Editors' ChoiceDiabetes

Eavesdropping on Communications Between Liver and β Cells

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Science Translational Medicine  08 May 2013:
Vol. 5, Issue 184, pp. 184ec79
DOI: 10.1126/scitranslmed.3006452

Tissues throughout the body are in constant communication, a coordinated euphony of messages and responses to changes in metabolic and physiological states. Because so many molecular details are not well understood, scientists are keen to listen in on these communications. Yi et al. report on an important note passed between the liver and the pancreas (which can now be read aloud to the class!).

Motivated by findings that circulating factors can regulate growth and size of β cells, Yi et al. first developed a mouse model of insulin resistance—inducible by a small molecule called S961. Consistent with other insulin-resistance models, these mice showed a compensatory increase in β cell replication. Curiously, there was no detectable effect when β cells were directly exposed to S961 in vitro, suggesting that the increase in β cell replication could be an indirect effect resulting from communication promoted by other tissues. To identify candidate tissues and messages, the researchers used microarrays to analyze gene expression within key metabolic tissues in the context of a S961 perturbation. A poorly annotated gene was strongly up-regulated in liver and fat tissues—but not in β cells—in response to S961 exposure. Characterization in vivo revealed that this overexpressed gene encoded the secreted hormone betatropin, that its expression in liver specifically induced pancreatic β cell proliferation, and that betatropin-injected mice had improved glycemic control.

Although betatropin’s mechanism of action has not yet been identified, this study points to the possibility that therapeutic strategies that promote proliferation or activity of pancreatic β cells could advance diabetes treatment, augmenting (or perhaps replacing) insulin therapy. By listening closely to the conversations happening among different organs in the body, Yi et al. may have gathered an important clue to our understanding and future treatment of complex metabolic disease.

P. Yi, J.-S. Park, D. A. Melton. Betatrophin: A hormone that controls pancreatic β cell proliferation. Cell., 25 April 2013 (10.1016/j.cell.2013.04.008). [Abstract]

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