Pancreatic Beta Cell Proliferation & Hyperplasia
- 详细技术说明
- This invention relates to treatingdiabetes via the transplantation of cells depleted of Toll-like Receptors 2 and4.
- *Abstract
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Approximately29.1 million people in the U.S. are living with diabetes in 2012 with Type 1 andType 2 diabetes accounting for approximately 5% and 95% of all cases,respectively.
Pancreatic beta cells are critical in maintaining glucose levels bysecreting insulin and beta cell dysfunction is a core cause of the disease and itsprogression.
Cornell researchers have discovered that Toll-like Receptors 2 and 4(TLR2 and TLR4) are directly implicated in regulating beta cell proliferationand size. Specifically, when TLR2 andTLR4 are disrupted simultaneously in primary islets, beta cell proliferation isdramatically increased.
Experiments showed the positive effect of silencingboth TLR2 and TLR4 in beta cells in double knockout mice (DKO) as evidenced by(i) insulin levels, glucose tolerance, and beta cell mass (Fig.1), and (ii) proliferation of beta cells (Fig.2).
Figure 1. Synergistic effect of TL2 and TL4 deficiency in HFD-fed mice (high-fat diet) vs LFD-fed (low-fat diet).
Figure 2. Beta cell proliferation in WT and DKO miceunder HFD and LFD.
Researchersalso showed that the effect of TLR2/TLR4 DKO is a cell autonomous effect,independent of soluble factors, whichwill enable improved treatment of diabetes, including by transplantation ofTLR2/TLR4 DKO islet cells.
PotentialApplications
Treatment for type-1and type-2 diabetes.
Advantages
- Improvedinsulin sensitivity
- Pancreaticbeta cell proliferation with an increase in cell mass
- Cell-autonomousmechanism allows for transplantation strategy
- Islet-producingstems cells or non-pancreatic cells (e.g. liver cells, comprising the combinedsteps of inducing PDX-1 gene expression), can also be used.
- *Licensing
- Phillip Owhpo62@cornell.edu1-607-254-4508
- 其他
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- Patent allowed in the U.S. US2017/0342097
- Y. Ji, et al. (2017). Toll-like receptors 2 and4 act as brakes for adaptive beta cell expansion in diet-induced obesity. Submitted.
- 国家/地区
- 美国
