Regulation of oligopeptide transporter (Pept-1) in experimental diabetes.
The knowledge of expression and biology of the intestinal oligopeptide transporter (Pept-1) in a metabolic disorder such as diabetes may have nutritional and pharmacological implications. To study this problem, rats were made diabetic by streptozotocin injection, and Western and Northern blot analyses and nuclear run-on assay were used to determine the protein and gene expressions of Pept-1 and its rate of transcription, respectively. Uncontrolled diabetes for 96 h increased the activity of Pept-1 in the brush-border membrane of intestinal mucosa. Studies of Michaelis-Menten constant, maximal velocity, and protein expression of Pept-1 indicated that an increase in the abundance of this transporter was responsible for the increased activity. Studies of the gene expression showed that uncontrolled diabetes increased the abundance of mRNA encoding Pept-1 without altering its rate of transcription. Lastly, studies of the specificity of the above effect showed that uncontrolled diabetes similarly affected the protein and gene expressions of Pept-1 located in the kidney. In conclusion, the data show that 1) uncontrolled diabetes has a tropic effect on Pept-1 and 2) the effect is systemic, and its molecular mechanism appears to be an increase in the stabilization of mRNA encoding Pept-1.
Gangopadhyay
Archana
A
Clinical Nutrition Research Unit, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Thamotharan
Manikkavasagar
M
Adibi
Siamak A
SA
D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004151:Dipeptides / Q000493:pharmacokinetics; D007421:Intestine, Small / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D008871:Microvilli / Q000378:metabolism; D000074011:Peptide Transporter 1; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D027981:Symporters
D002352:Carrier Proteins; D004151:Dipeptides; D000074011:Peptide Transporter 1; D012333:RNA, Messenger; C489940:Slc15a1 protein, rat; D027981:Symporters