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There are different results related to betatrophin and its characteristic to induce insulin and/or expand the pancreas beta cells. All the experiments so far were performed in mice. Some of the authors like Elisabeth Kugelberg from Harvard University agrees that betatrophin can induce insulin and expansion of secreting beta cells in mice (E. Kugelberg , 2014). Levitsky et al., 2014, come to the conclusion that betatrophin stimulate growth of beta cells in mice, while Gusarova et al., 2014, said that Betatrophin doesn’t control cell expansion in mice ( Gusarova et al., 2014) All three results are based on experiments on mice.

To make sure what are the characteristics of betatrophin in human pancreatic beta cells I suggest to try to determine the concentration and effect on those concentrations on immortal beta cells from human, CM cell line (insulinoma-obtained from ascitic fluid of cancer patients ) ( they are not producing any insulin under the glucose stimulation, therefore they may be a good for our model if they respond to betatrophin) TRM-1 (foetal Human SV40 T antigen)-Express small amount of insulin, not responsive to glucose stimulation) and finally Blox5 ( foetal Human SV40 T –antigen) which Exhibit glucose responsive. and Low insulin content. Blox5 may be the second good cell line to experiment, because they are responsive to glucose and they may be responsive to betatrophin as well.

If we found that those cell lines are inducing insulin then we may try primary beta cells. There is an article of 2013 (Ilie and Ilie, 2013) in which there is a possibility of regeneration of beta cells in vivo by neogenesis from adult pancreas. We can use their model to see if betatrophin indeed induce insulin in those cells. ( see the article attached)

On the other hand there are possibilities of growing beta cells directly onto pancreatic duct as it shows below:

From: https://infodiabet.wordpress.com/2010/08/31/new-sources-of-pancreatic-beta-cells/

Therefore, I suggest of producing pancreatic duct by using 3D printing and grow the cells by neogenesis

directly on the pancreatic duct.

References:

Gusarova V, Alexa CA, Na E, Stevis PE, Xin Y, Bonner-Weir S,

Cohen JC, Hobbs HH, Murphy AJ, Yancopoulos GD, Gromada J (2014), ANGPTL8/Betatrophin Does Not Control Pancreatic Beta Cell Expansion. Cell 159: 691-696.

Kugelberg E. (2013) Diabetes: Betatrophin—inducing β-cell expansion to treat diabetes mellitus? Nature Reviews Endocrinology 9: 379

Levitsky LL, Ardestani G, Rhoads DB (2014). Role of growth factors in control of pancreatic beta cell mass: focus on betatrophin. Curr Opin Pediatr. August 26 (4):475-9