Successful β cells islet regeneration in streptozotocin-induced diabetic baboons using ultrasound-targeted microbubble gene therapy with cyclinD2/CDK4/GLP1

Chen, Shuyuan; Bastarrachea, Raúl A.; Roberts, Brad J.; Voruganti, V. Saroja; Frost, Patrice A.; Nava‐González, Edna J.; Arriaga-Cázares, Héctor Eliud; Chen, Jiaxi; Huang, Pintong; DeFronzo, Ralph A.; Comuzzie, Anthony G.; Grayburn, Paul A.

doi:10.4161/cc.27997

Cited by 33 publications

(19 citation statements)

References 24 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our data are consistent with recent studies where GLP-1 or its synthetic analogues (through GLP-1-R) engaged several downstream signaling pathways and exerted pro-survival, proliferative and, anti-apoptotic effects on human/murine islets, endothelial cells and some other tissues. 13,23,24 Also, sustained GLP-1-R activation has been shown to increase small intestine and colonic mucosal epithelium mass in rodents. 25 …”

Section: Discussionmentioning

confidence: 99%

GLP-1 nanomedicine alleviates gut inflammation

Anbazhagan

Thaqi

Priyamvada

et al. 2017

Nanomedicine: Nanotechnology, Biology and Medicine

View full text Add to dashboard Cite

The gut hormone, glucagon like peptide-1 (GLP-1) exerts anti-inflammatory effects. However, its clinical use is limited by its short half-life. Previously, we have shown that GLP-1 as a nanomedicine (GLP-1 in sterically stabilized phospholipid micelles, GLP-1-SSM) has increased in vivo stability. The current study was aimed at testing the efficacy of this GLP-1 nanomedicine in alleviating colonic inflammation and associated diarrhea in dextran sodium sulfate (DSS) induced mouse colitis model. Our results show that GLP-1-SSM treatment markedly alleviated the colitis phenotype by reducing the expression of pro-inflammatory cytokine IL-1β, increasing goblet cells and preserving intestinal epithelial architecture in colitis model. Further, GLP-1-SSM alleviated diarrhea (as assessed by luminal fluid) by increasing protein expression of intestinal chloride transporter DRA (down regulated in adenoma). Our results indicate thatGLP-1 nanomedicine may act as a novel therapeutic tool in alleviating gut inflammation and associated diarrhea in inflammatory bowel disease (IBD).

show abstract

Section: Discussionmentioning

confidence: 99%

GLP-1 nanomedicine alleviates gut inflammation

Anbazhagan

Thaqi

Priyamvada

et al. 2017

Nanomedicine: Nanotechnology, Biology and Medicine

View full text Add to dashboard Cite

show abstract

“…9 The presence of stem/progenitor cells in the duct epithelium/ lining and their contribution to endocrine cell neogenesis has been proposed by several studies dealing with pancreas injury models, [10][11][12] as well as upon transient overexpression of cyclin D2/CDK4/GLP1. 13,14 However, the contribution of duct cells to endocrine cell regeneration is challenged by additional lineage tracing experiments using different duct/centroacinar specific CreER lines, such as Hnf1B, Sox9, and Hes1. [15][16][17][18] Interestingly, a¡to-b-like cell conversion was shown to be the major mechanism underlying b-cell regeneration in condition of extreme b-cell loss 19 and in a PDL (pancreatic duct ligation) model combined with alloxan-induced b-cell ablation.…”

Section: Introductionmentioning

confidence: 99%

A genetic mouse model for progressive ablation and regeneration of insulin producing beta-cells

et al. 2014

View full text Add to dashboard Cite

The putative induction of adult b-cell regeneration represents a promising approach for the treatment of type 1 diabetes. Toward this ultimate goal, it is essential to develop an inducible model mimicking the long-lasting disease progression. In the current study, we have established a novel b-cell ablation mouse model, in which the b-cell mass progressively declines, as seen in type 1 diabetes. The model is based on the b-cell specific genetic ablation of the transcription initiation factor 1A, TIF-IA, essential for RNA Polymerase I activity (TIF-IA D/D ). Using this approach, we induced a slow apoptotic response that eventually leads to a protracted b-cell death. In this model, we observed b-cell regeneration that resulted in a complete recovery of the b-cell mass and normoglycemia. In addition, we showed that adaptive proliferation of remaining b-cells is the prominent mechanism acting to compensate for the massive b-cell loss in young but also aged mice. Interestingly, at any age, we also detected b-like cells expressing the glucagon hormone, suggesting a transition between a-and b-cell identities or vice versa. Taken together, the TIF-IA D/D mouse model can be used to investigate the potential therapeutic approaches for type 1 diabetes targeting b-cell regeneration.

show abstract

“…Two main pathways have been proposed for expanding the beta cell mass in adults [1][2][3][4][5]. The first is beta cell regeneration, which involves the replication of pre-existing beta cells in the pancreas.…”

Section: Introductionmentioning

confidence: 99%

In vivo targeted delivery of ANGPTL8 gene for beta cell regeneration in rats

Chen

Huang

et al. 2015

Diabetologia

Self Cite

View full text Add to dashboard Cite

Aims/hypothesis ANGPTL8 is a circulatory hormone secreted from liver and adipose tissue that promotes pancreatic beta cell proliferation and interferes with triacylglycerol metabolism in mice. The clinical significance of its effects on inducing beta cell proliferation is limited because it causes severe hypertriacylglycerolaemia. Methods We employed ultrasound-targeted microbubble destruction (UTMD) to deliver human ANGPTL8 gene plasmids to the pancreas, liver and skeletal muscle of normal adult rats. Results Human ANGPTL8 was consistently detected in the circulation 1 month after UTMD. ANGPTL8 gene delivery promoted the proliferation of adult and aged beta cells, expanded the beta cell mass, improved glucose tolerance and increased the fasting blood insulin level after UTMD treatment without causing severe hypertriacylglycerolaemia.ANGPTL8 gene therapy significantly alleviated but did not totally reverse STZ-induced diabetes in a rat model. Conclusions/interpretation ANGPTL8 induced adult and aged beta cell regeneration in a rat model.

show abstract

Successful β cells islet regeneration in streptozotocin-induced diabetic baboons using ultrasound-targeted microbubble gene therapy with cyclinD2/CDK4/GLP1

Cited by 33 publications

References 24 publications

GLP-1 nanomedicine alleviates gut inflammation

GLP-1 nanomedicine alleviates gut inflammation

A genetic mouse model for progressive ablation and regeneration of insulin producing beta-cells

In vivo targeted delivery of ANGPTL8 gene for beta cell regeneration in rats

Contact Info

Product

Resources

About