Interrelationship between insulin, leptin and growth hormone in growth hormone-treated children.

OBJECTIVES: The aim of the study was to examine insulin homeostasis during growth hormone (GH) therapy, and to investigate the effect of GH treatment on insulin and leptin concentration in obese children. SUBJECTS: Nineteen obese children (8 with Prader-Willi Syndrome (PWS)) were treated with GH 0.1 IU/kg/day dose for 3 months and were compared with 29 non-treated age and sex matched obese children (9 PWS) and 49 GH treated non-obese short children. Mean age of the children was 10.3+/-1.8 (6.7-13.8) y, with body mass index of 23.6+/-10.4 (11.5-47) kg/m2. RESULTS: Leptin concentration decreased and was correlated inversely with initial leptin value (r2=-0.374, P<0.001) and decreased body mass (r2=0.338, P=0.001). Insulin sensitivity index was not significantly changed during therapy. Leptin decrease after 3 months of GH administration was correlated inversely with the increase in first phase insulin response to intravenous glucose tolerance test (IVGTT) (r2=-0.595, P<0.001). Results of long-term follow-up of treated patients demonstrated a decrease in insulin concentration after cessation of therapy. In GH-treated subjects, the glucose increase in response to glucose load appeared to be higher than in untreated subjects. CONCLUSION: The high insulin response to glucose load seen in GH-treated subjects was appropriate to their glucose concentration and the insulin sensitivity index was unchanged relative to the pretreatment period. Increased insulin dosage in our patients did not induce an increase in leptin concentrations as had been hypothesised.

Molecular cloning of human brain glutamate/aspartate transporter II.

Glutamate transporters are membrane-bound proteins which are localized in glial cells and/or pre-synaptic glutamatergic nerve endings and are essential for the removal and termination of action of synaptic glutamate. Several cDNAs encoding glutamate transporters have been isolated from mammalian tissues, including human cerebellum. Here, we screened cDNA libraries derived from human brain stem and cerebellum, and isolated a novel cDNA that encodes for a glutamate transporter. This cDNA predicts a protein which contains 565 amino acids and is homologous to a rat brain Na(+)-dependent glutamate/aspartate transporter. The new cDNA is expressed in brain and is structurally distinct from the previously reported human glutamate transporter cDNA.

The Alzheimer amyloid precursor is associated with the detergent-insoluble cytoskeleton.

The amyloid beta-protein (A beta P), the main component of neuritic plaques in Alzheimer's disease (AD), is derived by unknown mechanisms from a family of amyloid precursor proteins (APPs). Using a detergent extraction procedure, we have found that in brain and in neural cell lines, 50-90% of APP is bound to detergent-insoluble cytoskeleton. Labeling experiments performed in a C6 glioma cell line indicated that both cell surface and intracellular APPs are associated with the cytoskeleton. This association requires intact microtubules and is modulated by protein phosphorylation and by cell density. These findings suggest that the function of cellular APP, presently unknown, involves the cytoskeleton and particularly microtubules. The dynamic nature of the binding and its dependence on microtubules and protein phosphorylation suggest it as a possible target in AD, where abnormal cytoskeletal structures and protein phosphorylation have been reported. Altered cytoskeletal binding of APP might lead to its aberrant proteolysis and generation of the A beta P.