Bioactivity of a modified human Glucagon-like peptide-1

Xu, Fangfang; Wang, Kevin Yueju; Wang, Nan; Li, Gangqiang; Liu, Dehu

doi:10.1371/journal.pone.0171601

Cited by 4 publications

(4 citation statements)

References 35 publications

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“…The plasma glucose level in the control group of mice remained high for at least 400 min, and then began to decrease, possibly due to hunger (at 1000 min with a blood glucose level of 16.44 ± 2.58 mmol/L, comparable with 15.35 ± 1.82 mmol/L when fasted overnight in OGTT, as shown in Fig 5A ); while the blood glucose level in the test group decreased gradually over a period of 60–1,000 min ( Fig 5B ). These data demonstrated that the effect of 6×mGLP-1 occurring over an extended period of time suggested its ability to gradually lower plasma glucose, without the risk of hypoglycemia (5.87 ± 1.31 mmol/L glucose concentration at 1,000 min, nearly 16.7 hours, much longer than our previous monomer mGLP-1 [ 29 ]). A significant difference ( P = 0.026) between the two groups in blood glucose levels developed rapidly within 10 min and the separation lasted throughout the entire experiment.…”

Section: Resultssupporting

confidence: 52%

Modified human glucagon-like peptide-1 (GLP-1) produced in E. coli has a long-acting therapeutic effect in type 2 diabetic mice

Wang

et al. 2017

PLoS ONE

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Glucagon-like peptide 1 (GLP-1) is a very potent insulinotropic hormone secreted into the blood stream after eating. Thus, it has potential to be used in therapeutic treatment of diabetes. The half-life of GLP-1, however, is very short due to its rapid cleavage by dipeptidyl peptidase IV (DPP-IV). This presents a great challenge if it is to be used as a therapeutic drug. GLP-1, like many other small peptides, is commonly produced through chemical synthesis, but is limited by cost and product quantity. In order to overcome these problems, a sequence encoding a six codon-optimized tandem repeats of modified GLP-1 was constructed and expressed in the E. coli to produce a protease-resistant protein, 6×mGLP-1. The purified recombinant 6×mGLP-1, with a yield of approximately 20 mg/L, could be digested with trypsin to obtain single peptides. The single mGLP-1 peptides significantly stimulated the proliferation of a mouse pancreatic β cell line, MIN6. The recombinant peptide also greatly improved the oral glucose tolerance test of mice, exerted a positive glucoregulatory effect, and most notably had a glucose lowering effect for as long as 16.7 hours in mice altered to create a type 2 diabetic condition and exerted a positive glucoregulatory effect in db/db mice. These results indicate that recombinant 6×mGLP-1 has great potential to be used as an effective and cost-efficient drug for the treatment of type 2 diabetes.

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Section: Resultssupporting

confidence: 52%

Modified human glucagon-like peptide-1 (GLP-1) produced in E. coli has a long-acting therapeutic effect in type 2 diabetic mice

Wang

et al. 2017

PLoS ONE

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“…The enzymatic stability results were compared between the free Lira and Lira encapsulated in NPs. There was no Lira detected after the 2-h incubation of free Lira with SGF or SIF, which is due to the presence of amino acids, especially the aromatic ones, in the Lira structure, which makes it vulnerable to pepsin–pancreatin digestion [35]. The results revealed that PLGA NPs were effective in protecting 71% and 87% of Lira from pepsin and pancreatin digestion after a 2-h incubation with SGF and SIF, respectively.…”

Section: Discussionmentioning

confidence: 99%

Encapsulation in Polymeric Nanoparticles Enhances the Enzymatic Stability and the Permeability of the GLP-1 Analog, Liraglutide, Across a Culture Model of Intestinal Permeability

et al. 2019

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The potential of poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) to overcome the intestinal barrier that limits oral liraglutide delivery was evaluated. Liraglutide-loaded PLGA NPs were prepared by the double emulsion solvent evaporation method. In vitro release kinetics and enzymatic degradation studies were conducted, mimicking the gastrointestinal environment. The permeability of liraglutide solution, liraglutide-loaded PLGA NPs, and liraglutide in the presence of the absorption enhancer PN159 peptide was tested on the Caco-2 cell model. Liraglutide release from PLGA NPs showed a biphasic release pattern with a burst effect of less than 15%. The PLGA nanosystem protected the encapsulated liraglutide from the conditions simulating the gastric environment. The permeability of liraglutide encapsulated in PLGA NPs was 1.5-fold higher (24 × 10−6 cm/s) across Caco-2 cells as compared to liraglutide solution. PLGA NPs were as effective at elevating liraglutide penetration as the tight junction-opening PN159 peptide. No morphological changes were seen in the intercellular junctions of Caco-2 cells after treatment with liraglutide-PLGA NPs, confirming the lack of a paracellular component in the transport mechanism. PLGA NPs, by protecting liraglutide from enzyme degradation and enhancing its permeability across intestinal epithelium, hold great potential as carriers for oral GLP-1 analog delivery.

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“…GLP-1 has multiple beneficial effects on β cells, including an increase in their number by inhibiting apoptosis and enhancing neogenesis as well as promoting its proliferation. In a study carried out in 2016 by Xu et al [ 14 ], it was found that a chemically modified GLP-1 (mGLP-1) analog promotes the proliferation of pancreatic mouse β cells, upregulating the expression of cyclin E, CDK2, Bcl-2, Bax, and p21. The cyclin E-CDK2 complex plays an important role in the regulation of the G1 phase of the G1/S cell cycle, while p21 is a universal cyclin-dependent kinase (CKI) inhibitor.…”

Section: Discussionmentioning

confidence: 99%

“…The cyclin E-CDK2 complex plays an important role in the regulation of the G1 phase of the G1/S cell cycle, while p21 is a universal cyclin-dependent kinase (CKI) inhibitor. Meanwhile, the Bcl-2 and Bax genes, two important members of the Bcl-2 gene family, have opposite functions, inhibiting or promoting cell apoptosis, respectively[ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Insulinoma after sleeve gastrectomy: A case report

Lobaton-Ginsberg¹,

Sotelo-González²,

Ramírez‐Rentería³

et al. 2022

WJCC

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BACKGROUND Laparoscopic sleeve gastrectomy (LSG) has been proposed as an effective and durable treatment for severe obesity and glucose metabolism disorders, and its prevalence has increased from 5% to 37% since 2008. One common complication after bariatric surgery is a postprandial hyperinsulinemic hypoglycemic state. While rare, insulinomas can cause this state, where symptoms are more common in the fasting state; thus, evaluation of insulin secretion is needed. Until now, there have been no reports of insulinoma after LSG. CASE SUMMARY We describe the case of a 43-year-old woman who was referred to the obesity clinic 2 years after LSG was performed. She had symptoms of hypoglycemia predominantly in the fasting state and documented hypoglycemia of less than 30 mg/dL, which are compatible with Whipple’s triad. Initially, dumping syndrome was suspected, but after a second low fasting plasma glucose was documented, a 72-h fasting test was performed that tested positive. Computed tomography and endoscopic ultrasound were performed, identifying the presence of a homogeneous hypoechoic semioval tumoral lesion in the pancreas. The diagnosis was compatible with insulinoma. After laparoscopic enucleation of the insulinoma, the symptoms and hypoglycemia disappeared. The histopathological report described a well-differentiated grade 2 neuroendocrine tumor with positive chromogranin and synaptophysin and Ki67 immunopositivity in 4% of the neoplastic cells. CONCLUSION Insulinoma after LSG is a rare condition, and clinicians must be aware of it, especially if the patient has hypoglycemic symptoms during the fasting state.

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Bioactivity of a modified human Glucagon-like peptide-1

Cited by 4 publications

References 35 publications

Modified human glucagon-like peptide-1 (GLP-1) produced in E. coli has a long-acting therapeutic effect in type 2 diabetic mice

Modified human glucagon-like peptide-1 (GLP-1) produced in E. coli has a long-acting therapeutic effect in type 2 diabetic mice

Encapsulation in Polymeric Nanoparticles Enhances the Enzymatic Stability and the Permeability of the GLP-1 Analog, Liraglutide, Across a Culture Model of Intestinal Permeability

Insulinoma after sleeve gastrectomy: A case report

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