Successful β cells islet regeneration in streptozotocin-induced diabetic baboons using ultrasound-targeted microbubble gene therapy with cyclinD2/CDK4/GLP1
Both major forms of diabetes mellitus (DM) involve β-cell destruction and dysfunction. New treatment strategies have focused on replenishing the deficiency of β-cell mass common to both major forms of diabetes by islet transplantation or β-cell regeneration. The pancreas, not the liver, is the ide...
| Autores principales: | , , , , , , , , , |
|---|---|
| Formato: | Artículo |
| Lenguaje: | inglés |
| Publicado: |
2014
|
| Materias: | |
| Acceso en línea: | http://eprints.uanl.mx/18856/1/7.pdf |
| _version_ | 1824415366874398720 |
|---|---|
| author | Shuyuan Chen, Raúl A. Bastarrachea, Raúl A. Voruganti, Venkata Saroja Frost, Patrice A. Nava González, Edna Judith Arriaga Cazarez, Jixji Chen Huang, Pintong DeFronzo, Ralph A. Comuzzie, Anthony G. Garyburn, Paul A. |
| author_facet | Shuyuan Chen, Raúl A. Bastarrachea, Raúl A. Voruganti, Venkata Saroja Frost, Patrice A. Nava González, Edna Judith Arriaga Cazarez, Jixji Chen Huang, Pintong DeFronzo, Ralph A. Comuzzie, Anthony G. Garyburn, Paul A. |
| author_sort | Shuyuan Chen, Raúl A. |
| collection | Repositorio Institucional |
| description | Both major forms of diabetes mellitus (DM) involve β-cell destruction and dysfunction. New treatment strategies have
focused on replenishing the deficiency of β-cell mass common to both major forms of diabetes by islet transplantation
or β-cell regeneration. The pancreas, not the liver, is the ideal organ for islet regeneration, because it is the natural milieu
for islets. Since islet mass is known to increase during obesity and pregnancy, the concept of stimulating pancreatic islet
regeneration in vivo is both rational and physiologic. This paper proposes a novel approach in which non-viral gene
therapy is targeted to pancreatic islets using ultrasound targeted microbubble destruction (UTMD) in a non-human primate model (NHP), the baboon. Treated baboons received a gene cocktail comprised of cyclinD2, CDK, and GLP1, which
in rats results in robust and durable islet regeneration with normalization of blood glucose, insulin, and C-peptide levels.
We were able to generate important preliminary data indicating that gene therapy by UTMD can achieve in vivo normalization of the intravenous (IV) glucose tolerance test (IVGTT) curves in STZ hyperglycemic-induced conscious tethered
baboons. Immunohistochemistry clearly demonstrated evidence of islet regeneration and restoration of β-cell mass. |
| format | Article |
| id | eprints-18856 |
| institution | UANL |
| language | English |
| publishDate | 2014 |
| record_format | eprints |
| spelling | eprints-188562022-04-25T20:46:54Z http://eprints.uanl.mx/18856/ Successful β cells islet regeneration in streptozotocin-induced diabetic baboons using ultrasound-targeted microbubble gene therapy with cyclinD2/CDK4/GLP1 Shuyuan Chen, Raúl A. Bastarrachea, Raúl A. Voruganti, Venkata Saroja Frost, Patrice A. Nava González, Edna Judith Arriaga Cazarez, Jixji Chen Huang, Pintong DeFronzo, Ralph A. Comuzzie, Anthony G. Garyburn, Paul A. RA Aspectos Públicos de la Medicina Both major forms of diabetes mellitus (DM) involve β-cell destruction and dysfunction. New treatment strategies have focused on replenishing the deficiency of β-cell mass common to both major forms of diabetes by islet transplantation or β-cell regeneration. The pancreas, not the liver, is the ideal organ for islet regeneration, because it is the natural milieu for islets. Since islet mass is known to increase during obesity and pregnancy, the concept of stimulating pancreatic islet regeneration in vivo is both rational and physiologic. This paper proposes a novel approach in which non-viral gene therapy is targeted to pancreatic islets using ultrasound targeted microbubble destruction (UTMD) in a non-human primate model (NHP), the baboon. Treated baboons received a gene cocktail comprised of cyclinD2, CDK, and GLP1, which in rats results in robust and durable islet regeneration with normalization of blood glucose, insulin, and C-peptide levels. We were able to generate important preliminary data indicating that gene therapy by UTMD can achieve in vivo normalization of the intravenous (IV) glucose tolerance test (IVGTT) curves in STZ hyperglycemic-induced conscious tethered baboons. Immunohistochemistry clearly demonstrated evidence of islet regeneration and restoration of β-cell mass. 2014-10-02 Article PeerReviewed text en cc_by_nc_nd http://eprints.uanl.mx/18856/1/7.pdf http://eprints.uanl.mx/18856/1.haspreviewThumbnailVersion/7.pdf Shuyuan Chen, Raúl A. y Bastarrachea, Raúl A. y Voruganti, Venkata Saroja y Frost, Patrice A. y Nava González, Edna Judith y Arriaga Cazarez, Jixji Chen y Huang, Pintong y DeFronzo, Ralph A. y Comuzzie, Anthony G. y Garyburn, Paul A. (2014) Successful β cells islet regeneration in streptozotocin-induced diabetic baboons using ultrasound-targeted microbubble gene therapy with cyclinD2/CDK4/GLP1. Cell cycle, 13 (7). pp. 1145-1151. ISSN 1538-4101 (Print) 1551-4005 (Online) DOI: 10.4161/cc.27997 |
| spellingShingle | RA Aspectos Públicos de la Medicina Shuyuan Chen, Raúl A. Bastarrachea, Raúl A. Voruganti, Venkata Saroja Frost, Patrice A. Nava González, Edna Judith Arriaga Cazarez, Jixji Chen Huang, Pintong DeFronzo, Ralph A. Comuzzie, Anthony G. Garyburn, Paul A. Successful β cells islet regeneration in streptozotocin-induced diabetic baboons using ultrasound-targeted microbubble gene therapy with cyclinD2/CDK4/GLP1 |
| thumbnail | https://rediab.uanl.mx/themes/sandal5/images/online.png |
| title | Successful β cells islet regeneration in
streptozotocin-induced diabetic baboons using
ultrasound-targeted microbubble gene therapy
with cyclinD2/CDK4/GLP1 |
| title_full | Successful β cells islet regeneration in
streptozotocin-induced diabetic baboons using
ultrasound-targeted microbubble gene therapy
with cyclinD2/CDK4/GLP1 |
| title_fullStr | Successful β cells islet regeneration in
streptozotocin-induced diabetic baboons using
ultrasound-targeted microbubble gene therapy
with cyclinD2/CDK4/GLP1 |
| title_full_unstemmed | Successful β cells islet regeneration in
streptozotocin-induced diabetic baboons using
ultrasound-targeted microbubble gene therapy
with cyclinD2/CDK4/GLP1 |
| title_short | Successful β cells islet regeneration in
streptozotocin-induced diabetic baboons using
ultrasound-targeted microbubble gene therapy
with cyclinD2/CDK4/GLP1 |
| title_sort | successful β cells islet regeneration in streptozotocin induced diabetic baboons using ultrasound targeted microbubble gene therapy with cyclind2 cdk4 glp1 |
| topic | RA Aspectos Públicos de la Medicina |
| url | http://eprints.uanl.mx/18856/1/7.pdf |
| work_keys_str_mv | AT shuyuanchenraula successfulbcellsisletregenerationinstreptozotocininduceddiabeticbaboonsusingultrasoundtargetedmicrobubblegenetherapywithcyclind2cdk4glp1 AT bastarrachearaula successfulbcellsisletregenerationinstreptozotocininduceddiabeticbaboonsusingultrasoundtargetedmicrobubblegenetherapywithcyclind2cdk4glp1 AT vorugantivenkatasaroja successfulbcellsisletregenerationinstreptozotocininduceddiabeticbaboonsusingultrasoundtargetedmicrobubblegenetherapywithcyclind2cdk4glp1 AT frostpatricea successfulbcellsisletregenerationinstreptozotocininduceddiabeticbaboonsusingultrasoundtargetedmicrobubblegenetherapywithcyclind2cdk4glp1 AT navagonzalezednajudith successfulbcellsisletregenerationinstreptozotocininduceddiabeticbaboonsusingultrasoundtargetedmicrobubblegenetherapywithcyclind2cdk4glp1 AT arriagacazarezjixjichen successfulbcellsisletregenerationinstreptozotocininduceddiabeticbaboonsusingultrasoundtargetedmicrobubblegenetherapywithcyclind2cdk4glp1 AT huangpintong successfulbcellsisletregenerationinstreptozotocininduceddiabeticbaboonsusingultrasoundtargetedmicrobubblegenetherapywithcyclind2cdk4glp1 AT defronzoralpha successfulbcellsisletregenerationinstreptozotocininduceddiabeticbaboonsusingultrasoundtargetedmicrobubblegenetherapywithcyclind2cdk4glp1 AT comuzzieanthonyg successfulbcellsisletregenerationinstreptozotocininduceddiabeticbaboonsusingultrasoundtargetedmicrobubblegenetherapywithcyclind2cdk4glp1 AT garyburnpaula successfulbcellsisletregenerationinstreptozotocininduceddiabeticbaboonsusingultrasoundtargetedmicrobubblegenetherapywithcyclind2cdk4glp1 |