Bioactive Peptides from Sodium Caseinate Hydrolysate with High Oral Absorption Regulate Blood Glucose in Type 2 Diabetic Mice via Inhibition of DPP-IV and Stimulation of GLP-1

Type 2 diabetes mellitus remains a critical global health challenge, driving the pursuit of novel therapeutic strategies. This study investigated the anti-diabetic efficacy of the peptide 1CBR, derived from sodium caseinate hydrolysate, administered orally at 25 mg/kg/day to db/db mice over a 4-week...

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Main Authors: Pei-Yu Wu, Cheng-Hong Hsieh, Ali Iqbal, Yu-Shun Lin, Ming-Wei Cheng, Ling-Hsuan Chang, Shang-Ming Huang, Kuo-Chiang Hsu
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Foods
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Online Access:https://www.mdpi.com/2304-8158/14/11/1953
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author Pei-Yu Wu
Cheng-Hong Hsieh
Ali Iqbal
Yu-Shun Lin
Ming-Wei Cheng
Ling-Hsuan Chang
Shang-Ming Huang
Kuo-Chiang Hsu
author_facet Pei-Yu Wu
Cheng-Hong Hsieh
Ali Iqbal
Yu-Shun Lin
Ming-Wei Cheng
Ling-Hsuan Chang
Shang-Ming Huang
Kuo-Chiang Hsu
author_sort Pei-Yu Wu
collection DOAJ
description Type 2 diabetes mellitus remains a critical global health challenge, driving the pursuit of novel therapeutic strategies. This study investigated the anti-diabetic efficacy of the peptide 1CBR, derived from sodium caseinate hydrolysate, administered orally at 25 mg/kg/day to db/db mice over a 4-week period. Glucose tolerance was evaluated via oral glucose tolerance tests (OGTT), while plasma dipeptidyl peptidase-IV (DPP-IV) activity, glucagon-like peptide-1 (GLP-1), and insulin concentrations were quantified using enzyme-linked immunosorbent assays (ELISA). Two bioactive peptides, GPFPLPD and APDSGNFR, were isolated and characterized, exhibiting half-maximal inhibitory concentrations (IC<sub>50</sub>) of 99.12 µM and 73.07 µM for DPP-IV inhibition, respectively, and both significantly stimulated GLP-1 secretion in enteroendocrine cells in vitro. Pharmacokinetic analysis in Sprague–Dawley rats demonstrated oral bioavailability of 11.28% and 19.12% for these peptides, surpassing typical expectations for peptide-based agents. Collectively, these results provide compelling evidence that 1CBR-derived peptides exert glucose-lowering effects through the dual mechanisms of DPP-IV inhibition and GLP-1 stimulation, combined with favorable oral absorption profiles. These findings underscore the potential of 1CBR peptides as promising candidates for development into nutraceuticals or pharmaceutical agents for diabetes management.
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spelling doaj-art-2203e56c7aa340288d8ec823f46d82d32025-08-20T02:23:07ZengMDPI AGFoods2304-81582025-05-011411195310.3390/foods14111953Bioactive Peptides from Sodium Caseinate Hydrolysate with High Oral Absorption Regulate Blood Glucose in Type 2 Diabetic Mice via Inhibition of DPP-IV and Stimulation of GLP-1Pei-Yu Wu0Cheng-Hong Hsieh1Ali Iqbal2Yu-Shun Lin3Ming-Wei Cheng4Ling-Hsuan Chang5Shang-Ming Huang6Kuo-Chiang Hsu7Department of Nutrition, China Medical University, 100 Sec. 1, Jingmao Road, Taichung 406040, TaiwanDepartment of Nutrition, China Medical University, 100 Sec. 1, Jingmao Road, Taichung 406040, TaiwanDepartment of Nutrition, China Medical University, 100 Sec. 1, Jingmao Road, Taichung 406040, TaiwanDepartment of Nutrition, China Medical University, 100 Sec. 1, Jingmao Road, Taichung 406040, TaiwanDepartment of Nutrition, China Medical University, 100 Sec. 1, Jingmao Road, Taichung 406040, TaiwanDepartment of Nutrition, China Medical University, 100 Sec. 1, Jingmao Road, Taichung 406040, TaiwanDepartment of Nutrition, China Medical University, 100 Sec. 1, Jingmao Road, Taichung 406040, TaiwanDepartment of Nutrition, China Medical University, 100 Sec. 1, Jingmao Road, Taichung 406040, TaiwanType 2 diabetes mellitus remains a critical global health challenge, driving the pursuit of novel therapeutic strategies. This study investigated the anti-diabetic efficacy of the peptide 1CBR, derived from sodium caseinate hydrolysate, administered orally at 25 mg/kg/day to db/db mice over a 4-week period. Glucose tolerance was evaluated via oral glucose tolerance tests (OGTT), while plasma dipeptidyl peptidase-IV (DPP-IV) activity, glucagon-like peptide-1 (GLP-1), and insulin concentrations were quantified using enzyme-linked immunosorbent assays (ELISA). Two bioactive peptides, GPFPLPD and APDSGNFR, were isolated and characterized, exhibiting half-maximal inhibitory concentrations (IC<sub>50</sub>) of 99.12 µM and 73.07 µM for DPP-IV inhibition, respectively, and both significantly stimulated GLP-1 secretion in enteroendocrine cells in vitro. Pharmacokinetic analysis in Sprague–Dawley rats demonstrated oral bioavailability of 11.28% and 19.12% for these peptides, surpassing typical expectations for peptide-based agents. Collectively, these results provide compelling evidence that 1CBR-derived peptides exert glucose-lowering effects through the dual mechanisms of DPP-IV inhibition and GLP-1 stimulation, combined with favorable oral absorption profiles. These findings underscore the potential of 1CBR peptides as promising candidates for development into nutraceuticals or pharmaceutical agents for diabetes management.https://www.mdpi.com/2304-8158/14/11/1953type 2 diabetes mellitussodium caseinate hydrolysatedipeptidyl peptidase-IVglucagon-like peptide-1
spellingShingle Pei-Yu Wu
Cheng-Hong Hsieh
Ali Iqbal
Yu-Shun Lin
Ming-Wei Cheng
Ling-Hsuan Chang
Shang-Ming Huang
Kuo-Chiang Hsu
Bioactive Peptides from Sodium Caseinate Hydrolysate with High Oral Absorption Regulate Blood Glucose in Type 2 Diabetic Mice via Inhibition of DPP-IV and Stimulation of GLP-1
Foods
type 2 diabetes mellitus
sodium caseinate hydrolysate
dipeptidyl peptidase-IV
glucagon-like peptide-1
title Bioactive Peptides from Sodium Caseinate Hydrolysate with High Oral Absorption Regulate Blood Glucose in Type 2 Diabetic Mice via Inhibition of DPP-IV and Stimulation of GLP-1
title_full Bioactive Peptides from Sodium Caseinate Hydrolysate with High Oral Absorption Regulate Blood Glucose in Type 2 Diabetic Mice via Inhibition of DPP-IV and Stimulation of GLP-1
title_fullStr Bioactive Peptides from Sodium Caseinate Hydrolysate with High Oral Absorption Regulate Blood Glucose in Type 2 Diabetic Mice via Inhibition of DPP-IV and Stimulation of GLP-1
title_full_unstemmed Bioactive Peptides from Sodium Caseinate Hydrolysate with High Oral Absorption Regulate Blood Glucose in Type 2 Diabetic Mice via Inhibition of DPP-IV and Stimulation of GLP-1
title_short Bioactive Peptides from Sodium Caseinate Hydrolysate with High Oral Absorption Regulate Blood Glucose in Type 2 Diabetic Mice via Inhibition of DPP-IV and Stimulation of GLP-1
title_sort bioactive peptides from sodium caseinate hydrolysate with high oral absorption regulate blood glucose in type 2 diabetic mice via inhibition of dpp iv and stimulation of glp 1
topic type 2 diabetes mellitus
sodium caseinate hydrolysate
dipeptidyl peptidase-IV
glucagon-like peptide-1
url https://www.mdpi.com/2304-8158/14/11/1953
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