Growth hormone (GH) hypersecretion and GH receptor resistance in streptozotocin diabetic mice in response to a GH secretagogue.
Johansen. Peter B PB; Segev. Yael Y; Landau. Daniel D; Phillip. Moshe M; Flyvbjerg. Allan A
Key Findings
- Ipamorelin injection raised GH levels much higher in diabetic mice than in healthy mice.
- Serum IGF‑1 increased only in healthy mice after ipamorelin; diabetic mice showed no rise.
- Liver GH‑receptor activity and IGF‑1 production were up‑regulated in healthy mice but remained low in diabetic mice, indicating GH resistance.
Practical Outcomes
- For most biohackers who are not insulin‑deficient, ipamorelin can still be expected to raise GH, but the downstream IGF‑1 boost may be limited if insulin signaling is impaired. This study mainly reinforces existing knowledge rather than offering new dosing tips. It suggests monitoring insulin status when using GH secretagogues for optimal IGF‑1 benefits.
Summary
In mice without insulin (a model of type 1 diabetes), the GH‑releasing peptide ipamorelin caused a big jump in growth hormone levels, but the liver didn't respond by making more IGF‑1, showing a kind of GH resistance. Normal mice did increase IGF‑1 after the same dose. This suggests that the hormone‑boosting effect of ipamorelin depends on having normal insulin signaling.
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 microg/L and 62 +/- 11 microg/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.
Study Information
pubmed
2003
10.1155/edr.2003.73