GLUCOSE REGULATION OF DIPEPTIDYL PEPTIDASE IV GENE EXPRESSION IS MEDIATED BY HEPATOCYTE NUCLEAR FACTOR-1α IN EPITHELIAL INTESTINAL CELLS

• Published in: Clinical and experimental pharmacology & physiology 2008-12, Vol.35 (12), p.1433-1439
• Main Authors: Gu, Ning, Tsuda, Mariko, Matsunaga, Tetsuro, Adachi, Tetsuya, Yasuda, Koichiro, Ishihara, Akihiko, Tsuda, Kinsuke
• Format: Article
• Language: English
• Subjects: Caco-2; dipeptidyl peptidase IV; glucose regulation; hepatocyte nuclear factor-1α
• ISSN: 0305-1870; 1440-1681
• DOI: 10.1111/j.1440-1681.2008.05015.x

SUMMARY 1 Dipeptidyl peptidase IV (DPP‐IV) is a new drug target in the treatment of Type 2 diabetes. Dipeptidyl peptidase IV enzyme activity is significantly altered in Type 2 diabetic patients with hyperglycaemia, but the underlying molecular mechanisms remain unclear. 2 The first aim of the present study was to clarify whether glucose regulates DPP‐IV enzyme activity. To address this, DPP‐IV gene expression and enzyme activity were measured in Caco2 cells cultured in the presence of low (2.5 mmol/L) or high (16.7 mmol/L) concentrations of glucose. We observed that high glucose inhibited DPP‐IV gene expression and enzyme activity. 3 The second aim of the present study was to investigate whether hepatocyte nuclear factor (HNF)‐1α contributes to glucose regulation of DPP‐IV gene expression. To explore this question, associations between the gene expression of DPP‐IV and HNF‐1α were examined in Caco‐2 cells cultured in the presence of low (2.5 mmol/L) or high (16.7 mmol/L) glucose. We found that the pattern of glucose‐regulated DPP‐IV gene expression is similar to that of HNF‐1α. Moreover, to elucidate whether glucose regulation of DPP‐IV gene expression is affected when HNF‐1α is inhibited, we produced two stable cell lines in which a dominant‐negative mutant HNF‐1αR271G or basic vectors were stably expressed. We found that glucose regulation of DPP‐IV gene expression was compromised in HNF‐1αR271G cells, but was well maintained in basic vector cells. 4 These results suggest that glucose regulation of DPP‐IV gene expression is mediated by HNF‐1α.