The stomach is a source of leptin.

The circulating peptide leptin, which is the product of the ob gene, provides feedback information on the size of fat stores to central Ob receptors that control food intake and body-weight homeostasis. Leptin has so far been reported to be secreted only by adipocytes and the placenta. Here we show that leptin messenger RNA and leptin protein are present in rat gastric epithelium, and that cells in the glands of the gastric fundic mucosa are immunoreactive for leptin. The physiological function of this previously unsuspected source of leptin is unknown. However, both feeding and administration of CCK-8 (the biologically active carboxy-terminal end of cholecystokinin) result in a rapid and large decrease in both leptin cell immunoreactivity and the leptin content of the fundic epithelium, with a concomitant increase in the concentration of leptin in the plasma. These results indicate that gastric leptin may be involved in early CCK-mediated effects activated by food intake, possibly including satiety.

Potential role of Rab4 in the regulation of subcellular localization of Glut4 in adipocytes.

A role for Rab4 in the translocation of the glucose transporter Glut4 induced by insulin has been recently proposed. To study more directly the role of this small GTPase, freshly isolated adipocytes were transiently transfected with the cDNAs of both an epitope-tagged Glut4-myc and Rab4, a system which allows direct measurement of the concentration of Glut4 molecules at the cell surface. When cells were cotransfected with Glut4-myc and Rab4, the concentration of Glut4-myc at the cell surface decreased in parallel with the increased expression of Rab4, suggesting that Rab4 participates in the intracellular retention of Glut4. In parallel, the amount of Rab4 associated with the Glut4-containing vesicles increased. When Rab4 was moderately overexpressed, the number of Glut4-myc molecules recruited to the cell surface in response to insulin was similar to that observed in mock-transfected cells, and thus the insulin efficiency was increased. When Rab4 was expressed at a higher level, the amount of Glut4-myc present at the cell surface in response to insulin decreased. Since the overexpressed protein was predominantly cytosolic, this suggests that the cytosolic Rab4 might complex some factor(s) necessary for insulin action. This hypothesis was strengthened by the fact that Rab4 deltaCT, a Rab4 mutant lacking the geranylgeranylation sites, inhibited insulin-induced recruitement of Glut4-myc to the cell surface, even when moderately overexpressed. Rab3D was without effect on Glut4-myc subcellular distribution in basal or insulin-stimulated conditions. While two mutated proteins unable to bind GTP did not decrease the number of Glut4-myc molecules in basal or insulin-stimulated conditions at the plasma membrane, the behavior of a mutated Rab4 protein without GTPase activity was similar to that of the wild-type Rab4 protein, indicating that GTP binding but not its hydrolysis was required for the observed effects. Altogether, our results suggest that Rab4, but not Rab3D, participates in the molecular mechanism involved in the subcellular distribution of the Glut4 molecules both in basal and in insulin-stimulated conditions in adipocytes.

[Treatment of neonatal hyperthyroidism with calcium iopodate]. / Traitement de l'hyperthyroïdie néonatale par l'iopodate de calcium.

BACKGROUND: Treatment of hyperthyroidism in those neonates born to mothers with Grave's disease is difficult. Calcium ipodate, an agent for oral cholecystography, inhibits extra-thyroid conversion of T3 to T4 and diminishes thyroid secretion. CASE REPORTS: Two neonates with clinical manifestations and biological findings of hyperthyroidism were given calcium ipodate orally, 400 mg every 3 days, from day 26 to 50 for the first patient and from day 9 to 18 for the second in association with a beta blocker. Clinical manifestations disappeared within 2 days and circulating levels of T3 and T4 were normalized within 2-5 days. CONCLUSIONS: This treatment was effective and well-tolerated in both patients and in three others previously reported; it should be confirmed in a larger number of patients and controlled by measuring levels of antibodies directed against thyrotropin-releasing hormone receptors in order to avoid relapse after cessation of treatment as seen in our second patient.

GTPase activating protein activity for Rab4 is enriched in the plasma membrane of 3T3-L1 adipocytes. Possible involvement in the regulation of Rab4 subcellular localization.

The small guanosine 5'-triphosphate (GTP)ase Rab4 has been suggested to play a role in insulin-induced GLUT4 translocation. Under insulin stimulation, GLUT4 translocates to the plasma membranes, while Rab4 leaves the GLUT4-containing vesicles and becomes cytosolic. Rab proteins cycle between a GTP-bound active form and a guanosine 5'-diphosphate (GDP)-bound inactive form. The intrinsic GTPase activity of Rab proteins is low and the interconversion between the two forms is dependent on accessory factors. In the present work, we searched for a GTPase activating protein (GAP) for Rab4 in 3T3-L1 adipocytes. We used a glutathione-S-transferase (GST)-Rab4 protein which possesses the properties of a small GTPase (ability to bind GDP and GTP and to hydrolyse GTP) and can be isolated in a rapid and efficient way. This GAP activity was observed in 3T3-L1 adipocyte lysates, and was able to accelerate the hydrolysis of the [alpha-32P]GTP bound to GST-Rab4 into [alpha-32P]GDP. This activity, tentatively called Rab4-GAP, was also present in 3T3-L1 fibroblasts. The Rab4-GAP activity was present in total membrane fractions and nearly undetectable in cytosol. Following subcellular fractionation, Rab4-GAP was found to be enriched in plasma membranes when compared to internal microsomes. Insulin treatment of the cells had no effect on the total Rab4-GAP activity or on its subcellular localization. Taking our results together with the accepted model of Rab cycling in intracellular traffic, we propose that Rab4-GAP activity plays a role in the cycling between the GTP- and GDP-bound forms of Rab4, and thus possibly in the traffic of GLUT4-containing vesicles.

[Post-traumatic hypopituitarism after skull injury: apropos of 3 cases]. / Hypopituitarisme post-traumatisme crânien: à propos de trois cas.

BACKGROUND: Hypopituitarism is a rare but well-known complication of cranial trauma. In the absence of overt diabetes insipidus, its recognition is difficult as the onset of clinical symptoms can be very progressive, up to several years. CASE REPORTS: Three children, aged 8, 9 and 2 years, respectively, were admitted after a cranial trauma. Manifestations of diabetes insipidus occurred a few days later in two patients; one of them developed secondary growth hormone deficiency, hypothyroidism and hypogonadism, only evidenced at the age of 14 years. The third patient also developed manifestations of hypothalamic and/or pituitary hormone deficiencies without diabetes insipidus at the age of 12 years-6 months. MRI showed complete severance of the pituitary stalk in two patients and absence of posterior pituitary signal in one of the two patients with diabetes insipidus. CONCLUSION: Growth disorders and/or hypogonadism may occur many years after a trauma that may have been forgetten. Search for such an etiology and dynamic MRI are necessary in identifying heterogenous hypophyseal lesions.