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Heparin-induced modulation of insulin like-growth factor-I action on glucose level in control and fasted rats
Background:
Insulin like-growth factor-I (IGF-I) circulates in serum bound to IGF-binding proteins (IGFBPs), which are important regulators of IGF's biological activity. There are at least two classes of BPs: a high molecular weight complex (HMWBPs) and low molecular weight species (LMWBPs), with different affinity for IGF-I. Their specific role in regulation of IGF-I bioactivity is still controversial. Since: a) IGF-I plays an important role in glucose counter regulation; b) heparin was shown to alter IGF-I affinity to BPs; and c) fasting is known to change quantity and quality of serum BPs, we decided to measure the in vivo effect of heparin on blood IGF-I, BPs and glucose levels in control and fasted rats.
Materials And Methods:
Control and fasted rats were injected i.v. with heparin (500 UI/100 g body weight) every hour during 3 hours of the experiment. Blood samples were collected before and 15 or 30 minutes after heparin injection and used for determination of free and bound IGF-I (RIA), BPs (radiometric assay) and glucose level (glucose oxidase method).
Results:
Heparin treatment induced hypoglycaemia in fasted rats while it induced hyperglycemia in control one. The evidence was provided that heparin dissociates IGF-I from HMWBPs complex of control rat serum (predominant one in serum of these animals) and released IGF-I in turn is bound to LMWBPs--known as inhibitors of IGF-I dependent functions. In contrast, in fasted rat serum heparin dissociates IGF-I from LMWBPs (predominant complex in serum of these animals) making IGF-I free and available to stimulate IGF-I dependent functions. Therefore in control animals, which were administered heparin, blood glucose level was elevated and in fasted animals it was decreased.
Conclusions:
The data presented raise the possibility that IGF-BPs may have an important role in IGF-dependent glucose counter regulation and that heparin or heparin-like molecules may affect the process. Medical significance of heparin-induced hyperglycaemia in control animals should be taken into consideration since heparin is commonly used in clinical practice.