| 1. |
- Solinas, Giovanni, et al.
(författare)
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An adipoincretin effect links adipostasis with insulin secretion.
- 2024
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Ingår i: Trends in endocrinology and metabolism: TEM. - 1879-3061. ; 35:6, s. 466-477
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Forskningsöversikt (refereegranskat)abstract
- The current paradigm for the insulin system focuses on the phenomenon of glucose-stimulated insulin secretion and insulin action on blood glucose control. This historical glucose-centric perspective may have introduced a conceptual bias in our understanding of insulin regulation. A body of evidence demonstrating that in vivo variations in blood glucose and insulin secretion can be largely dissociated motivated us to reconsider the fundamental design of the insulin system as a control system for metabolic homeostasis. Here, we propose that a minimal glucose-centric model does not accurately describe the physiological behavior of the insulin system and propose a new paradigm focusing on the effects of incretins, arguing that under fasting conditions, insulin is regulated by an adipoincretin effect.
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| 2. |
- Zhang, C., et al.
(författare)
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The acute effect of metabolic cofactor supplementation: a potential therapeutic strategy against non-alcoholic fatty liver disease
- 2020
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Ingår i: Molecular Systems Biology. - : EMBO. - 1744-4292. ; 16:4
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of non-alcoholic fatty liver disease (NAFLD) continues to increase dramatically, and there is no approved medication for its treatment. Recently, we predicted the underlying molecular mechanisms involved in the progression of NAFLD using network analysis and identified metabolic cofactors that might be beneficial as supplements to decrease human liver fat. Here, we first assessed the tolerability of the combined metabolic cofactors including l-serine, N-acetyl-l-cysteine (NAC), nicotinamide riboside (NR), and l-carnitine by performing a 7-day rat toxicology study. Second, we performed a human calibration study by supplementing combined metabolic cofactors and a control study to study the kinetics of these metabolites in the plasma of healthy subjects with and without supplementation. We measured clinical parameters and observed no immediate side effects. Next, we generated plasma metabolomics and inflammatory protein markers data to reveal the acute changes associated with the supplementation of the metabolic cofactors. We also integrated metabolomics data using personalized genome-scale metabolic modeling and observed that such supplementation significantly affects the global human lipid, amino acid, and antioxidant metabolism. Finally, we predicted blood concentrations of these compounds during daily long-term supplementation by generating an ordinary differential equation model and liver concentrations of serine by generating a pharmacokinetic model and finally adjusted the doses of individual metabolic cofactors for future human clinical trials.
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| 3. |
- Lundberg, Jenny, 1976-, et al.
(författare)
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Early Signs of Diabetes Explored from an Engineering Perspective
- 2019
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Ingår i: Smart Industry & Smart Education. - Cham : Springer. - 9783319956787 - 9783319956770 ; , s. 22-31
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Konferensbidrag (refereegranskat)abstract
- Undetected diabetes is a global issue, estimated to over 200 million persons affected. Engineering opportunities in capturing early signs of diabetes has a potential due to the complexity to interpret early signs and link it to diabetes. Persons with untreated diabetes are doubled in risk of getting cardiovascular diseases and may also suffer other consequent diseases. In Sweden, approximately 450 thousand have diabetes where 80-90% are of type 2 with 1/4 unaware of it, i.e. approx. 100 thousand. Screening approaches, searching specifically for diabetes in persons not showing symptoms has been initiated with positive results. However, some general drawbacks of screening such as false sense of security are an issue. In this publication, we focus upon in home measurements and empowering of the individual in identifying early signs of diabetes. The methods in this publication are to gather data, evaluate and give suggestion if clinical test to confirm or reject diabetes. In home measurements, education process with companies for innovation possibilities.
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| 4. |
- Robinson, Jonathan, 1986, et al.
(författare)
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An atlas of human metabolism
- 2020
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Ingår i: Science Signaling. - : American Association for the Advancement of Science (AAAS). - 1945-0877 .- 1937-9145. ; 13:624
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Tidskriftsartikel (refereegranskat)abstract
- Genome-scale metabolic models (GEMs) are valuable tools to study metabolism and provide a scaffold for the integrative analysis of omics data. Researchers have developed increasingly comprehensive human GEMs, but the disconnect among different model sources and versions impedes further progress. We therefore integrated and extensively curated the most recent human metabolic models to construct a consensus GEM, Human1. We demonstrated the versatility of Human1 through the generation and analysis of cell- and tissue-specific models using transcriptomic, proteomic, and kinetic data. We also present an accompanying web portal, Metabolic Atlas (https://www.metabolicatlas.org/), which facilitates further exploration and visualization of Human1 content. Human1 was created using a version-controlled, open-source model development framework to enable community-driven curation and refinement. This framework allows Human1 to be an evolving shared resource for future studies of human health and disease.
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| 5. |
- Georgsson, Mattias, 1969-, et al.
(författare)
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Employing a user-centered cognitive walkthrough to evaluate a mHealth diabetes self-management application : A case study and beginning method validation
- 2019
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Ingår i: Journal of Biomedical Informatics. - : Elsevier. - 1532-0464 .- 1532-0480. ; 91
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Self-management of chronic diseases using mobile health (mHealth) systems and applications is becoming common. Current evaluation methods such as formal usability testing can be very costly and time-consuming; others may be more efficient but lack a user focus. We propose an enhanced cognitive walkthrough (CW) method, the user-centered CW (UC-CW), to address identified deficiencies in the original technique and perform a beginning validation with think aloud protocol (TA) to assess its effectiveness, efficiency and user acceptance in a case study with diabetes patient users on a mHealth self-management application. Materials and methods: A total of 12 diabetes patients at University of Utah Health, USA, were divided into UC-CW and think aloud (TA) groups. The UC-CW method included: making the user the main evaluator for detecting usability problems, having a dual domain facilitator, and using three other improved processes: validated task development, higher level tasks and a streamlined evaluation process. Users interacted with the same mHealth application for both methods. Post-evaluation assessments included the NASA RTLX instrument and a set of brief interview questions. Results: Participants had similar demographic characteristics. A total of 26 usability problems were identified with the UC-CW and 20 with TA. Both methods produced similar ratings: severity across all views (UC-CW = 2.7 and TA = 2.6), numbers of problems in the same views (Main View [UC-CW = 11, TA = 10], Carbohydrate Entry View [UC-CW = 4, TA = 3] and List View [UC-CW = 3, TA = 3]) with similar heuristic violations (Match Between the System and Real World [UC-CW = 19, TA = 16], Consistency and Standards [UC-CW = 17, TA = 15], and Recognition Rather than Recall [UC-CW = 13, TA = 10]). Both methods converged on eight usability problems, but the UC-CW group detected five critical issues while the TA group identified two. The UC-CW group identified needed personalized features for patients’ disease needs not identified with TA. UC-CW was more efficient on average time per identified usability problem and on the total evaluation process with patients. NASA RTLX scores indicated that participants experienced the UC-CW half as cognitively demanding. Common themes from interviews indicated the UC-CW as enjoyable and easy to perform while TA was considered somewhat awkward and more cognitively challenging. Conclusions: UC-CW was effective for finding severe, recurring usability problems and it highlighted the need for personalized user features. The method was also efficient and had high user acceptance. These results indicate UC-CW's utility and user acceptance in evaluating a mHealth self-management application. It provides an additional usability evaluation technique for researchers. © 2019
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| 6. |
- Sayin, Sama I., et al.
(författare)
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Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist.
- 2013
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Ingår i: Cell metabolism. - : Elsevier BV. - 1932-7420 .- 1550-4131. ; 17:2, s. 225-35
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Tidskriftsartikel (refereegranskat)abstract
- Bile acids are synthesized from cholesterol in the liver and further metabolized by the gut microbiota into secondary bile acids. Bile acid synthesis is under negative feedback control through activation of the nuclear receptor farnesoid X receptor (FXR) in the ileum and liver. Here we profiled the bile acid composition throughout the enterohepatic system in germ-free (GF) and conventionally raised (CONV-R) mice. We confirmed a dramatic reduction in muricholic acid, but not cholic acid, levels in CONV-R mice. Rederivation of Fxr-deficient mice as GF demonstrated that the gut microbiota regulated expression of fibroblast growth factor 15 in the ileum and cholesterol 7α-hydroxylase (CYP7A1) in the liver by FXR-dependent mechanisms. Importantly, we identified tauro-conjugated beta- and alpha-muricholic acids as FXR antagonists. These studies suggest that the gut microbiota not only regulates secondary bile acid metabolism but also inhibits bile acid synthesis in the liver by alleviating FXR inhibition in the ileum.
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| 7. |
- Linden, Karolina, 1982, et al.
(författare)
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Well-Being and Diabetes Management in Early Pregnant Women with Type 1 Diabetes Mellitus
- 2016
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Ingår i: International Journal of Environmental Research and Public Health. - Basel, Switzerland : MDPI AG. - 1660-4601 .- 1661-7827. ; 13:8
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Tidskriftsartikel (refereegranskat)abstract
- This paper explores well-being and diabetes management in women with type 1 diabetes mellitus (DM) in early pregnancy and investigates associations among perceived well-being, diabetes management, and maternal characteristics. Questionnaires were answered by 168 Swedish women. Correlation analyses were conducted with Spearman's correlation coefficient (r(s)). The women reported relatively high scores of self-efficacy in diabetes management (SWE-DES-10: 3.91 (0.51)) and self-perceived health (excellent (6.5%), very good (42.3%), good (38.7%), fair (11.3%) and poor (1.2%)). Moderate scores were reported for general well-being (WBQ-12: 22.6 (5.7)) and sense of coherence (SOC-13: 68.9 (9.7), moderate/low scores for hypoglycemia fear (SWE-HFS 26.6 (11.8)) and low scores of diabetes-distress (SWE-PAID-20 27.1 (15.9)). A higher capability of self-efficacy in diabetes management showed positive correlations with self-perceived health (r(s) = 0.41, p < 0.0001) and well-being (r(s) = 0.34, p < 0.0001) as well as negative correlations with diabetes distress (r(s) = 0.51, p < 0.0001) and hypoglycemia worries (r(s) = 0.27, p = 0.0009). Women with HbA1c levels of <= 48 mmL/mol scored higher in the subscales "goal achievement" in SWE-DES (p = 0.0028) and "comprehensibility" in SOC (p = 0.016). Well-being and diabetes management could be supported by strengthening the women's capability to achieve glycemic goals and their comprehensibility in relation to the treatment. Further studies are needed to test this.
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| 8. |
- Kjellqvist, Sanela, et al.
(författare)
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Identification of Shared and Unique Serum Lipid Profiles in Diabetes Mellitus and Myocardial Infarction
- 2016
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 5:12
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Tidskriftsartikel (refereegranskat)abstract
- Background-Diabetes mellitus (DM) and cardiovascular disease are associated with dyslipidemia, but the detailed lipid molecular pattern in both diseases remains unknown. Methods and Results-We used shotgun mass spectrometry to determine serum levels of 255 molecular lipids in 316 controls, 171 DM, and 99 myocardial infarction (MI) events from a cohort derived from the Malmo Diet and Cancer study. Orthogonal projections to latent structures analyses were conducted between the lipids and clinical parameters describing DM or MI. Fatty acid desaturases (FADS) and elongation of very long chain fatty acid protein 5 (ELOVL5) activities were estimated by calculating product to precursor ratios of polyunsaturated fatty acids in complex lipids. FADS genotypes encoding these desaturases were then tested for association with lipid levels and ratios. Differences in the levels of lipids belonging to the phosphatidylcholine and triacylglyceride (TAG) classes contributed the most to separating DM from controls. TAGs also played a dominating role in discriminating MI from controls. Levels of C18:2 fatty acids in complex lipids were lower both in DM and MI versus controls (DM, P=0.004; MI, P=6.0E-06) at least due to an acceleration in the metabolic flux from C18: 2 to C20:4 (eg, increased estimated ELOVL5: DM, P=0.02; MI, P=0.04, and combined elongase-desaturase activities: DM, P=3.0E-06; MI, P=2.0E-06). Minor allele carriers of FADS genotypes were associated with increased levels of C18: 2 (P <= 0.007) and lower desaturase activity (P <= 0.002). Conclusions-We demonstrate a possible relationship between decreased levels of C18: 2 in complex lipids and DM or MI. We thereby highlight the importance of molecular lipids in the pathogenesis of both diseases.
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| 9. |
- Mardinoglu, Adil, 1982, et al.
(författare)
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An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans
- 2018
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 27:3
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Tidskriftsartikel (refereegranskat)abstract
- A carbohydrate-restricted diet is a widely recommended intervention for non-alcoholic fatty liver disease (NAFLD), but a systematic perspective on the multiple benefits of this diet is lacking. Here, we performed a short-term intervention with an isocaloric low-carbohydrate diet with increased protein content in obese subjects with NAFLD and characterized the resulting alterations in metabolism and the gut microbiota using a multi-omics approach. We observed rapid and dramatic reductions of liver fat and other cardiometabolic risk factors paralleled by (1) marked decreases in hepatic de novo lipogenesis; (2) large increases in serum beta-hydroxybutyrate concentrations, reflecting increased mitochondrial beta-oxidation; and (3) rapid increases in folate-producing Streptococcus and serum folate concentrations. Liver transcriptomic analysis on biopsy samples from a second cohort revealed downregulation of the fatty acid synthesis pathway and upregulation of folate-mediated one-carbon metabolism and fatty acid oxidation pathways. Our results highlight the potential of exploring diet-microbiota interactions for treating NAFLD.
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| 10. |
- Lovric, Alen, et al.
(författare)
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Characterization of different fat depots in NAFLD using inflammation-associated proteome, lipidome and metabolome
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Non-alcoholic fatty liver disease (NAFLD) is recognized as a liver manifestation of metabolic syndrome, accompanied with excessive fat accumulation in the liver and other vital organs. Ectopic fat accumulation was previously associated with negative effects at the systemic and local level in the human body. Thus, we aimed to identify and assess the predictive capability of novel potential metabolic biomarkers for ectopic fat depots in non-diabetic men with NAFLD, using the inflammation-associated proteome, lipidome and metabolome. Myocardial and hepatic triglycerides were measured with magnetic spectroscopy while function of left ventricle, pericardial and epicardial fat, subcutaneous and visceral adipose tissue were measured with magnetic resonance imaging. Measured ectopic fat depots were profiled and predicted using a Random Forest algorithm, and by estimating the Area Under the Receiver Operating Characteristic curves. We have identified distinct metabolic signatures of fat depots in the liver (TAG50:1, glutamate, diSM18:0 and CE20:3), pericardium (N-palmitoyl-sphinganine, HGF, diSM18:0, glutamate, and TNFSF14), epicardium (sphingomyelin, CE20:3, PC38:3 and TNFSF14), and myocardium (CE20:3, LAPTGF-beta 1, glutamate and glucose). Our analyses highlighted non-invasive biomarkers that accurately predict ectopic fat depots, and reflect their distinct metabolic signatures in subjects with NAFLD.
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