Linköping University

About: Linköping University is a education organization based out in Linköping, Sweden. It is known for research contribution in the topics: Population & Thin film. The organization has 15671 authors who have published 50013 publications receiving 1542189 citations.

Attenuated mTOR signaling and enhanced autophagy in adipocytes from obese patients with type 2 diabetes.

Abstract: Type 2 diabetes (T2D) is strongly linked to obesity and an adipose tissue unresponsive to insulin. The insulin resistance is due to defective insulin signaling, but details remain largely unknown. We examined insulin signaling in adipocytes from T2D patients, and contrary to findings in animal studies, we observed attenuation of insulin activation of mammalian target of rapamycin (mTOR) in complex with raptor (mTORC1). As a consequence, mTORC1 downstream effects were also affected in T2D: feedback signaling by insulin to signal-mediator insulin receptor substrate-1 (IRS1) was attenuated, mitochondria were impaired and autophagy was strongly upregulated. There was concomitant autophagic destruction of mitochondria and lipofuscin particles, and a dependence on autophagy for ATP production. Conversely, mitochondrial dysfunction attenuated insulin activation of mTORC1, enhanced autophagy and attenuated feedback to IRS1. The overactive autophagy was associated with large numbers of cytosolic lipid droplets, a subset with colocalization of perlipin and the autophagy protein LC3/atg8, which can contribute to excessive fatty acid release. Patients with diagnoses of T2D and overweight were consecutively recruited from elective surgery, whereas controls did not have T2D. Results were validated in a cohort of patients without diabetes who exhibited a wide range of insulin sensitivities. Because mitochondrial dysfunction, inflammation, endoplasmic-reticulum stress and hypoxia all inactivate mTORC1, our results may suggest a unifying mechanism for the pathogenesis of insulin resistance in T2D, although the underlying causes might differ.0

Lysosomes in iron metabolism, ageing and apoptosis

Abstract: The lysosomal compartment is essential for a variety of cellular functions, including the normal turnover of most long-lived proteins and all organelles. The compartment consists of numerous acidic vesicles (pH ∼4 to 5) that constantly fuse and divide. It receives a large number of hydrolases (∼50) from the trans-Golgi network, and substrates from both the cells’ outside (heterophagy) and inside (autophagy). Many macromolecules contain iron that gives rise to an iron-rich environment in lysosomes that recently have degraded such macromolecules. Iron-rich lysosomes are sensitive to oxidative stress, while ‘resting’ lysosomes, which have not recently participated in autophagic events, are not. The magnitude of oxidative stress determines the degree of lysosomal destabilization and, consequently, whether arrested growth, reparative autophagy, apoptosis, or necrosis will follow. Heterophagy is the first step in the process by which immunocompetent cells modify antigens and produce antibodies, while exocytosis of lysosomal enzymes may promote tumor invasion, angiogenesis, and metastasis. Apart from being an essential turnover process, autophagy is also a mechanism by which cells will be able to sustain temporary starvation and rid themselves of intracellular organisms that have invaded, although some pathogens have evolved mechanisms to prevent their destruction. Mutated lysosomal enzymes are the underlying cause of a number of lysosomal storage diseases involving the accumulation of materials that would be the substrate for the corresponding hydrolases, were they not defective. The normal, low-level diffusion of hydrogen peroxide into iron-rich lysosomes causes the slow formation of lipofuscin in long-lived postmitotic cells, where it occupies a substantial part of the lysosomal compartment at the end of the life span. This seems to result in the diversion of newly produced lysosomal enzymes away from autophagosomes, leading to the accumulation of malfunctioning mitochondria and proteins with consequent cellular dysfunction. If autophagy were a perfect turnover process, postmitotic ageing and several age-related neurodegenerative diseases would, perhaps, not take place.

Patient satisfaction in relation to age, health status and other background factors: a model for comparisons of care units

Abstract: Objective. To analyse the relationship between patient satisfaction and background factors such as age, gender, health status and pain. In addition, to use background factors to create less biased ranking in comparisons of patient satisfaction between medical specialities. Design. A questionnaire was sent by post to patients who had recently received inpatient care at a hospital within the County of Ostergotland, Sweden. The questionnaire contained 33 questions, 21 of which concerned the quality of health care and patient satisfaction. Setting. Inpatient departments at all four hospitals in the County of Ostergotland, Sweden. Subjects. All patients discharged from the hospital during a period of 6 weeks. Approximately 3400 patients aged 1-94 years responded to the questionnaire, resulting in a response rate of 69%. Main outcome measures. Patient satisfaction index score (PSI). Results. Of the background factors tested, patient age had the greatest explanatory value regarding the PSI, closely followed by experiencing anxiety during admission. With regard to variations in the PSI, about 20% could be explained by the background factors taken as a whole. Gender did not correlate with the PSI, although males were somewhat more satisfied than females. PSI scores differed among medical specialities and, interestingly, when age and other background factors were controlled for, the picture changed regarding the medical speciality that received the best PSI score. Conclusion. The change in ranking among medical specialities after adjustment for background factors emphasizes the importance of including background factors in patient satisfaction analyses in order to obtain less biased comparisons.