The activation of the glucagon-like peptide-1 (GLP-1) receptor has been shown to have an important role in the functional activity of islet beta-cells and in the expansion of the islet cell mass. Constant remodeling of islet cell mass is mediated in vivo by proliferative and apoptotic stimuli to ensure a dynamic response to a changing demand for insulin. The present study was undertaken to investigate the biological activity of GLP-1 when cells were challenged by a proapoptotic stimulus. We have shown that activation of the GLP-1 receptor inhibits H(2)O(2)-induced apoptosis in a cultured mouse insulinoma cell line, termed MIN6. GLP-1 reduced DNA fragmentation and improved cell survival. This was mediated by an increased expression of the antiapoptotic proteins Bcl-2 and Bcl-xL. GLP-1 also prevented the H(2)O(2)-dependent cleavage of poly-(ADP-ribose)-polymerase. Inhibition of the GLP-1-dependent increase of cAMP by Rp-cAMP blocked the antiapoptotic action of GLP-1, as determined by DNA fragmentation and poly-(ADP-ribose)-polymerase assays and by detection of Bcl-2 and Bcl-xL protein levels. Investigation of the role of the protein kinases, PI-3 kinase (PI3K) and MAPK, by use of the inhibitors PD098059 and LY294002 demonstrated that the activation of PI3K, but not MAPK, was required to prevent proapoptotic events in cells exposed to H(2)O(2). The present study provides evidence that GLP-1 has an antiapoptotic action mediated by a cAMP- and PI3K-dependent signaling pathway.

No abstract

A 59-year-old African American male with a remote history of Graves' disease presented with a 13-cm sacrococcygeal mass that was resected. Pathologic examination revealed this to be papillary thyroid carcinoma with large areas of hemorrhage and necrosis. No other teratomatous elements were identified. The patient underwent extensive evaluation of the thyroid gland with ultrasound, computed tomography (CT) scan, and laboratory studies without any evidence of thyroid mass or malignancy. In addition, further evaluations with chest/abdominal/pelvic CT as well as a bone scan failed to reveal any evidence of metastatic disease. At 1-year follow-up, the patient has remained euthyroid and without evidence of recurrence. We believe that our patient may represent the first reported case of malignant transformation of mature thyroid tissue in a sacrococcygeal teratoma. The impact of his diagnosis on the decision-making for performing a total thyroidectomy is discussed.