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  • The Endocrine Society  (3)
  • 1
    In: Endocrinology, The Endocrine Society, Vol. 152, No. 12 ( 2011-12-01), p. 4601-4609
    Abstract: The aim of this study was to assess the expression of different types of cadherins in human islets and their role in human β-cell apoptosis. Expression of E-, N-, and P-cadherins was studied by immunofluorescence on pancreas sections and islet cells, and by Western blotting on protein extracts of isolated islets and islet cells. The effects of specific cadherins on cell adhesion and apoptosis were studied using chimeric proteins containing functional E-, N-, or P-cadherin ectodomains fused to Fc fragment of Ig (E-cad/Fc, N-cad/Fc, and P-cad/Fc) and immobilized on glass substrate. β-Cells were identified by immunofluorescence for insulin and apoptotic cells by terminal deoxynucleotide transferase-mediated 2′-deoxyuridine, 5′-triphosphate nick-end labeling. By immunofluorescence, we showed that E- and N-, and not P-, cadherins were expressed at the surface of islet cells. By triple staining, we showed that E-cadherin was expressed at similar extent in β- and α-cells, whereas N-cadherin was preferentially expressed in β-cells. These results were confirmed by Western blot analysis using protein extracts from fluorescence-activated cell sorting-sorted β- and non-β-cells. Adhesion tests showed that the affinity of islet cells for E-cad/Fc and N-cad/Fc and not for P-cad/Fc was increased compared with control. By terminal deoxynucleotide transferase-mediated 2′-deoxyuridine, 5′-triphosphate nick-end labeling, we showed that the percentage of apoptotic cells was lower in aggregated β-cells compared with single β-cells and that attachment to E-cad/Fc and N-cad/Fc and not to P-cad/Fc decreased apoptosis of single β-cells compared with control. Our results show that at least E- and N-cadherins are expressed at the surface of human β-cells and that these adhesion molecules are involved in the maintenance of β-cell viability.
    Type of Medium: Online Resource
    ISSN: 0013-7227 , 1945-7170
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2011
    detail.hit.zdb_id: 2011695-0
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  • 2
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 7, No. Supplement_1 ( 2023-10-05)
    Abstract: Disclosure: S. Monnerat: None. J. Refardt: None. C. Meier: None. M. Christ-Crain: None. INTRODUCTION Hyponatremia is the most common electrolyte disorder encountered in clinical practice and is associated with increased mortality and morbidity, including an increased risk for osteoporosis and fragility fractures. Preclinical studies suggest that hyponatremia upregulates osteoclasts. In a previous analysis of 88 hospitalized patients with a syndrome of inappropriate antidiuresis (SIAD), we observed that hyponatremia normalization after 4 days had a positive impact on osteoblast function. METHODS This is a secondary analysis of a double-blind, crossover, placebo-controlled trial investigating the effect of 4-week treatment with empagliflozin 25mg/day as compared to placebo in 14 outpatients with chronic SIAD (NCT03202667). Two patients with an antiresorptive osteoporosis treatment and 1 patient with recent hip arthroplasty were excluded (n=11). The primary objective was to investigate the relationship between the change in bone formation index (BFI), defined as PINP/CTX, and the change in plasma sodium levels. Secondary objectives included the relationship between the change in the osteoblasts markers procollagen type 1 N (P1NP) and osteocalcin and the osteoclasts markers C-telopeptide crosslink (CTX), and the change in plasma sodium levels over the treatment period. Linear mixed models and Spearman correlation were computed. RESULTS Six out of the 11 outpatients with a chronic SIAD were female (median [IQR] age 73 years [66, 78] ). At baseline, median [IQR] CTX concentration was 0.47 ug/L [0.29, 0.65] , median [IQR] osteocalcin was 18.00 ug/L [13.95, 25.87] and median [IQR] P1NP was 64.64 ug/L [45.62, 68.45] . The calculated median BFI [IQR] was 131.86 [96.21, 168.73] . A sodium increase of 1 mmol/L was associated with an increase of 5.21 in BFI (95%-CI: 1.41, 9.00, p = 0.013) and with an increase of 1.48 ug/L in P1NP (95%-CI: 0.26, 2.62, p = 0.03). Plasma sodium concentration was not associated with a change in osteocalcin (β = 0.32; 95%-CI: -0.09, 0.72, p = 0.18), nor with a change in CTX (β = 0.003; 95%-CI: -0.008, 0.014, p = 0.324). Empagliflozin was not a significant predictor for the change of any bone markers and there was no interaction between treatment allocation and sodium. Changes in plasma sodium were positively correlated with changes in BFI and P1NP (BFI: ρ = 0.55, p & lt; 0.001; P1NP: ρ = 0.45, p = 0.004) but not with CTX and osteocalcin (CTX: ρ = -0.21, p = 0.184; Osteocalcin: ρ = 0.34, p = 0.149). CONCLUSION An increase in plasma sodium levels in outpatients with chronic SIAD was associated with an increase in bone formation index (P1NP/CTX), which seemed to be triggered by an increase in P1NP, a surrogate marker of osteoblast function. This supports the importance of treating hyponatremia, particularly in older adults in whom chronic hyponatremia is also associated with falls. Presentation: Sunday, June 18, 2023
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2023
    detail.hit.zdb_id: 2881023-5
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  • 3
    Online Resource
    Online Resource
    The Endocrine Society ; 2023
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 108, No. 10 ( 2023-09-18), p. e1027-e1033
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 108, No. 10 ( 2023-09-18), p. e1027-e1033
    Abstract: Hyponatremia is associated with increased risk for osteoporosis. Preclinical studies in untreated hyponatremia suggest osteoclast upregulation, whereas a clinical study showed improved osteoblast function after hyponatremia normalization in hospitalized patients with syndrome of inappropriate antidiuresis (SIAD). Objective This work aimed to investigate the effect of an increase in sodium on bone turnover, that is, the ratio of the osteoblast marker procollagen type 1 N-terminal propeptide (P1NP) to the osteoclast marker cross-linked C-terminal telopeptide of type 1 collagen (CTX), in outpatients with chronic SIAD. Methods A predefined secondary analysis was conducted of the 2-month double-blind, crossover, placebo-controlled SANDx Trial (NCT03202667) performed from December 2017 to August 2021. Participants included 11 outpatients with chronic SIAD: 6 women, median age 73 years, who received a 4-week treatment with 25-mg empagliflozin or placebo. Main outcome measures included the relationship between the change in bone formation index (BFI), defined as P1NP/CTX, and the change in plasma sodium levels. Results Changes in sodium were positively correlated with changes in BFI and P1NP (BFI: ρ=.55; P & lt; .001; P1NP: ρ=.45; P = .004) but not with CTX (P = .184) and osteocalcin (P = .149). A sodium increase of 1 mmol/l was associated with an increase of 5.21 in BFI (95% CI, 1.41-9.00; P = .013) and with an increase of 1.48 µg/l in P1NP (95% CI, .26-2.62; P = .03). The effect of sodium change on bone markers was independent of the study medication empagliflozin. Conclusion An increase in plasma sodium levels in outpatients with chronic hyponatremia due to SIAD, even when mild, was associated with an increase in bone formation index (P1NP/CTX) triggered by an increase in P1NP, a surrogate marker of osteoblast function.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
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    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2023
    detail.hit.zdb_id: 2026217-6
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