Transgenic insulin released from G cells preferentially signals in the liver.
We have previously produced transgenic G-InsKi mice, a model allowing regulated portal insulin delivery from gastric G cells without using beta cells. Here, we report that in G-InsKi mice portal levels of transgenic human insulin are 6-fold higher than in peripheral circulation. Peptone-induced release of transgenic human insulin from G cells preferentially stimulated signaling cascades in the liver rather than in peripheral insulin-sensitive tissues, as judged by tyrosine phosphorylation of insulin receptor beta subunit and phosphorylation of protein kinase Akt/PKB at Thr-308. G-InsKi mice provide a novel animal model for elucidating direct effects of insulin on liver functions.
Lu
Yu-Chun
YC
Department of Medicine, Division of Digestive Diseases, David Geffen School of Medicine at UCLA and CURE: Digestive Diseases Research Center, Los Angeles, CA 90095, USA.
Rozengurt
Enrique
E
Zhukova
Elena
E
D000818:Animals; D018076:DNA, Complementary / Q000235:genetics; D004435:Eating; D019863:Gastrin-Secreting Cells / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D011972:Receptor, Insulin / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction
D018076:DNA, Complementary; D007328:Insulin; D011994:Recombinant Proteins; D011972:Receptor, Insulin