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Objective
Obesity contributes to insulin resistance and is a risk factor for diabetes. C-terminal modulator protein (CTMP) and leucine zipper/EF-hand-containing transmembrane protein 1 (LETM1) have been reported to influence the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB) signaling pathway via the modulation of PKB activity, a key player for insulin signaling. However, it remains unclear whether CTMP and LETM1 are associated with PI3K/PKB signaling in mouse models of obesity.Materials/Methods
To address this question, we used two different mouse models of obesity, including high-fat diet (HFD)-induced diabetic mice and genetically modified obese mice (ob/ob mice). The levels of insulin-signaling molecules in these mice were determined by immunohistochemical and Western blot analyses. The involvement of CTMP and LETM1 in PI3K/PKB signaling was investigated in HEK293 cells by transient transfection and adenovirus-mediated infection.Results
We found that the levels of insulin receptor, phosphorylated PKB, and LETM1 were lower and the level of CTMP was higher in the adipose tissue of obese mice on an HFD compared to lean mice on a chow diet. Similar results were obtained in ob/ob mice. In HEK293 cells, the activation of PKB increased the LETM1 level, and inhibition of PKB increased the CTMP level. The overexpression of CTMP suppressed the insulin-induced increase in PKB phosphorylation, which was abrogated by co-overexpression with LETM1.Conclusion
These results suggest that CTMP and LETM1 may participate in impaired insulin signaling in the adipose tissue of obese mice, raising the possibility that these parameters may serve as new candidate biomarkers or targets in the development of new therapeutic approaches for diabetes. 相似文献The most common abnormal spirometric pattern reported in WTC worker and volunteer cohorts has consistently been that of a nonobstructive reduced forced vital capacity (low FVC). Low FVC is associated with obesity, which is highly prevalent in these cohorts. We used quantitative CT (QCT) to investigate proximal and distal airway inflammation and emphysema in participants with stable low FVC pattern.
MethodsWe selected study participants with at least two available longitudinal surveillance spirometries, and a chest CT with QCT measurements of proximal airway inflammation (wall area percent, WAP), end-expiratory air trapping, suggestive of distal airway obstruction (expiratory to inspiratory mean lung attenuation ratio, MLAEI), and emphysema (percentage of lung volume with attenuation below − 950 HU, LAV%). The comparison groups in multinomial logistic regression models were participants with consistently normal spirometries, and participants with stable fixed obstruction (COPD).
ResultsCompared to normal spirometry participants, and after adjusting for age, sex, race/ethnicity, BMI, smoking, and early arrival at the WTC disaster site, low FVC participants had higher WAP (ORadj 1.24, 95% CI 1.06, 1.45, per 5% unit), suggestive of proximal airway inflammation, but did not differ in MLAEI, or LAV%. COPD participants did not differ in WAP with the low FVC ones and were more likely to have higher MLAEI or LAV% than the other two subgroups.
DiscussionWTC workers with spirometric low FVC have higher QCT-measured WAP compared to those with normal spirometries, but did not differ in distal airway and emphysema measurements, independently of obesity, smoking, and other covariates.
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