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- Ahmed, Fozia, et al.
(författare)
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The effects of bisphenol A and bisphenol S on adipokine expression and glucose metabolism in human adipose tissue
- 2020
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Ingår i: Toxicology. - : Elsevier BV. - 0300-483X .- 1879-3185. ; 445
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Tidskriftsartikel (refereegranskat)abstract
- PurposeThe environmental endocrine disruptors, bisphenol A (BPA) and bisphenol S (BPS) are associated with the development of type 2 diabetes. We aim to study the effects of BPA or BPS exposure on adipokine expression in human adipose tissue and on adipocyte glucose uptake.MethodsHuman subcutaneous adipose tissue was treated for 24 or 72 h with environmentally-relevant and supraphysiological concentrations of BPA or BPS (1–104 nM). Following exposure, gene expression of proinflammatory cytokines, adipokines, and estrogen receptors was measured in adipose tissue. Glucose uptake and the insulin signalling pathway were analyzed in isolated adipocytes following adipose tissue culture with BPA for 24 h.ResultsAdipose tissue treated with BPA for 24 h had reduced expression of the proinflammatory genes (IL6, IL1B, TNFA) and adipokines (ADIPOQ, FABP4). BPA and BPS had no effect on the expression of other proinflammatory genes (IL33), adipokines (LEP), or receptors (ESR1, ESR2) after 72-h exposure. Adipose tissue treated with environmentally-relevant concentrations of BPA for 24 h had reduced insulin-stimulated glucose uptake, without altered gene and protein levels of key insulin signalling pathway markers.ConclusionsWe found that human adipose tissue treated with environmentally-relevant concentrations of BPA for 24 h, but not BPS, reduced expression of proinflammatory genes and adipokines. Furthermore, BPA reduced glucose uptake in adipocytes independently of insulin signalling. Such mechanisms can contribute to the development of insulin resistance associated with BPA exposure.
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| 2. |
- Almby, Kristina E., et al.
(författare)
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Time course of metabolic, neuroendocrine, and adipose effects during 2 years of follow-up after gastric bypass in patients with type 2 diabetes
- 2021
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 106:10, s. E4049-E4061
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Tidskriftsartikel (refereegranskat)abstract
- Context: Roux-en-Y gastric bypass surgery (RYGB) markedly improves glycemia in patients with type 2 diabetes (T2D), but underlying mechanisms and changes over time are incompletely understood.Objective: Integrated assessment of neuroendocrine and metabolic changes over time inT2D patients undergoing RYGB.Design and Setting: Follow-up of single-center randomized study.Patients: Thirteen patients with obesity andT2D compared to 22 healthy subjects.Interventions: Blood chemistry, adipose biopsies, and heart rate variability were obtained before and 4, 24, and 104 weeks post-RYGB.Results: After RYGB, glucose-lowering drugs were discontinued and hemoglobin A1c fell from mean 55 to 41 mmol/mol by 104 weeks (P < 0.001). At 4 weeks, morning cortisol (P < 0.05) and adrenocorticotropin (P = 0.09) were reduced by 20%. Parasympathetic nerve activity (heart rate variability derived) increased at 4 weeks (P < 0.05) and peaked at 24 weeks (P < 0.01). C-reactive protein (CRP) and white blood cells were rapidly reduced (P < 0.01). At 104 weeks, basal and insulin-stimulated adipocyte glucose uptake increased by 3-fold vs baseline and expression of genes involved in glucose transport, fatty acid oxidation, and adipogenesis was upregulated (P < 0.01). Adipocyte volume was reduced by 4 weeks and more markedly at 104 weeks, by about 40% vs baseline (P < 0.01).Conclusions: We propose this order of events: (1) rapid glucose lowering (days); (2) attenuated cortisol axis activity and inflammation and increased parasympathetic tone (weeks); and (3) body fat and weight loss, increased adipose glucose uptake, and whole-body insulin sensitivity (months-years; similar to healthy controls).Thus, neuroendocrine pathways can partly mediate early glycemic improvement after RYGB, and adipose factors may promote long-term insulin sensitivity and normoglycemia.
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| 3. |
- Boersma, Greta J., et al.
(författare)
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Altered Glucose Uptake in Muscle, Visceral Adipose Tissue, and Brain Predict Whole-Body Insulin Resistance and may Contribute to the Development of Type 2 Diabetes: A Combined PET/MR Study
- 2018
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Ingår i: Hormone and Metabolic Research. - : Georg Thieme Verlag KG. - 0018-5043 .- 1439-4286. ; 50:8
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Tidskriftsartikel (refereegranskat)abstract
- We assessed glucose uptake in different tissues in type 2 diabetes (T2D), prediabetes, and control subjects to elucidate its impact in the development of whole-body insulin resistance and T2D. Thirteen T2D, 12 prediabetes, and 10 control subjects, matched for age and BMI, underwent OGTT and abdominal subcutaneous adipose tissue (SAT) biopsies. Integrated whole-body 18F-FDG PET and MRI were performed during a hyperinsulinemic euglycemic clamp to asses glucose uptake rate (MRglu) in several tissues. MRglu in skeletal muscle, SAT, visceral adipose tissue (VAT), and liver was significantly reduced in T2D subjects and correlated positively with M-values (r = 0.884, r = 0.574, r = 0.707 and r = 0.403, respectively). Brain MRglu was significantly higher in T2D and prediabetes subjects and had a significant inverse correlation with M-values (r = -0.616). Myocardial MRglu did not differ between groups and did not correlate with the M-values. A multivariate model including skeletal muscle, brain and VAT MRglu best predicted the M-values (adjusted r2 = 0.85). In addition, SAT MRglu correlated with SAT glucose uptake ex vivo (r = 0.491). In different stages of the development of T2D, glucose uptake during hyperinsulinemia is elevated in the brain in parallel with an impairment in peripheral organs. Impaired glucose uptake in skeletal muscle and VAT together with elevated glucose uptake in brain were independently associated with whole-body insulin resistance, and these tissue-specific alterations may contribute to T2D development.
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| 7. |
- Eriksson, Jan W, et al.
(författare)
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Tissue-specific glucose partitioning and fat content in prediabetes and type 2 diabetes: whole-body PET/MRI during hyperinsulinemia
- 2021
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Ingår i: European journal of endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 184:6, s. 879-899
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To obtain direct quantifications of glucose turnover, volumes an d fat content of several tissues in the development of type 2 diabetes (T2D) using a novel integrated a pproach for whole-body imaging. Design and methods: Hyperinsulinemic-euglycemic clamps and simultaneous whole-body integrated [18F]FDG-PET/MRI with automated analyses were performed in control (n = 12), prediabetes (n = 16) and T2D (n = 13) subjects matched for age, sex and BMI. Results: Whole-body glucose uptake (Rd) was reduced by approximately 25% in T2D vs control subjects, and partitioning to brain was increased from 3.8% of total Rd in co ntrols to 7.1% in T2D. In liver, subcutaneous AT, thigh muscle, total tissue glucose metabolic rates (MRglu) and their % of total Rd were reduced in T2D compared to contr ol subjects. The prediabetes group had intermediate findings. Total MRglu in heart, visceral AT, gluteus and calf muscle was similar across groups. Whole-body insulin sensitivity asses sed as glucose infusion rate correlated with liver MR glu but inversely with brain MRglu. Liver fat content correlated with MRglu in brain but inversely with MRglu in other tissues. Calf muscle fat was inversely associated with MR glu only in the same muscle group. Conclusions: This integrated imaging approach provides detailed quantification of tissue-specific glucose metabolism. During T2D development, insulin-stimulated glucose disposal is impaired and increasingly shifted away from muscle, liver and fat toward the brain. Altered glucose handling in the brain and liver fat accumulation may aggravate insulin resistance in several organs. © 2021 BioScientifica Ltd.. All rights reserved.
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| 8. |
- Fanni, Giovanni, et al.
(författare)
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Response of multiple hormones to glucose and arginine challenge in T2DM after gastric bypass
- 2022
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Ingår i: Endocrine Connections. - : Bioscientifica. - 2049-3614. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: In patients with type 2 diabetes mellitus (T2DM), Roux-en-Y gastric bypass (RYGB) leads to beneficial metabolic adaptations, including enhanced incretin secretion, beta-cell function, and systemic insulin sensitivity. We explored the impact of RYGB on pituitary, pancreatic, gut hormones, and cortisol responses to parenteral and enteral nutrient stimulation in patients with obesity and T2DM with repeated sampling up to 2 years after intervention.Methods: We performed exploratory post hoc analyses in a previously reported randomized trial. Levels of adrenocorticotropic hormone (ACTH), cortisol, growth hormone (GH), glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), peptide YY (PYY), ACTH, insulin, and glucagon were measured in 13 patients with T2DM and obesity at four different visits: before and 4, 24, and 104 weeks after RYGB; and in three sequential conditions on the same day: fasting, intravenous arginine challenge, and OGTT.Results: RYGB surprisingly induced a rise in ACTH, cortisol, and GH levels upon an oral glucose load, together with enhanced GLP-1 and PYY responses. Fasting and postarginine GH levels were higher after RYGB, whereas insulin, glucagon, GLP-1, GIP, and cortisol were lower. These endocrine adaptations were seen as early as 4 weeks after surgery and were maintained for up to 2 years.Conclusion: These findings indicate adaptations of glucose sensing mechanisms and responses in multiple endocrine organs after RYGB, involving the gut, pancreatic islets, the pituitary gland, the adrenals, and the brain.
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| 9. |
- Katsogiannos, Petros, 1979-
(författare)
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Bariatric surgery as treatment of type 2 diabetes – clinical and mechanistic aspects
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bariatric surgery can rapidly improve glycemic control and cardiovascular risk factors in patients with T2D and obesity. These improvements appear to be partly independent of weight loss, however, the underlying mechanisms remain incompletely understood. A randomized controlled trial was designed where 19 patients with obesity and T2D were either operated with a Roux-en-Y gastric bypass (RYGB) operation or continued with standard-of-care treatment and followed up for 2 years, providing the data for Paper I-III.In paper I, we focused on changes in whole-body glucose metabolism in relation to changes in adipose tissue metabolism and morphology. We observed an early adipose tissue remodeling and a reduction in adipocyte size that however, did not correlate to the early improvements in metabolic control.In paper II, we analyzed the neuroendocrine changes after RYGB. We observed changes within 4 weeks with signs of enhanced parasympathetic outlow, reduced morning cortisol, and enhanced incretin and glucagon responses to glucose, suggesting that neurohormonal mechanisms can contribute to the rapid improvement of insulin resistance and glycemia following RYGB in T2D.In paper III the patients from the RYGB group were interviewed 2 years after surgery to examine the effects of surgery on health-related quality of life (HRQoL). We found that the improved HRQoL after RYGB was not explained specifically by the magnitude of weight loss, but rather by the participants achieving a state of union between body and consciousness.In paper IV, we compared changes in circulating cytokine and adipokine levels in obese patients with- and without T2D. We observed that the cytokine profile of these patients is altered when compared to lean healthy control subjects and persist to a large extent after RYGB despite the weight loss and improved metabolic status.In conclusion, we observed that in the early post-operative period, neurohormonal changes appear to be more important than adipose tissue changes in improving insulin sensitivity and leading to diabetes remission.In the qualitative part of our study, we observed that the improved HRQoL was not solely explained by weight loss
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| 10. |
- Katsogiannos, Petros, 1979-, et al.
(författare)
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Changes in Circulating Cytokines and Adipokines After RYGB in Patients with and without Type 2 Diabetes
- 2021
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Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 29:3, s. 535-542
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveThis study aimed to compare cytokine and adipokine levels in patients with obesity with and without type 2 diabetes (T2D) at baseline and 6 months after Roux‐en‐Y gastric bypass (RYGB) with healthy controls.MethodsA total of 34 patients (21 with T2D) with BMI of 30 to 45 kg/m2 were compared with 25 healthy controls without obesity. Cytokines, adipokines, and peptides of relevance for inflammation and metabolism were analyzed in plasma.ResultsSignificant decreases in weight and glycated hemoglobin A1c were observed. At baseline, interleukin‐6 (IL‐6), IFN‐β, IL‐18, leptin, and hepatocyte growth factor were higher in all patients with obesity compared with healthy controls. In patients without T2D, TNF‐α, IL‐1α, IL‐2, IL‐15, and visfatin were also increased, whereas bone morphogenic protein‐4 was decreased. Following RYGB, IL‐6 and hepatocyte growth factor were still increased in both groups compared with controls. In T2D patients, IFN‐β, IL‐27, IL‐1α, IL‐2, regenerating islet‐derived protein 3A, visfatin, and osteopontin were found to be increased. In patients without T2D, TNF‐α, IL‐1α, IL‐2, IL‐15, leptin, and visfatin remained increased.ConclusionsThe altered cytokine profile of patients with obesity persisted after RYGB despite large weight loss and improved metabolic status, thus reflecting an inherent inflammatory state.
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