OBJECTIVE: To investigate the effects of leptin and the combination of insulin and leptin on glucose metabolism in incubated rat soleus muscle. ANIMALS: Male lean albino rats (50 ± 70 g) of the Wistar strain were used in all experiments. MEASUREMENTS: 2-Deoxy-D-[ 3 H]-glucose (2-DG) uptake, glycogen synthesis, lactate synthesis, glucose and pyruvate decarboxylation. RESULTS: Leptin (1, 10 and 100 nM), increased 2-Deoxyglucose uptake from 4.07 AE AE 0.23 mmolah 71 ag 71 (basal) to 5.88 AE AE 0.29 m mmolah 71 ag 71 (100 nM) (P`0.05); however, leptin did not potentiate the effect of either physiological (100 mUaml) or supra-physiological (10 000 m mUaml) insulin concentrations on glucose uptake. Glycogen synthesis rose almost 2-fold in the presence of supra-physiological leptin concentrations (100 nM). The combination of insulin and leptin did not present any additional effect on glycogen synthesis beyond that caused by insulin. Compared to the control group, the decarboxylation of [U-14 C] D-glucose increased 75%, 246% and 304% (P`0.05) in the presence of 1, 10 and 100 nM leptin, respectively. When leptin (100 nM) was combined with insulin in the incubation medium, the 14 CO 2 production rose almost 4-fold (397%) (P`0.05) and more than 5-fold (527%) (P`0.05) for the 100 m mUaml and 10 000 mUaml insulin concentrations, respectively. In the presence of leptin (100 nM), the decarboxylation of [1-14 C]-and [2-14 C]-pyruvate in incubated muscles rose 89% and 49%, respectively, indicating that both pyruvate dehydrogenase and Krebs cycle are activated by leptin. CONCLUSION: These data demonstrate that, in soleus muscle, leptin per se exerts a direct and acute insulin-like effect, stimulating glucose uptake, glycogen synthesis, lactate formation and glucose oxidation.
High pAMPK expression levels are associated with increased survival in patients with NSCLC, especially those with ADC. Our results support further evaluation of AMP-activated protein kinase as a potential prognostic and therapeutic target for lung cancer.
We conclude that leptin per se does not directly affect either liver glycolysis or its glucose production, but a physiological leptin concentration is capable of acutely inducing a direct marked reduction on the rate of glucagon-stimulated glucose production in in situ rat perfused liver. Leptin is also capable of reducing glucose production from different gluconeogenic precursors in isolated hepatocytes.
and p63) were incorporated. A nomogram was developed based on variables selected in multivariate analysis. The bootstrapping method (1000 repetitions) was applied to internally validate the nomogram Result: After a median follow-up of 32 (range, 5-122) months, disease recurrence was observed in 197(37.1%) out of the 531 patients, with a median recurrence-free survival (RFS) of 19 (95% CI, 16.63-21.37) months. Most patients (n¼136; 69.0%) had thoracic recurrence, followed by brain recurrence (n¼41; 20.8%), bone recurrence (n¼41; 20.8%), abdominal recurrence (n¼14; 7.1%), and neck recurrence (n¼13; 6.6%). Sex, tumor size, Ki67, and N stage were independent indicators of thoracic recurrence. Tumor size, N stage, CK20, and Syn were independent indicators of brain recurrence. N stage and Ki67 were independent indicators of bone recurrence. N stage was the independent indicator of abdominal recurrence and neck recurrence. Tumor size, Ki67, CK20, and N stage were independently associated with overall recurrence, and thus a nomogram predicting the 1-, 2-, and 3-year RFS probability was developed based on these four factors. The concordance index (C-index) was 0.723 (95% confidence interval, 0.675 to 0.771) and the calibration curves displayed good agreement between the predicted RFS and the actual observation. Conclusion: Independent prognostic indicators based on clinic-pathological parameters and routinely used IHC markers were identified to predict overall and site-specific recurrence, which may help to identify optimal candidates for adjuvant therapies and design individualized surveillance strategies among patients with completely resected EGFRpositive NSCLC
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