risk of developing type 2 diabetes. Whether Tcf7l2 is expressed in pancreatic islets of rodent species at a considerable level, however, remains controversial. We used RT-PCR and quantitative RT-PCR to examine Tcf7l2 expression in rodent gut, pancreas, isolated pancreatic islets, and cultured cell lines. The expression level of Tcf7l2 was relatively lower in the pancreas compared to the gut or the pancreatic β-cell line Ins-1. Immunostaining did not detect a Tcf7l2 signal in mouse pancreatic islets. Endogenous canonical Wnt activity was not appreciable in the pancreas of TOPGAL transgenic mice. Both Tcf7 and Tcf7l1, but not Lef1, were expressed in the pancreas. The expression of the three Tcf genes (Tcf7, Tcf7l1, and Tcf7l2) in the pancreas was reduced by treatment with insulin or high-fat diet feeding, in contrast to the stimulation of Tcf7l2 expression by insulin in the gut. We suggest that hyperinsulinemia represses Tcf gene expression in the pancreas. Whether and how this reduction alters the function of pancreatic β cells during hyperinsulinemia deserves further investigation.
Columbus
Joshua
J
Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
Chiang
YuTing
Y
Shao
Weijuan
W
Zhang
Nina
N
Wang
Dingyan
D
Gaisano
Herbert Y
HY
Wang
Qinghua
Q
Irwin
David M
DM
Jin
Tianru
T
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology; D004041:Dietary Fats / Q000008:administration & dosage* / Q000633:toxicity; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D051538:Hepatocyte Nuclear Factor 1-alpha; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D051822:T Cell Transcription Factor 1 / Q000235:genetics; D051820:TCF Transcription Factors / Q000235:genetics* / Q000378:metabolism; D058125:Transcription Factor 7-Like 1 Protein; D058118:Transcription Factor 7-Like 2 Protein; D051153:Wnt Proteins / Q000378:metabolism
D017931:DNA Primers; D004041:Dietary Fats; D051538:Hepatocyte Nuclear Factor 1-alpha; C496488:Hnf1a protein, mouse; D007328:Insulin; D012333:RNA, Messenger; D051822:T Cell Transcription Factor 1; D051820:TCF Transcription Factors; C544912:TCF7L1 protein, human; C544894:TCF7L2 protein, human; C544913:Tcf7l1 protein, mouse; C544895:Tcf7l2 protein, mouse; D058125:Transcription Factor 7-Like 1 Protein; D058118:Transcription Factor 7-Like 2 Protein; D051153:Wnt Proteins