Peroxisome proliferator-activated receptor (PPAR)-gamma ligands are insulin sensitizers, widely used in the treatment of type 2 diabetes. A consistent observation in preclinical species is the development of cardiac hypertrophy after short-term treatment with these agents. The mechanisms for this hypertrophy are incompletely understood. Given the important role of insulin signaling in the regulation of myocardial size, we tested the hypothesis that augmentation of myocardial insulin signaling may play a role in PPAR-gamma ligand-induced cardiac hypertrophy. We treated mice with cardiomyocyte-restricted knockout of insulin receptors (CIRKO) and littermate controls (wild type) with 2-(2-(4-phenoxy-2-propylphenoxy) ethyl) indole-5-acetic acid (COOH), which is a non-thiazolidinedione PPAR-gamma agonist for 2 wk. Two weeks of COOH treatment increased heart weights by 22% in CIRKO mice and 16% in wild type, and induced similar fold increase in the expression of hypertrophic markers such as alpha-skeletal actin, brain natriuretic peptide, and atrial natriuretic peptide in CIRKO and wild-type (WT) hearts. COOH treatment increased plasma volume by 10% in COOH-treated WT and CIRKO mice but did not increase systolic or diastolic blood pressure. Echocardiographic analysis was also consistent with volume overload, as evidenced by increased left ventricular diastolic diameters and cardiac output in COOH-treated CIRKO and WT mice. These data indicate that cardiac hypertrophy after PPAR-gamma agonist treatment can occur in the absence of myocardial insulin signaling and is likely secondary to the hemodynamic consequences of plasma volume expansion.
Historically, cranial nerves have been a problematic subject for medical students to learn. Although there are an abundance of illustrations and depictions available, a challenge medical students face is to understand systemically how each cranial nerve relates to one another. To help address this problem, a cranial nerve (CN) tutorial was created. We demonstrated all twelve pairs of cranial nerves together in one illustration using macromedia flash. The interactive program was posted on our anatomy website. The CN tutorial allowed students to explore individual cranial nerves on one diagram, as well as pathways, foramina, modalities, and regional innervation. In addition to these illustrations, students tested their knowledge tracing modalities, pathways, and quizzing autonomously within the CN template. As a result, a template was developed enabling students to independently study the cranial nerves in relation to each other. At the conclusion of the course, a short questionnaire was administered concerning the effectiveness of the cranial nerve tutorial. We received positive feedback.
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