To investigate the role of insulin receptor substrate (IRS)-2 in vivo, we generated IRS-2-deficient mice by gene targeting. Although homozygous IRS-2-deficient mice (IRS-2 -/-mice) had a body weight similar to wildtype mice, they progressively developed type 2 diabetes at 10 weeks. IRS-2 -/-mice showed insulin resistance and a defect in the insulin-stimulated signaling pathway in liver but not in skeletal muscle. Despite insulin resistance, the amount of ␤-cells was reduced to 83% of that in wild-type mice, which was in marked contrast to the 85% increase in the amount of ␤-cells in IRS-1-deficient mice (IRS-1 -/-mice) to compensate for insulin resistance. Thus, IRS-2 plays a crucial role in the regulation of ␤-cell mass. On the other hand, insulin secretion by the same number of cells in response to glucose measured ex vivo was significantly increased in IRS-2 -/-mice compared with wild-type mice but was decreased in IRS-1 -/-mice. These results suggest that IRS-1 and IRS-2 may play different roles in the regulation of ␤-cell mass and the function of individual ␤-cells.

Fine-needle aspiration biopsy (FNAB) is an accurate, slightly invasive, and safe method for the preoperative diagnosis of thyroid nodules. Recently, ultrasound guidance has been suggested as a valuable aid to enhance FNAB diagnostic performance. In this study, we have compared diagnostic accuracy of conventional FNAB (C-FNAB) versus sonography-guided FNAB (SG-FNAB) on a large sample population of 9683 patients with thyroid nodules. Over a 15-year period, 4986 patients were investigated by C-FNAB and 4697 underwent SG-FNAB. A valid cytological diagnosis was obtained in 85.9% of C-FNAB and in 91.5% of SG-FNAB cases, allowing detection of thyroid cancer in 1.6% and 2.1% of patients, respectively. The indeterminate pattern of follicular neoplasia was observed in 238 C-FNAB (5%) and in 272 (5.4%) SG-FNAB nodules. Specimens were cytologically inadequate in 433 C-FNAB (8.7%), but only in 167 SG-FNAB cases (3.5%). A total of 535 C-FNAB and 540 SG-FNAB nodules underwent surgery. False-negative results occurred in 7 C-FNAB nodules (2.3%), but only in 3 SG-FNAB cases (1%). Sensitivity, specificity, and global diagnostic accuracy of C-FNAB compared with SG-FNAB were 91.8% versus 97.1%, 68.8% versus 70.9%, and 72.6% versus 75.9%, respectively. Our results, based on a large population of thyroid nodules, demonstrate that SG-FNAB allows a more precise and adequate sampling of thyroid nodular lesions and is associated with a lower rate of false-negatives, thus improving global diagnostic accuracy in the preoperative selection of thyroid cancer.

Galectin-3 (Gal-3) regulates basic cellular functions such as cell–cell and cell–matrix interactions, growth, proliferation, differentiation, and inflammation. It is not surprising, therefore, that this protein is involved in the pathogenesis of many relevant human diseases, including cancer, fibrosis, chronic inflammation and scarring affecting many different tissues. The papers published in the literature have progressively increased in number during the last decades, testifying the great interest given to this protein by numerous researchers involved in many different clinical contexts. Considering the crucial role exerted by Gal-3 in many different clinical conditions, Gal-3 is emerging as a new diagnostic, prognostic biomarker and as a new promising therapeutic target. The current review aims to extensively examine the studies published so far on the role of Gal-3 in all the clinical conditions and diseases, listed in alphabetical order, where it was analyzed.

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