Mnich Z, Pałka J
Department of Biophysics, Medical Academy of Białystok, Białystok, Poland.
Med Sci Monit. 2001 Jan-Feb;7(1):42-8.
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.
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).
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.
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.
胰岛素样生长因子-I（IGF-I）在血清中与IGF结合蛋白（IGFBPs）结合循环，IGFBPs是IGF生物活性的重要调节剂。至少有两类结合蛋白：高分子量复合物（HMWBPs）和低分子量物质（LMWBPs），它们对IGF-I具有不同的亲和力。它们在调节IGF-I生物活性中的具体作用仍存在争议。由于：a）IGF-I在葡萄糖对抗调节中起重要作用；b）肝素被证明可改变IGF-I与结合蛋白的亲和力；c）已知禁食会改变血清结合蛋白的数量和质量，我们决定测量肝素对对照和禁食大鼠血液中IGF-I、结合蛋白和葡萄糖水平的体内影响。
在实验的3小时内，每小时给对照和禁食大鼠静脉注射肝素（500 UI/100 g体重）。在肝素注射前以及注射后15或30分钟采集血样，用于测定游离和结合的IGF-I（放射免疫分析）、结合蛋白（放射测定法）和葡萄糖水平（葡萄糖氧化酶法）。
肝素治疗在禁食大鼠中诱发低血糖，而在对照大鼠中诱发高血糖。有证据表明，肝素使IGF-I与对照大鼠血清中的HMWBPs复合物（这些动物血清中的主要复合物）解离，释放出的IGF-I继而与LMWBPs结合，LMWBPs是已知的IGF-I依赖性功能抑制剂。相反，在禁食大鼠血清中，肝素使IGF-I与LMWBPs（这些动物血清中的主要复合物）解离，使IGF-I游离并可刺激IGF-I依赖性功能。因此，在给予肝素的对照动物中，血糖水平升高，而在禁食动物中血糖水平降低。
所呈现的数据增加了以下可能性，即IGF结合蛋白可能在IGF依赖的葡萄糖对抗调节中起重要作用，并且肝素或类肝素分子可能影响这一过程。鉴于肝素在临床实践中常用，应考虑肝素诱导对照动物高血糖的医学意义。
