Incretin receptors in non-neoplastic and neoplastic thyroid C cells in rodents and humans: relevance for incretin-based diabetes therapy

While incretins are of great interest for the therapy of diabetes 2, the focus has recently been brought to the thyroid, since rodents treated with glucagon-like peptide-1 (GLP-1) analogs were found to occasionally develop medullary thyroid carcinomas. Incretin receptors for GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) were therefore measured in various rodent and human thyroid conditions. In vitro GLP-1 and GIP receptor autoradiography were performed in normal thyroids, C-cell hyperplasia and medullary thyroid carcinomas in rodents. Receptor incidence and density were assessed and compared with the receptor expression in human thyroids, medullary thyroid carcinomas, and TT cells. GLP-1 receptors are expressed in C cells of normal rat and mice thyroids. Their density is markedly increased in rat C-cell hyperplasia and medullary thyroid carcinomas, where their incidence amounts to 100%. GIP receptors are neither detected in normal rodent thyroids nor in C-cell hyperplasia, but are present in all rat medullary thyroid carcinomas. No GLP-1 or GIP receptors are detected in normal human thyroids. Whereas only 27% of all human medullary thyroid carcinomas express GLP-1 receptors, up to 89% express GIP receptors in a high density. TT cells lack GLP-1 receptors but express GIP receptors. GLP-1 receptors are frequently expressed in non-neoplastic and neoplastic C cells in rodents while they are rarely detected in human C-cell neoplasia, suggesting species differences. Conversely, GIP receptors appear to be massively overexpressed in neoplastic C cells in both species. The presence of incretin receptors in thyroid C cell lesions suggests that this organ should be monitored before and during incretin-based therapy of diabetes

Nematic Ordering Pattern Formation in the Process of Self-Organization of Microtubules in a Gravitational Field

Papaseit et al. (Proc. Natl. Acad. Sci. U.S.A. 97, 8364, 2000) showed the decisive role of gravity in the formation of patterns by assemblies of microtubules in vitro. By virtue of a functional scaling, the free energy for MT systems in a gravitational field was constructed. The influence of the gravitational field on MT’s self-organization process, that can lead to the isotropic to nematic phase transition, is the focus of this paper. A coupling of a concentration gradient with orientational order characteristic of nematic ordering pattern formation is the new feature emerging in the presence of gravity. The concentration range corresponding to a phase coexistence region increases with increasing g or MT concentration. Gravity facilitates the isotropic to nematic phase transition leading to a significantly broader transition region. The phase transition represents the interplay between the growth in the isotropic phase and the precipitation into the nematic phase. We also present and discuss the numerical results obtained for local MT concentration change with the height of the vessel, order parameter and phase transition properties