ArticleDiabetes, metabolic syndrome and obesity : targets and therapy2013
Improved function and proliferation of adult human beta cells engrafted in diabetic immunodeficient NOD-scid IL2rγ(null) mice treated with alogliptin.
Article in Diabetes, metabolic syndrome and obesity : targets and therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 18 citations in OpenAlex.
- The pharmacokinetics and pharmacodynamics of alogliptin in children, adolescents, and adults with type 2 diabetes mellitus.European journal of clinical pharmacology · 2017Trial
- Exploring dose-response variability and relative severity assessment in STZ-induced diabetes male NSG mice.Scientific reports · 2024Article
- A human antibody against pathologic IAPP aggregates protects beta cells in type 2 diabetes models.Nature communications · 2023Article
- Recovery of viable endocrine-specific cells and transcriptomes from human pancreatic islet-engrafted mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Development of a liver-specific Tet-off AAV8 vector for improved safety of insulin gene therapy for diabetes.The journal of gene medicine · 2019Article
- Article
- Strategies for Diabetes Management: Using Newer Oral Combination Therapies Early in the Disease.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2016Review
- Application of pharmacometric approaches to evaluate effect of weight and renal function on pharmacokinetics of alogliptin.British journal of clinical pharmacology · 2016Article
- Potential for combination of dipeptidyl peptidase-4 inhibitors and sodium-glucose co-transporter-2 inhibitors for the treatment of type 2 diabetes.Diabetes, obesity & metabolism · 2015Review
- Review
- Viral infection of engrafted human islets leads to diabetes.Diabetes · 2015Article
- Alogliptin benzoate for management of type 2 diabetes.Vascular health and risk management · 2015Review
- Type 1 Diabetes Prevention in NOD Mice by Targeting DPPIV/CD26 Is Associated with Changes in CD8⁺T Effector Memory Subset.PloS one · 2015Article
- Lixisenatide accelerates restoration of normoglycemia and improves human beta-cell function and survival in diabetic immunodeficient NOD-scid IL-2rg(null) RIP-DTR mice engrafted with human islets.Diabetes, metabolic syndrome and obesity : targets and therapy · 2015Article
- Human β-cell regeneration: progress, hurdles, and controversy.Current opinion in endocrinology, diabetes, and obesity · 2014Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeDipeptidyl-peptidase-4 (DPP-4) inhibitors are known to increase insulin secretion and beta cell proliferation in rodents. To investigate the effects on human beta cells in vivo, we utilize immunodeficient mice transplanted with human islets. The study goal was to determine the efficacy of alogliptin, a DPP-4 inhibitor, to enhance human beta cell function and proliferation in an in vivo context using diabetic immunodeficient mice engrafted with human pancreatic islets.
methodsStreptozotocin-induced diabetic NOD-scid IL2rγ(null) (NSG) mice were transplanted with adult human islets in three separate trials. Transplanted mice were treated daily by gavage with alogliptin (30 mg/kg/day) or vehicle control. Islet graft function was compared using glucose tolerance tests and non-fasting plasma levels of human insulin and C-peptide; beta cell proliferation was determined by bromodeoxyuridine (BrdU) incorporation.
resultsGlucose tolerance tests were significantly improved by alogliptin treatment for mice transplanted with islets from two of the three human islet donors. Islet-engrafted mice treated with alogliptin also had significantly higher plasma levels of human insulin and C-peptide compared to vehicle controls. The percentage of insulin+BrdU+ cells in human islet grafts from alogliptin-treated mice was approximately 10-fold more than from vehicle control mice, consistent with a significant increase in human beta cell proliferation.
conclusionHuman islet-engrafted immunodeficient mice treated with alogliptin show improved human insulin secretion and beta cell proliferation compared to control mice engrafted with the same donor islets. Immunodeficient mice transplanted with human islets provide a useful model to interrogate potential therapies to improve human islet function and survival in vivo.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.