ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2006) 11 P254

Liver GH receptor signaling in type I diabetic mice

Lital Wachsman, Renana Eshet, Daniel Landau & Yael Segev

Ben-Gurion University, Beer-Sheva, Israel.

High levels of GH and low levels of IGF-I are found in the serum of type 1 DM. GH binds to its receptor (GHR) and leads to a series of signal transduction reactions, involving phosphorylation of intracellular proteins, including IGF-I and angiotensin II receptor type I (AT1R). It has been previously shown that in type I DM mice there is a decrease in liver GHR levels and circulating IGF-? in spite of increased circulating GH, suggesting a state of GH resistance, although its exact pathway is not clear yet. The aim of this study is to check the expression of proteins mediating GHR signalling in liver tissue of type 1 DM mice. DM was induced in adult male mice by the injection of streptozotocin (STZ). Diabetic mice (D), nondiabetic control mice (C), and control and diabetic mice injected with bovine GH, (DGH and CGH, respectively), were used. Liver tissue was examined for the following proteins (by WB): GHR, pJAK2, pSTAT5, pERK, IGF1R and AT1R. GHR and IGF-1 mRNA levels were also determined.

Results: Diabetic mice treated with or without GH, showed a significant decrease in liver GHR mRNA levels. Liver IGF-I mRNA levels were unchanged. While total STAT5 and JAK2 levels remained unchanged, the levels of phosphorylated STAT5 were increased in both CGH and DGH. Levels of IGF1R and IRS were decreased in D and DGH groups. AT1R and pERK were increased in both D and DGH groups.

In summary: GH resistance in DM is exemplified here by the decrease in liver GHR expression. The known decrease in serum IGF-I in type I DM is not supported by its unchanged liver mRNA levels. GHR signalling machinery was intact using this experimental model. The associated signalling systems with potential relevance for diabetic complications (IGF-IR and AT1R) were independently changed, irrespective of GH stimulation. The regulatory pathways involved in this depression of GHR expression in type I DM remain to be determined.

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