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VOL. 76 (1), 23-44, 2010 BETA-CELL HYPERPLASIA INDUCED BY HEPATIC INSULIN...

In conclusion, our results showed that a defect in the liver leads
to an overall insulin resistance. Given the fact that insulin resistance
states course with compensatory beta-cell hyperplasia, iLIRKO
studies have pointed out a cause and effect relationship between
progressive insulin resistance and beta-cell hyperplasia. Ultimately,
the beta cells could undergo a failure in the insulin secretion that
leads to uncontrolled diabetes. Thus, in these mice, isolated hepatic
insulin resistance is sufficient to recapitulate the progressive
pathogenesis of type 2 diabetes. In this context, iLIRKO mice
induced IGF-1 expression in parallel to IR deletion in the liver. This
resulted in a persistent increase of circulating IGF-1. Concurrently,
there was a huge increase of IR-A in the total percentage of IR in the
hyperplastic pancreatic islets from iLIRKO mice. Thus, our results
in iLIRKO mice suggest a liver-pancreatic endocrine axis, IGF-1
being a liver factor that might contribute to compensatory beta-cell
hyperplasia through IR-A.

5. ACKNOWLEDGEMENTS

This work was supported by grants SAF2005/00014 and SAF2007/
60058, from Ministerio de Educación y Ciencia and Red Temática de
Investigación Cooperativa en Diabetes RD06/0015/0005, from Insti-
tuto de Salud Carlos III, Ministerio de Sanidad y Consumo, Spain.
We gratefully acknowledge the technical expertise of Dr. J. A. López
García-Asenjo, Surgery Pathology Branch, Hospital Clínico San Car-
los, Madrid, Spain.

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