Growth Hormone (GH) Hypersecretion and GH Receptor Resistance in Streptozotocin Diabetic Mice in Response to a GH Secretagogue |
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| Authors: | Peter B Johansen Yael Segev Daniel Landau Moshe Phillip Allan Flyvbjerg |
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| Institution: | 1. Pharmacological Research 3, Novo Nordisk A/S, Novo Nordisk Park, Måløv, DK-2760, Denmark.;2. Molecular Endocrinology Laboratory, Department of Pediatrics, Soroka University Medical Center, Beer-Sheva, Israel.;3. Medical Department M/Medical Research Laboratory, Institute of Experimental Clinical Research, Aarhus Kommunehospital, Aarhus, Denmark, |
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| Abstract: | The growth hormone (GH) and insulin-like growth factor
I (IGF-I) axis were studied in streptozotocin (STZ) diabetic
and nondiabetic female mice following intravenous
(IV) injection of the GH secretagogue (GHS) ipamorelin or
saline. On day 14, blood samples were obtained before and
10 minutes after the injection. Livers were removed and
frozen for determination of the mRNA expressions of the
GH receptor, GH-binding protein, and IGF-I, and hepatic
IGF-I peptide. Serum samples were analyzed for GH and
IGF-I. Following ipamorelin injection, the GH levels were
found to be 150 ± 35 μg/L and 62 ± 11 μg/L in the diabetic
compared to the nondiabetic mice (P < .05). Serum IGF-I
levels were lower in diabetic than in nondiabetic animals,
and rose after stimulation only in the nondiabetic animals.
Furthermore, hepatic GH resistance and IGF-I mRNA levels
and IGF-I peptide were increased in nondiabetic animals
in response to GH stimulation, whereas the low levels per se
of all these parameters in diabetic mice were unaffected. The study shows that STZ diabetic mice demonstrate a substantial
part of the clinical features of type 1 diabetes in humans,
including GH hypersecretion and GH resistance. Accordingly,
it is proposed that STZ diabetic mice may be a better
model of the perturbations of the GH/IGF-I axis in diabetes
than STZ diabetic rats. |
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