Hofso D.,Morbid Obesity Center |
Birkeland K.I.,University of Oslo |
Holst J.J.,Endocrinology Research Section |
Bollerslev J.,University of Oslo |
And 5 more authors.
Diabetology and Metabolic Syndrome | Year: 2015
Background: Gastric bypass surgery seems to have an effect on glucose metabolism beyond what is mediated through weight reduction. The magnitude of this effect on fasting and post-challenge glucose levels remains unknown. Results: Morbidly obese subjects without known diabetes performed a 75 g oral glucose tolerance test before and after either gastric bypass surgery (n = 64) or an intensive lifestyle intervention programme (n = 55), ClinicalTrials.gov identifier NCT00273104. The age-adjusted effects of the therapeutic procedures and percentage weight change on fasting and 2-h glucose levels at 1 year were explored using multiple linear regression analysis. Mean (SD) serum fasting and 2-h glucose levels at baseline did not differ between the surgery and lifestyle groups. Weight-loss after surgical treatment and lifestyle intervention was 30 (8) and 9 (10) % (p < 0.001). At 1 year, fasting and 2-h glucose levels were significantly lower in the surgery group than in the lifestyle group, 4.7 (0.4) versus 5.4 (0.7) mmol/l and 3.4 (0.8) versus 6.0 (2.4) mmol/l, respectively (both p < 0.001). Gastric bypass and weight-loss had both independent glucose-lowering effects on 2-h glucose levels [B (95 % CI) 1.4 (0.6-2.3) mmol/l and 0.4 (0.1-0.7) mmol/l per 10 % weight-loss, respectively]. Fasting glucose levels were determined by weight change [0.2 (0.1-0.3) mmol/l per 10 % weight-loss] and not by type of treatment. Conclusions: Gastric bypass surgery has a clinically relevant glucose-lowering effect on post-challenge glucose levels which is seemingly not mediated through weight-loss alone. © 2015 Høfso et al. Source
Dahllof M.S.,Endocrinology Research Section |
Christensen D.P.,Endocrinology Research Section |
Lundh M.,Endocrinology Research Section |
Dinarello C.A.,Talfarmaco |
And 6 more authors.
Islets | Year: 2012
Aims: Pro-inflammatory cytokines and chemokines, in particular IL-1β, IFNγ and CXCL10, contribute to β-cell failure and loss in DM via IL-1R, IFNγR and TLR4 signaling. IL-1 signaling deficiency reduces diabetes incidence, islet IL-1β secretion and hyperglycemia in animal models of diabetes. Further, IL-1R antagonism improves normoglycemia and β-cell function in type 2 diabetic patients. Inhibition of lysine deacetylases (KDACi) counteracts β-cell toxicity induced by the combination of IL-1 and IFNγ and reduces diabetes incidence in non-obese diabetic (NOD) mice. We hypothesized that KDACi breaks an autoinflammatory circuit by differentially preventing β-cell expression of the β-cell toxic inflammatory molecules IL-1β and CXCL10 induced by single cytokines. Results: CXCL10 did not induce transcription of IL-1β mRNA. IL-1β induced β-cell IL-1β mRNA and both IL-1β and IFNγ individually induced Cxcl10 mRNA transcription. Givinostat inhibited IL-1β-induced IL-1β mRNA expression in INS-1 and rat islets and IL-1β processing in INS-1 cells. Givinostat also reduced IFNγ induced Cxcl10 transcription in INS-1 cells but not in rat islets, while IL-1β induced Cxcl10 transcription was unaffected in both. Materials and Methods: INS-1 cells and rat islets of Langerhans were exposed to IL-1β, IFNγ or CXCL10 in the presence or absence of KDACi (givinostat). Cytokine and chemokine mRNA expressions were quantified by real-Time qPCR, and IL-1β processing by western blotting of cell lysates. Conclusion/Interpretation: Inhibition of β-cell IL-1β expression and processing and Cxcl10 transcription contributes to the β-cell protective actions of KDACi. In vitro β-cell destructive effects of CXCL10 are not mediated via IL-1β transcription. The differential proinflammatory actions of KDACs may be attractive novel drug targets in DM.©2012 Landes Bioscience. Source