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Published on: November 5, 2016
In vivo targeted delivery of ANGPTL8 gene for beta cell regeneration in rats
Jiaxi Chen1, Shuyuan Chen, Pintong Huang
1Medical School, University of Texas Southwestern Medical Center, Dallas, TX, USA.
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.
Insights
ANGPTL8 gene therapy successfully regenerated adult and aged beta cells in rats. This approach improved glucose tolerance and insulin levels without causing severe hypertriacylglycerolaemia, offering a promising avenue for diabetes research.
Area of Science:
- Endocrinology
- Gene Therapy
- Metabolic Research
Background:
- ANGPTL8 is a hormone influencing beta cell proliferation and lipid metabolism.
- Previous studies noted ANGPTL8's potential but were limited by severe hypertriacylglycerolaemia in mice.
- The clinical utility of ANGPTL8 for beta cell regeneration requires further investigation.
Purpose of the Study:
- To investigate the therapeutic potential of ANGPTL8 gene delivery for beta cell regeneration.
- To assess the effects of ANGPTL8 on beta cell mass, glucose tolerance, and lipid metabolism in a rat model.
- To determine if ANGPTL8 gene therapy can mitigate diabetes without adverse metabolic effects.
Main Methods:
- Ultrasound-targeted microbubble destruction (UTMD) was utilized to deliver human ANGPTL8 gene plasmids.
- Gene delivery targeted the pancreas, liver, and skeletal muscle of normal adult rats.
- Streptozotocin (STZ) was used to induce a diabetes model in rats to evaluate therapeutic efficacy.
Main Results:
- Human ANGPTL8 was detected in circulation for one month post-UTMD.
- ANGPTL8 gene delivery promoted adult and aged beta cell proliferation and increased beta cell mass.
- Improved glucose tolerance, elevated fasting insulin, and absence of severe hypertriacylglycerolaemia were observed.
- ANGPTL8 gene therapy partially alleviated STZ-induced diabetes in rats.
Conclusions:
- ANGPTL8 gene therapy successfully induced adult and aged beta cell regeneration in a rat model.
- This method offers a potential strategy for managing diabetes by enhancing beta cell function.
- Further research is warranted to explore the long-term efficacy and safety of ANGPTL8-based therapies.
