ArticleDiabetes, metabolic syndrome and obesity : targets and therapy2015
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.
Article in Diabetes, metabolic syndrome and obesity : targets and therapy, 2015. 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, 11 citations in OpenAlex.
- Diabetes-associated MYT1 and ST18 genes regulate human beta cell insulin secretion and survival via other diabetes risk genes.Diabetologia · 2026Article
- Allogeneic islet products for type 1 diabetes: Navigating nonclinical and manufacturing regulatory expectations.Stem cell reports · 2026Review
- Metabolic Stress Levels Influence the Ability of Myelin Transcription Factors to Regulate β-Cell Identity and Survival.Diabetes · 2024Article
- β-cell neogenesis: A rising star to rescue diabetes mellitus.Journal of advanced research · 2024Review
- The age-dependent regulation of pancreatic islet landscape is fueled by a HNF1a-immune signaling loop.Mechanisms of ageing and development · 2024Article
- A human antibody against pathologic IAPP aggregates protects beta cells in type 2 diabetes models.Nature communications · 2023Article
- A Method for Encapsulation and Transplantation into Diabetic Mice of Human Induced Pluripotent Stem Cells (hiPSC)-Derived Pancreatic Progenitors.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Preclinical Models to Evaluate the Human Response to Autoantigen and Antigen-Specific Immunotherapy in Human Type 1 Diabetes.Frontiers in endocrinology · 2022Review
- Human Beta Cell Regenerative Drug Therapy for Diabetes: Past Achievements and Future Challenges.Frontiers in endocrinology · 2021Review
- In vivo hyperglycaemia exposure elicits distinct period-dependent effects on human pancreatic progenitor differentiation, conveyed by oxidative stress.Acta physiologica (Oxford, England) · 2020Article
- 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
- Article
- Lack of acute xenogeneic graft- versus-host disease, but retention of T-cell function following engraftment of human peripheral blood mononuclear cells in NSG mice deficient in MHC class I and II expression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Age-dependent human β cell proliferation induced by glucagon-like peptide 1 and calcineurin signaling.The Journal of clinical investigation · 2017Article
- An Update on the Effect of Incretin-Based Therapies on β-Cell Function and Mass.Diabetes & metabolism journal · 2016Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveGlucagon-like peptide-1 induces glucose-dependent insulin secretion and, in rodents, increases proliferation and survival of pancreatic beta cells. To investigate the effects on human beta cells, we used immunodeficient mice transplanted with human islets. The goal was to determine whether lixisenatide, a glucagon-like peptide-1 receptor agonist, improves human islet function and survival in vivo.
methodsFive independent transplant studies were conducted with human islets from five individual donors. Diabetic human islet-engrafted immunodeficient mice were treated with lixisenatide (50, 150, and 500 µg/kg) or vehicle. Islet function was determined by blood glucose, plasma human insulin/C-peptide, and glucose tolerance tests. Grafts were analyzed for total beta- and alpha-cell number, percent proliferation, and levels of apoptosis.
resultsDiabetic mice transplanted with marginal human islet mass and treated with lixisenatide were restored to euglycemia more rapidly than vehicle-treated mice. Glucose tolerance tests, human plasma insulin, and glucose-stimulation indices of lixisenatide-treated mice were significantly improved compared to vehicle-treated mice. The percentages of proliferating or apoptotic beta cells at graft recovery were not different between lixisenatide-treated and vehicle-treated mice. Nevertheless, in one experiment we found a significant twofold to threefold increase in human beta-cell numbers in lixisenatide-treated compared to vehicle-treated mice.
conclusionDiabetic human islet-engrafted immunodeficient mice treated with lixisenatide show improved restoration of normoglycemia, human plasma insulin, and glucose tolerance compared to vehicle-treated mice engrafted with the same donor islets. Because the proliferative capacity of human beta cells is limited, improved beta-cell survival coupled with enhanced beta-cell function following lixisenatide treatment may provide the greatest benefit for diabetic patients with reduced functional islet mass.
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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.