Bioactive insulin-like growth factors as a possible molecular target for non-islet cell tumor hypoglycemia.

Non-islet cell tumor hypoglycemia (NICTH) is a paraneoplastic syndrome characterized by persistent, severe hypoglycemia with a wide variety of solid tumors. It is considered to cause hypoglycemia by increasing the insulin-like bioactivity of the circulating insulin-like growth factor (IGF) system, however, the precise mechanism of hypoglycemia remains unclear. In this manuscript, we report on a patient suffering from NICTH caused by a small cell carcinoma of the colon. This is the first report focusing on the role of bioactive IGFs for this pathological condition. First, we demonstrated that the IGF signal pathway has been activated in this tumor in an autocrine and/or paracrine manner using immunohistochemical analysis. Second, we confirmed that bioactive IGFs in the patient's serum were increased using a modified kinase receptor activation assay, thus bioactive IGFs (mainly IGF-2) could be considered to play a major pathogenic role in enhanced hypoglycemic insulin-like activity. Third, increased IGF bioactivity in the patient's serum was completely inhibited by an anti-IGF neutralizing antibody in vitro. These results suggest that neutralization of bioactive IGFs might become a novel therapeutic strategy for NICTH to relieve the hypoglycemic symptoms together with the tumor suppressive effect.

Creatine and other nonsteroidal strength-enhancing aids.

Although most discussions of ergogenic supplements to enhance strength focus on anabolic steroids, there are several nonsteroidal supplements of importance. These agents, including creatine, beta-hydroxy-beta-methylbutyrate (HMB), chromium, human growth hormone, and insulin-like growth factor are popular, easily accessible, sometimes impossible to detect, and (in some cases, ie, creatine) not banned by official sports organizations. They are purported to be natural and safe because they are not anabolic steroids, have at least a theoretic basis for potential benefit, and in some cases, have data suggesting athletic improvement in certain controlled conditions. They also have a significant potential for causing at least bothersome if not dangerous adverse effects. Studies to date have generally addressed efficacy, with little data to support effectiveness in unmonitored, uncontrolled use. Human growth hormone is officially banned. In general, none of these agents can be recommended at present.

Trophic factor supplementation: effect on the age-associated changes in body composition.

Many of the changes in body composition associated with aging are similar to those found in states of growth hormone deficiency. Elderly people have also been found to have significant abnormalities in several trophic factor systems including growth hormone/insulin-like growth factors, and both male and female sex hormones. This has led to intense interest in the clinical effects of trophic factor supplementation in older individuals. This article reviews the age-related alterations in the growth hormone and sex steroid axes, as well as the effects of supplementation. In addition, important questions about the use of trophic factors in the elderly that must be addressed in future research are put forth.