Type 2 diabetes mellitus (T2DM) results from insulin resistance and β-cell dysfunction, in the setting of hyperglucagonemia. Glucagon is a 29 amino acid peptide hormone, which is secreted from pancreatic α cells: excessively high circulating levels of glucagon lead to excessive hepatic glucose output. We investigated if α-cell numbers increase in T2DM and what factor (s) regulate α-cell turnover. Leprdb/Leprdb (db/db) mice were used as a T2DM model and αTC1 cells were used to study potential α-cell trophic factors. Here, we demonstrate that in db/db mice α-cell number and plasma glucagon levels increased as diabetes progressed. Insulin treatment (EC50 = 2 nM) of α cells significantly increased α-cell proliferation in a concentration-dependent manner compared to non-insulin-treated α cells. Insulin up-regulated α-cell proliferation through the IR/IRS2/AKT/mTOR signaling pathway, and increased insulin-mediated proliferation was prevented by pretreatment with rapamycin, a specific mTOR inhibitor. GcgR antagonism resulted in reduced rates of cell proliferation in αTC1 cells. In addition, blockade of GcgRs in db/db mice improved glucose homeostasis, lessened α-cell proliferation, and increased intra-islet insulin content in β cells in db/db mice. These studies illustrate that pancreatic α-cell proliferation increases as diabetes develops, resulting in elevated plasma glucagon levels, and both insulin and glucagon are trophic factors to α-cells. Our current findings suggest that new therapeutic strategies for the treatment of T2DM may include targeting α cells and glucagon.
We report two cases of myocarditis, in two young and previously healthy individuals, temporally related to the second dose of the mRNA-COVID-19 vaccine. Both patients developed acute chest pain, changes on electrocardiogram (ECG), and elevated serum troponin within two days of receiving their second dose. Cardiac magnetic resonance (CMR) findings were consistent with acute myocarditis.
hyroid nodules are an extremely common finding at US and other imaging studies (1,2). Although most thyroid nodules are benign, many patients are subjected to a costly workup that may include one or more biopsies, follow-up imaging, and even diagnostic lobectomy (3). This contributes to the overdiagnosis of thyroid cancers that are not clinically significant (4). Over the past decade, multiple groups have developed biopsy guidelines for thyroid nodules based on their appearance at US, but some guidelines are difficult to apply and all lead to high false-positive rates (benign nodules for which biopsy is recommended). With these issues in mind, a committee of the American College of Radiology (ACR) created the Thyroid Imaging Reporting and Data System (TI-RADS) to determine if thyroid nodules depicted at US require biopsy or follow-up (5). Nodules are awarded points based on features in five categories-composition, echogenicity, shape, margin, and echogenic foci. The more suspicious the feature, the higher its point value. Points are summed to categorize a nodule into one of five TI-RADS risk levels, TR1 to TR5 (Table 1). Management recommendations are determined by using the risk level and the maximum size of the nodule. The points assigned to each feature in ACR TI-RADS were based on evidence in the literature and expert consensus. Therefore, it is possible that the performance of the system could be improved by optimization of the points assigned to each US feature. Given the problem of overdiagnosis in thyroid imaging, this might improve specificity without sacrificing sensitivity. Indeed, the ACR TI-RADS committee recognized that certain features may warrant higher or lower point values to achieve optimal performance (5).
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