Testosterone increases GLUT4-dependent glucose uptake in cardiomyocytes.

Testosterone exerts important effects in the heart. Cardiomyocytes are target cells for androgens, and testosterone induces rapid effects via Ca(2+) release and protein kinase activation and long-term effects via cardiomyocyte differentiation and hypertrophy. Furthermore, it stimulates metabolic effects such as increasing glucose uptake in different tissues. Cardiomyocytes preferentially consume fatty acids for ATP production, but under particular circumstances, glucose uptake is increased to optimize energy production. We studied the effects of testosterone on glucose uptake in cardiomyocytes. We found that testosterone increased uptake of the fluorescent glucose analog 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl)amino)-2-deoxyglucose and [(3) H]2-deoxyglucose, which was blocked by the glucose transporter 4 (GLUT4) inhibitor indinavir. Testosterone stimulation in the presence of cyproterone or albumin-bound testosterone-induced glucose uptake, which suggests an effect that is independent of the intracellular androgen receptor. To determine the degree of GLUT4 cell surface exposure, cardiomyocytes were transfected with the plasmid GLUT4myc-eGFP. Subsequently, testosterone increased GLUT4myc-GFP exposure at the plasma membrane. Inhibition of Akt by the Akt-inhibitor-VIII had no effect. However, inhibition of Ca(2+) /calmodulin protein kinase (CaMKII) (KN-93 and autocamtide-2 related inhibitory peptide II) and AMP-activated protein kinase (AMPK) (compound C and siRNA for AMPK) prevented glucose uptake induced by testosterone. Moreover, GLUT4myc-eGFP exposure at the cell surface caused by testosterone was also abolished after CaMKII and AMPK inhibition. These results suggest that testosterone increases GLUT4-dependent glucose uptake, which is mediated by CaMKII and AMPK in cultured cardiomyocytes. Glucose uptake could represent a mechanism by which testosterone increases energy production and protein synthesis in cardiomyocytes.

First report on the diagnosis and treatment of encephalic and urinary paracoccidioidomycosis in a cat.

A male Persian cat was presented with persistent fever, anorexia, weakness, hypopyon, nystagmus, and intention tremors. The hemogram showed severe neutropenia and laboratory analysis on cerebrospinal fluid (CSF) smears revealed abundant yeast cells compatible with Paracoccidioides brasiliensis. Urinalysis demonstrated persistent funguria and an increased urine protein-to-creatinine ratio (UPC) in addition to mild azotemia. Long-term therapy with oral fluconazole was effective in controlling the nervous system signs. Funguria was resolved with subcutaneous administration of diluted amphotericin B in a large volume of saline solution for a period of 12 weeks during the second year after initial diagnosis. Throughout 5 years of treatment, no adverse effects were observed and tolerance to the drugs was normal. Due to development of progressive uremic syndrome the animal was euthanased. To the best of our knowledge, this report is the first clinical case described of a nervous and urinary system infection caused by the P brasiliensis in a cat.