The liver-specific glucokinase knockout (gck^w/–) mouse experiences long-term hyperglycemia and insulin resistance. This study was designed to evaluate the functional and structural changes in the myocardium of 60 week-old gck^w/– mice, and to investigate the effect of rosiglitazone on the myocardium in this model. 60 week-old gck^w/– mice were randomly divided into 3 groups: gck^w/–, gck^w/– mice treated with insulin (1 U/kg) and gck^w/– mice treated with rosiglitazone (18 mg/kg). Insulin or rosiglitazone treatment was for 4 weeks. Gck^w/w litermates were used as controls. Echocardiography, electrocardiogram, biochemical, histopathological, ultrastructural, real time PCR and Western blot studies were performed to examine for structural and functional changes. Long-term liver-specific gck knockout in mice elicits hyperglycaemia and insulin resistance. Compared to age matched gck^w/w mice, 60 week-old gck^w/– mice showed decreased LV internal dimension, increased posterior wall thickness, lengthened PR and QRS intervals, up-regulated MLC2 protein expression, decreased SOD activity, increased MDA levels and up-regulated Cyba mRNA. Morphological studies revealed that there was an increase in the amount of PAS and Masson positively stained material, as did the number and proportion of the cell occupied by mitochondria in the gck^w/– mice. Western blot analysis revealed that the levels of the insulin receptor, Akt, phosphorylated AMPK beta and phosphorylated ACC were reduced in gck^w/– mice. These effects were partly attenuated or ablated by treatment with rosiglitazone. Our results indicate that changes in the myocardium occur in the liver-specific glucokinase knockout mouse and suggest that reduced glucokinase expression in the liver may induce diabetic cardiomyopathy by up regulating NADPH oxidase and down regulating insulin receptor and p-AMPK protein levels. Rosiglitazone treatment may protect against diabetic cardiomyopathy by altering the levels of a set of proteins involved in cardiac damage.

Liver glucokinase (GCK) deficient mice possess mild renal complications associated with diabetes. To investigate the progression of kidney disease and identify candidate genes involved in the pathogenesis of renal damage, we examined changes in tissue structure and gene expression in the kidneys of liver-specific GCK knockout (gck^w/−) mice and age-matched normal wild-type control (gck^w/w) mice as they aged. Suppression subtractive hybridization (SSH) was used to identify candidate genes that showed a pattern of differential expression between kidneys of gck^w/− and gck^w/w mice at 60 weeks of age. Differential expression of the candidate genes was examined by real-time qPCR in liver-specific gck^w/− and gck^w/w mice at 16, 26, 40, 60, and 85 weeks of age. Among the candidate genes, only glutathione peroxidase-3 (GPX3) was confirmed to show differential expression by qPCR in the 60-week old mice, however two others genes, MALAT1 and KEG, showed significant changes at other ages. This study shows that liver-specific glucokinase deficient mice display changes in kidney morphology by 40 weeks of age, and that renal complication may be correlated with a reduction in GPX3 levels. Since decreased GPX3 mRNA expression was observed at 26 weeks, which is younger than the age when pathological changes can be seen in kidney biopsies, GPX3 may serve as an early marker for kidney damage.

Background: This study aimed to investigate the relationship between echocardiography results and lung ultrasound score (LUS) in coronavirus disease 2019 (COVID-19) pneumonia patients and evaluate the impact of the combined application of these techniques in the evaluation of COVID-19 pneumonia. Methods: Hospitalized COVID-19 pneumonia patients who underwent daily lung ultrasound and echocardiography were included in this study. Patients with tricuspid regurgitation within three days of admission were enrolled. Moreover, the correlation and differences between their pulmonary artery pressure (PAP) and LUS on days 3, 8, and 13 were analyzed. The inner diameter of the pulmonary artery root as well as the size of the atria and ventricles were also considered. Results: The PAP on days 3, 8, and 13 of hospitalization was positively correlated with the LUS (r = 0.448, p = 0.003; r = 0.738, p < 0.001; r = 0.325, p = 0.036, respectively). On day 8, the values of both PAP and LUS were higher than on days 3 and 13 (p < 0.01). Similarly, PAP and LUS were significantly increased in 92.9% (39/42) and 90.5% (38/42) of patients, respectively, and at least one of these two values was positive in 97.6% (41/42) of cases. The inner diameters of the right atrium, right ventricle, and pulmonary artery also differed significantly from their corresponding values on days 3 and 13 (p < 0.05). Conclusions: PAP is positively correlated with LUS in COVID-19 pneumonia. The two values could be combined for a more precise assessment of disease progression and recovery status.