The biochemical mechanisms underlying glucose-stimulated insulin secretion from pancreatic -cells are not completely understood. To identify metabolic disturbances in -cells that impair glucose-stimulated insulin secretion, we compared two INS-1-derived clonal -cell lines, which are glucose-responsive (832/13 cells) or glucose-unresponsive (832/2 cells). To this end, we analyzed a number of parameters in glycolytic and mitochondrial metabolism, including mRNA expression of genes involved in cellular energy metabolism. We found that despite a marked impairment of glucose-stimulated insulin secretion, 832/2 cells exhibited a higher rate of glycolysis. Still, no glucoseinduced increases in respiratory rate, ATP production, or respiratory chain complex I, III, and IV activities were seen in the 832/2 cells. Instead, 832/2 cells, which expressed lactate dehydrogenase A, released lactate regardless of ambient glucose concentrations. In contrast, the glucose-responsive 832/13 line lacked lactate dehydrogenase and did not produce lactate. Accordingly, in 832/2 cells mRNA expression of genes for glycolytic enzymes were up-regulated, whereas mitochondria-related genes were down-regulated. This could account for a Warburg-like effect in the 832/2 cell clone, lacking in 832/13 cells as well as primary -cells. In human islets, mRNA expression of genes such as lactate dehydrogenase A and hexokinase I correlated positively with HbA 1c levels, reflecting perturbed long term glucose homeostasis, whereas that of Slc2a2 (glucose transporter 2) correlated negatively with HbA 1c and thus better metabolic control. We conclude that tight metabolic regulation enhancing mitochondrial metabolism and restricting glycolysis in 832/13 cells is required for clonal -cells to secrete insulin robustly in response to glucose. Moreover, a similar expression pattern of genes controlling glycolytic and mitochondrial metabolism in clonal -cells and human islets was observed, suggesting that a similar prioritization of mitochondrial metabolism is required in healthy human -cells. The 832 -cell lines may be helpful tools to resolve metabolic perturbations occurring in Type 2 diabetes.Pancreatic -cells regulate whole body metabolism by secreting the hormone insulin in response to raised levels of blood glucose. However, the mechanisms underlying glucosestimulated insulin secretion (GSIS) 2 are not completely understood. The main signaling event is believed to be the rise in the ATP:ADP ratio, mainly accounted for by mitochondria. This closes ATP-dependent K ϩ (K ATP ) channels, depolarizing the plasma membrane. In turn voltage-gated Ca 2ϩ channels open, allowing Ca 2ϩ to enter the cell, initiating exocytosis of insulincontaining vesicles (1, 2). In addition, there seem to be several other metabolic events that affect insulin secretion independent of K ATP channel activity (3, 4); among them are anaplerotic rate, levels of mitochondrial glutamate, and several other metabolic intermediates (1, 5-7).Pyruvate carboxylase (PC), catalyzing the carbo...
Objectives To assess inter-modality agreement and accuracy for medial temporal lobe atrophy (MTA) ratings across radiologists with varying clinical experience in a non-demented population. Methods Four raters (two junior radiologists and two senior neuroradiologists) rated MTA on CT and MRI scans using Scheltens’ MTA scale. Ratings were compared to a consensus rating by two experienced neuroradiologists for estimation of true positive and negative rates (TPR and TNR) and over- and underestimation of MTA. Inter-modality agreement expressed as Cohen’s κ (dichotomized data), Cohen’s κw, and two-way mixed, single measures, consistency ICC (ordinal data) were determined. Adequate agreement was defined as κ/κw ≥ 0.80 and ICC ≥ 0.80 (significance level at 95% CI ≥ 0.65). Results Forty-nine subjects (median age 72 years, 27% abnormal MTA) with cognitive impairment were included. Only junior radiologists achieved adequate agreement expressed as Cohen’s κ. All raters achieved adequate agreement expressed as Cohen’s κw and ICC. True positive rates varied from 69 to 100% and TNR varied from 85 to 100%. No under- or overestimation of MTA was observed. Ratings did not differ between radiologists. Conclusion We conclude that radiologists with varying experience achieve adequate inter-modality agreement and similar accuracy when Scheltens’ MTA scale is used to rate MTA on a non-demented population. However, TPR varied between radiologists which could be attributed to rating style differences. Key Points • Radiologists with varying experience achieve adequate inter-modality agreement with similar accuracy when Scheltens’ MTA scale is used to rate MTA on a non-demented population. • Differences in rating styles might affect accuracy, this was most evident for senior neuroradiologists, and only junior radiologists achieved adequate agreement on dichotomized (abnormal/normal) ratings. • The use of an MTA scale template might compensate for varying clinical experience which could make it applicable for clinical use.
Purpose No consensus exists regarding follow-up recommendations for suspected pituitary microadenoma in children. To address this knowledge gap, we investigated the growth potential of pituitary solid and cystic lesions <10 mm in children and evaluated the accuracy of magnetic resonance imaging (MRI) measurements. Methods The children included were <18 years at first pituitary MRI and radiologically diagnosed with a non-functioning microadenoma or cyst <10 mm. Lesion size at first and latest MRI as well as all individual MRI examinations were re-evaluated. Results In total, 74 children, median age 12 years (range 3–17), had a non-functioning microadenoma, probable microadenoma, or cyst. Of these, 55 underwent repeated MRI (median 3, range 2–7) with a median follow-up of 37 months (range 4–189). None of the pituitary lesions without hormonal disturbances increased significantly during follow-up. Two radiologists agreed that no lesion could be identified in 38/269 (14%) MRI examinations, and in 51/231 (22%) they disagreed about lesion location. In 34/460 (7%) MRI measurements size differed >2 mm, which had been considered significant progression. Conclusion Non-functioning pituitary microadenoma in children has small size variations, often below the spatial resolution of the scanners. We suggest lesions <4 mm only for clinical follow-up, lesions 4–6 mm for MRI after 2 years and ≥7 mm MRI after 1 and 3 years, with clinical follow-up in between. If no progression, further MRI should only be performed after new clinical symptoms or hormonal disturbances.
Purpose Point-of-care imaging with mobile CT scanners offers several advantages, provided that the image quality is satisfactory. Our aim was to compare image quality of a novel mobile CT to stationary scanners for patients in a neurosurgical intensive care unit (ICU). Methods From November 2020 to April 2021, all patients above 18 years of age examined by a mobile CT scanner at a neurosurgical ICU were included if they also had a stationary head CT examination during the same hospitalization. Quantitative image quality parameters included attenuation and noise in six predefined regions of interest, as well as contrast-to-noise ratio between gray and white matter. Subjective image quality was rated on a 4-garde scale, by four radiologists blinded to scanner parameters. Results Fifty patients were included in the final study population. Radiation dose and image attenuation values were similar for mobCT and stationary CTs. There was a small statistically significant difference in subjective quality rating between mobCT and stationary CT images. Two radiologists favored the stationary CT images, one was neutral, and one favored mobCT images. For overall image quality, 14% of mobCT images were rated grade 1 (poor image quality) compared to 8% for stationary CT images. Conclusion Point-of-care brain CT imaging was successfully performed on clinical neurosurgical ICU patients with small reduction in image quality, predominantly affecting the posterior fossa, compared to high-end stationary CT scanners.
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