| Title |
Lixisenatide accelerates restoration of normoglycemia and improves human beta-cell function and survival in diabetic immunodeficient NOD–scid IL-2rgnull RIP-DTR mice engrafted with human islets
|
|---|---|
| Published in |
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, August 2015
|
| DOI | 10.2147/dmso.s87253 |
| Pubmed ID | |
| Authors |
Chaoxing Yang, Matthias Loehn, Agata Jurczyk, Natalia Przewozniak, Linda Leehy, Pedro L Herrera, Leonard D Shultz, Dale L Greiner, David M Harlan, Rita Bortell |
| Abstract |
Glucagon-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. Five 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. Diabetic 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. Diabetic 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. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| India | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 22 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 22 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 6 | 27% |
| Professor | 4 | 18% |
| Student > Ph. D. Student | 3 | 14% |
| Student > Doctoral Student | 2 | 9% |
| Student > Master | 1 | 5% |
| Other | 1 | 5% |
| Unknown | 5 | 23% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 7 | 32% |
| Biochemistry, Genetics and Molecular Biology | 6 | 27% |
| Psychology | 2 | 9% |
| Computer Science | 1 | 5% |
| Agricultural and Biological Sciences | 1 | 5% |
| Other | 1 | 5% |
| Unknown | 4 | 18% |
Attention Score in Context
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 July 2020.
All research outputs
#7,994,598
of 25,460,914 outputs
Outputs from Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
#324
of 1,184 outputs
Outputs of similar age
#86,355
of 276,614 outputs
Outputs of similar age from Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
#6
of 17 outputs
Altmetric has tracked 25,460,914 research outputs across all sources so far. This one has received more attention than most of these and is in the 67th percentile.
So far Altmetric has tracked 1,184 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.5. This one has gotten more attention than average, scoring higher than 71% of its peers.
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We're also able to compare this research output to 17 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 64% of its contemporaries.