A static glucose-stimulated insulin secretion (sGSIS) assay that is significantly predictive of time to diabetes reversal in the human islet bioassay
Introduction Static incubation (static glucose-stimulated insulin secretion, sGSIS) is a measure of islet secretory function. The Stimulation Index (SI; insulin produced in high glucose/insulin produced in low glucose) is currently used as a product release criterion of islet transplant potency.Rese...
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BMJ Publishing Group
2024-04-01
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| Series: | BMJ Open Diabetes Research & Care |
| Online Access: | https://drc.bmj.com/content/12/2/e003897.full |
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| author | Ruth Damaris Molano Antonello Pileggi Hubert M Tse Cherie L Stabler Christopher A Fraker |
| author_facet | Ruth Damaris Molano Antonello Pileggi Hubert M Tse Cherie L Stabler Christopher A Fraker |
| author_sort | Ruth Damaris Molano |
| collection | DOAJ |
| description | Introduction Static incubation (static glucose-stimulated insulin secretion, sGSIS) is a measure of islet secretory function. The Stimulation Index (SI; insulin produced in high glucose/insulin produced in low glucose) is currently used as a product release criterion of islet transplant potency.Research design and methods Our hypothesis was that the Delta, insulin secreted in high glucose minus insulin secreted in low glucose, would be more predictive. To evaluate this hypothesis, sGSIS was performed on 32 consecutive human islet preparations, immobilizing the islets in a slurry of Sepharose beads to minimize mechanical perturbation. Simultaneous full-mass subrenal capsular transplants were performed in chemically induced diabetic immunodeficient mice. Logistic regression analysis was used to determine optimal cut-points for diabetes reversal time and the Fisher Exact Test was used to assess the ability of the Delta and the SI to accurately classify transplant outcomes. Receiver operating characteristic curve analysis was performed on cut-point grouped data, assessing the predictive power and optimal cut-point for each sGSIS potency metric. Finally, standard Kaplan-Meier-type survival analysis was conducted.Results In the case of the sGSIS the Delta provided a superior islet potency metric relative to the SI.ConclusionsThe sGSIS Delta value is predicitive of time to diabetes reversal in the full mass human islet transplant bioassay. |
| format | Article |
| id | doaj-art-a2883b83a3bc46e59f5f9b2e828927f0 |
| institution | Kabale University |
| issn | 2052-4897 |
| language | English |
| publishDate | 2024-04-01 |
| publisher | BMJ Publishing Group |
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| series | BMJ Open Diabetes Research & Care |
| spelling | doaj-art-a2883b83a3bc46e59f5f9b2e828927f02024-12-29T16:50:12ZengBMJ Publishing GroupBMJ Open Diabetes Research & Care2052-48972024-04-0112210.1136/bmjdrc-2023-003897A static glucose-stimulated insulin secretion (sGSIS) assay that is significantly predictive of time to diabetes reversal in the human islet bioassayRuth Damaris Molano0Antonello Pileggi1Hubert M Tse2Cherie L Stabler3Christopher A Fraker4Cell Transplant Center, Diabetes Research Institute, University of Miami, Coral Gables, Florida, USACell Transplant Center, Diabetes Research Institute, University of Miami, Coral Gables, Florida, USAMicrobiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, Kansas City, Kansas, USADepartment of Biomedical Engineering, University of Miami, Coral Gables, Florida, USADiabetes Research Institute, University of Miami Miller School of Medicine, Miami, Florida, USAIntroduction Static incubation (static glucose-stimulated insulin secretion, sGSIS) is a measure of islet secretory function. The Stimulation Index (SI; insulin produced in high glucose/insulin produced in low glucose) is currently used as a product release criterion of islet transplant potency.Research design and methods Our hypothesis was that the Delta, insulin secreted in high glucose minus insulin secreted in low glucose, would be more predictive. To evaluate this hypothesis, sGSIS was performed on 32 consecutive human islet preparations, immobilizing the islets in a slurry of Sepharose beads to minimize mechanical perturbation. Simultaneous full-mass subrenal capsular transplants were performed in chemically induced diabetic immunodeficient mice. Logistic regression analysis was used to determine optimal cut-points for diabetes reversal time and the Fisher Exact Test was used to assess the ability of the Delta and the SI to accurately classify transplant outcomes. Receiver operating characteristic curve analysis was performed on cut-point grouped data, assessing the predictive power and optimal cut-point for each sGSIS potency metric. Finally, standard Kaplan-Meier-type survival analysis was conducted.Results In the case of the sGSIS the Delta provided a superior islet potency metric relative to the SI.ConclusionsThe sGSIS Delta value is predicitive of time to diabetes reversal in the full mass human islet transplant bioassay.https://drc.bmj.com/content/12/2/e003897.full |
| spellingShingle | Ruth Damaris Molano Antonello Pileggi Hubert M Tse Cherie L Stabler Christopher A Fraker A static glucose-stimulated insulin secretion (sGSIS) assay that is significantly predictive of time to diabetes reversal in the human islet bioassay BMJ Open Diabetes Research & Care |
| title | A static glucose-stimulated insulin secretion (sGSIS) assay that is significantly predictive of time to diabetes reversal in the human islet bioassay |
| title_full | A static glucose-stimulated insulin secretion (sGSIS) assay that is significantly predictive of time to diabetes reversal in the human islet bioassay |
| title_fullStr | A static glucose-stimulated insulin secretion (sGSIS) assay that is significantly predictive of time to diabetes reversal in the human islet bioassay |
| title_full_unstemmed | A static glucose-stimulated insulin secretion (sGSIS) assay that is significantly predictive of time to diabetes reversal in the human islet bioassay |
| title_short | A static glucose-stimulated insulin secretion (sGSIS) assay that is significantly predictive of time to diabetes reversal in the human islet bioassay |
| title_sort | static glucose stimulated insulin secretion sgsis assay that is significantly predictive of time to diabetes reversal in the human islet bioassay |
| url | https://drc.bmj.com/content/12/2/e003897.full |
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