scholarly journals Generation of Dipeptidyl Peptidase-IV-Inhibiting Peptides fromβ-Lactoglobulin Secreted byLactococcus lactis

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Suguru Shigemori ◽  
Kazushi Oshiro ◽  
Pengfei Wang ◽  
Yoshinari Yamamoto ◽  
Yeqin Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Expression System ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Delivery Vehicle ◽  
Dpp Iv

Previous studies showed that hydrolysates ofβ-lactoglobulin (BLG) prepared using gastrointestinal proteases strongly inhibit dipeptidyl peptidase-IV (DPP-IV) activityin vitro. In this study, we developed a BLG-secretingLactococcus lactisstrain as a delivery vehicle andin situexpression system. Interestingly, trypsin-digested recombinant BLG fromL. lactisinhibited DPP-IV activity, suggesting that BLG-secretingL. lactismay be useful in the treatment of type 2 diabetes mellitus.

scholarly journals A Novel Dipeptidyl Peptidase IV Inhibitory Tea Peptide Improves Pancreatic β-Cell Function and Reduces α-Cell Proliferation in Streptozotocin-Induced Diabetic Mice

2019 ◽  
Vol 20 (2) ◽  
pp. 322 ◽  
Author(s):  
Yating Lu ◽  
Peng Lu ◽  
Yu Wang ◽  
Xiaodong Fang ◽  
Jianming Wu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Type 2 Diabetes ◽  
Inhibitory Activity ◽  
Black Tea ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Inhibitory Peptides ◽  
Dpp Iv

Dipeptidyl peptidase IV (DPP-IV) inhibitors occupy a growing place in the drugs used for the management of type 2 diabetes. Recently, food components, including food-derived bioactive peptides, have been suggested as sources of DPP-IV inhibitors without side effects. Chinese black tea is a traditional health beverage, and it was used for finding DPP-IV inhibitory peptides in this study. The ultra-filtrated fractions isolated from the aqueous extracts of black tea revealed DPP-IV inhibitory activity in vitro. Four peptides under 1 kDa were identified by SDS-PAGE and LC-MS/MS (Liquid Chromatography-Mass Spectrometry-Mass Spectrometry) from the ultra-filtrate. The peptide II (sequence: AGFAGDDAPR), with a molecular mass of 976 Da, showed the greatest DPP-IV inhibitory activity (in vitro) among the four peptides. After administration of peptide II (400 mg/day) for 57 days to streptozotocin (STZ)-induced hyperglycemic mice, the concentration of glucagon-like peptide-1 (GLP-1) in the blood increased from 9.85 ± 1.96 pmol/L to 19.22 ± 6.79 pmol/L, and the insulin level was increased 4.3-fold compared to that in STZ control mice. Immunohistochemistry revealed the improved function of pancreatic beta-cells and suppressed proliferation of pancreatic alpha-cells. This study provides new insight into the use of black tea as a potential resource of food-derived DPP-IV inhibitory peptides for the management of type 2 diabetes.

scholarly journals N-terminal His(7)-modification of glucagon-like peptide-1(7-36) amide generates dipeptidyl peptidase IV-stable analogues with potent antihyperglycaemic activity

2004 ◽  
Vol 180 (3) ◽  
pp. 379-388 ◽  
Author(s):  
BD Green ◽  
MH Mooney ◽  
VA Gault ◽  
N Irwin ◽  
CJ Bailey ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Plasma Glucose ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Dpp Iv ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1(7-36)amide (GLP-1) possesses several unique and beneficial effects for the potential treatment of type 2 diabetes. However, the rapid inactivation of GLP-1 by dipeptidyl peptidase IV (DPP IV) results in a short half-life in vivo (less than 2 min) hindering therapeutic development. In the present study, a novel His(7)-modified analogue of GLP-1, N-pyroglutamyl-GLP-1, as well as N-acetyl-GLP-1 were synthesised and tested for DPP IV stability and biological activity. Incubation of GLP-1 with either DPP IV or human plasma resulted in rapid degradation of native GLP-1 to GLP-1(9-36)amide, while N-acetyl-GLP-1 and N-pyroglutamyl-GLP-1 were completely resistant to degradation. N-acetyl-GLP-1 and N-pyroglutamyl-GLP-1 bound to the GLP-1 receptor but had reduced affinities (IC(50) values 32.9 and 6.7 nM, respectively) compared with native GLP-1 (IC(50) 0.37 nM). Similarly, both analogues stimulated cAMP production with EC(50) values of 16.3 and 27 nM respectively compared with GLP-1 (EC(50) 4.7 nM). However, N-acetyl-GLP-1 and N-pyroglutamyl-GLP-1 exhibited potent insulinotropic activity in vitro at 5.6 mM glucose (P<0.05 to P<0.001) similar to native GLP-1. Both analogues (25 nM/kg body weight) lowered plasma glucose and increased plasma insulin levels when administered in conjunction with glucose (18 nM/kg body weight) to adult obese diabetic (ob/ob) mice. N-pyroglutamyl-GLP-1 was substantially better at lowering plasma glucose compared with the native peptide, while N-acetyl-GLP-1 was significantly more potent at stimulating insulin secretion. These studies indicate that N-terminal modification of GLP-1 results in DPP IV-resistant and biologically potent forms of GLP-1. The particularly powerful antihyperglycaemic action of N-pyroglutamyl-GLP-1 shows potential for the treatment of type 2 diabetes.

Association between HbA1c and dipeptidyl peptidase IV activity in type 2 diabetes mellitus

2012 ◽  
Vol 413 (11-12) ◽  
pp. 1020-1021 ◽  
Author(s):  
Luziane Potrich Bellé ◽  
Paula Eliete Rodrigues Bitencourt ◽  
Karine Santos De Bona ◽  
Rafael Noal Moresco ◽  
Maria Beatriz Moretto
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv

scholarly journals Novel dipeptidyl peptidase IV resistant analogues of glucagon-like peptide-1(7-36)amide have preserved biological activities in vitro conferring improved glucose-lowering action in vivo

2003 ◽  
Vol 31 (3) ◽  
pp. 529-540 ◽  
Author(s):  
BD Green ◽  
VA Gault ◽  
MH Mooney ◽  
N Irwin ◽  
CJ Bailey ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Biological Activities ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Glucose Lowering ◽  
Dpp Iv ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Although the incretin hormone glucagon-like peptide-1 (GLP-1) is a potent stimulator of insulin release, its rapid degradation in vivo by the enzyme dipeptidyl peptidase IV (DPP IV) greatly limits its potential for treatment of type 2 diabetes. Here, we report two novel Ala(8)-substituted analogues of GLP-1, (Abu(8))GLP-1 and (Val(8))GLP-1 which were completely resistant to inactivation by DPP IV or human plasma. (Abu(8))GLP-1 and (Val(8))GLP-1 exhibited moderate affinities (IC(50): 4.76 and 81.1 nM, respectively) for the human GLP-1 receptor compared with native GLP-1 (IC(50): 0.37 nM). (Abu(8))GLP-1 and (Val(8))GLP-1 dose-dependently stimulated cAMP in insulin-secreting BRIN BD11 cells with reduced potency compared with native GLP-1 (1.5- and 3.5-fold, respectively). Consistent with other mechanisms of action, the analogues showed similar, or in the case of (Val(8))GLP-1 slightly impaired insulin releasing activity in BRIN BD11 cells. Using adult obese (ob/ob) mice, (Abu(8))GLP-1 had similar glucose-lowering potency to native GLP-1 whereas the action of (Val(8))GLP-1 was enhanced by 37%. The in vivo insulin-releasing activities were similar. These data indicate that substitution of Ala(8) in GLP-1 with Abu or Val confers resistance to DPP IV inactivation and that (Val(8))GLP-1 is a particularly potent N-terminally modified GLP-1 analogue of possible use in type 2 diabetes.

Comparison of the Effects of Mitiglinide and Glibenclamide Administered in Combination with the Dipeptidyl Peptidase-IV Inhibitor Sitagliptin in Rats with Streptozotocin-Nicotinamide-Induced Type 2 Diabetes

Drug Research ◽  
2017 ◽  
Vol 67 (07) ◽  
pp. 396-403 ◽  
Author(s):  
Kenji Akahane ◽  
Kazuma Ojima ◽  
Ayaka Yokoyama ◽  
Toshihiro Inoue ◽  
Sumiyoshi Kiguchi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Oral Glucose ◽  
Diabetic Patients ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Dpp Iv

Abstract We compared the individual effects of mitiglinide and glibenclamide administered in combination with the dipeptidyl peptidase-IV (DPP-IV) inhibitor sitagliptin on plasma DPP-IV activity and blood glucose levels in rats with streptozotocin-nicotinamide-induced type 2 diabetes (STZ-NA rats). We examined the inhibitory activity of mitiglinide and glibenclamide as well as their combination with sitagliptin on plasma DPP-IV activity in STZ-NA rats. The oral glucose tolerance test (OGTT) was used to compare effects of mitiglinide, glibenclamide, and their combination with sitagliptin on blood glucose levels in STZ-NA rats. Mitiglinide and glibenclamide did not inhibit rat DPP-IV and did not influence the inhibitory effect of sitagliptin on rat plasma DPP-IV activity. In STZ-NA rats, plasma glucose levels were stronger suppressed by a combination of mitiglinide and sitagliptin than by either drug used alone. However, no clear effect of the combination of glibenclamide and sitagliptin was observed. These results indicate that the combination of mitiglinide and sitagliptin has a lower risk of hypoglycemia in the rats with induced type 2 diabetes compared with the combination of glibenclamide and sitagliptin. The combination of mitiglinide and sitagliptin can be a promising combination for the treatment of diabetic patients.

Emerging Drug Candidates of Dipeptidyl Peptidase IV (DPP IV) Inhibitor Class for the Treatment of Type 2 Diabetes

2009 ◽  
Vol 10 (1) ◽  
pp. 71-87 ◽  
Author(s):  
Rajesh Gupta ◽  
Sameer Walunj ◽  
Ranjeet Tokala ◽  
Kishore Parsa ◽  
Santosh Singh ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Drug Candidates ◽  
Dpp Iv
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