Improved Glucose Tolerance via Enhanced Glucose-Dependent Insulin Secretion in Dipeptidyl Peptidase IV-Deficient Fischer Rats

2001 ◽  
Vol 284 (2) ◽  
pp. 501-506 ◽  
Author(s):  
Tadashi Nagakura ◽  
Nobuyuki Yasuda ◽  
Kazuto Yamazaki ◽  
Hironori Ikuta ◽  
Seiji Yoshikawa ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Fischer Rats

scholarly journals Long-term inhibition of dipeptidyl peptidase IV improves glucose tolerance and preserves islet function in mice

2002 ◽  
pp. 717-727 ◽  
Author(s):  
MK Reimer ◽  
JJ Holst ◽  
B Ahren
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Dipeptidyl Peptidase ◽  
Normal Diet ◽  
Dipeptidyl Peptidase Iv ◽  
Islet Function ◽  
High Fat ◽  
Islet Size

OBJECTIVES: Inhibitors of the glucagon-like peptide-1 (GLP-1)-degrading enzyme, dipeptidyl peptidase IV (DPPIV), are being explored in the treatment of diabetes. We examined the long-term influence of a selective, orally active inhibitor of DPPIV (NVP DPP728), in normal female C57BL/6J mice and such mice rendered glucose-intolerant and insulin-resistant by feeding a high-fat diet. DESIGN: In mice fed a standard diet (11% fat) or a high-fat diet (58% fat), NVP DPP728 (0.12 micromol/g body weight) was administered in the drinking water for an 8 week period. RESULTS: DPPIV inhibition reduced plasma DPPIV activity to 0.01+/-0.03 mU/ml vs 3.26+/-0.19 mU/ml in controls (P<0.001). Glucose tolerance after gastric glucose gavage, as judged by the area under the curve for plasma glucose levels over the 120 min study period, was increased after 8 weeks by NVP DPP728 in mice fed normal diet (P=0.029) and in mice fed a high-fat diet (P=0.036). This was accompanied by increased plasma levels of insulin and intact GLP-1. Glucose-stimulated insulin secretion from islets isolated from NVP DPP728-treated animals after 8 weeks of treatment was increased as compared with islets from control animals at 5.6, 8.3 and 11.1 mmol/l glucose both in mice fed normal diet and in mice fed a high-fat diet (both P<0.05). Islet insulin and glucagon immunocytochemistry revealed that NVP DPP728 did not affect the islet architecture. However, the expression of immunoreactive glucose transporter isoform-2 (GLUT-2) was increased by DPPIV inhibition, and in mice fed a high-fat diet, islet size was reduced after treatment with NVP DPP728 from 16.7+/-2.6 x 10(3) microm(2) in controls to 7.6+/-1.0 x 10(3) microm(2) (P=0.0019). CONCLUSION: Long-term DPPIV inhibition improves glucose tolerance in both normal and glucose-intolerant mice through improved islet function as judged by increased GLUT-2 expression, increased insulin secretion and protection from increased islet size in insulin resistance.

scholarly journals Corrigendum to: Kinetic study of the processing by dipeptidyl-peptidase IV/CD26 of neuropeptides involved in pancreatic insulin secretion (FEBS 25376)

FEBS Letters ◽  
2002 ◽  
Vol 512 (1-3) ◽  
pp. 353-353
Author(s):  
Anne-Marie Lambeir ◽  
Christine Durinx ◽  
Paul Proost ◽  
Jo Van Damme ◽  
Simon Scharpé ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Kinetic Study ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Pancreatic Insulin

Effects of the dipeptidyl peptidase-IV inhibitor ASP8497 on glucose tolerance in animal models of secondary failure

2009 ◽  
Vol 622 (1-3) ◽  
pp. 71-77 ◽  
Author(s):  
Yuka Someya ◽  
Ryosuke Nakano ◽  
Atsuo Tahara ◽  
Toshiyuki Takasu ◽  
Asako Takeuchi ◽  
...  
Keyword(s):  
Animal Models ◽  
Glucose Tolerance ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Secondary Failure

scholarly journals Kinetic study of the processing by dipeptidyl-peptidase IV/CD26 of neuropeptides involved in pancreatic insulin secretion

FEBS Letters ◽  
2001 ◽  
Vol 507 (3) ◽  
pp. 327-330 ◽  
Author(s):  
Anne-Marie Lambeir ◽  
Christine Durinx ◽  
Paul Proost ◽  
Jo Van Damme ◽  
Simon Scharpé ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Kinetic Study ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Pancreatic Insulin
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