Microdialysis and proteomics of subcutaneous interstitial fluid reveals increased galectin-1 in type 2 diabetes patients

Fryk, Emanuel; Sundelin, Jeanna Perman; Strindberg, Lena; Pereira, Maria J.; Federici, Massimo; Nyström, Fredrik; Schmelz, Martin; Svensson, Per‐Arne; Eriksson, Jan W.; Borén, Jan; Jansson, Per‐Anders

doi:10.1016/j.metabol.2016.04.003

Cited by 27 publications

(26 citation statements)

References 42 publications

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“…Another possible reason is the lower incidence of CIN than renal function decline in our study sample. Furthermore, galectin-1 and diabetes were correlated in this study and in previous reports 17,18 . Before adjustment for diabetes, tertile 3 of the galectin-1 level correlated with CIN.…”

Section: Discussionsupporting

confidence: 88%

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Increased circulating galectin-1 levels are associated with the progression of kidney function decline in patients undergoing coronary angiography

Kuo

Chou

et al. 2020

Sci Rep

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Galectin-1 modulates acute and chronic inflammation, and is associated with glucose homeostasis and chronic renal disease. Whether the serum galectin-1 level can predict short-term and longterm renal outcomes after contrast exposure in patients undergoing coronary angiography (CAG) remains uncertain. This study aimed to evaluate the relationship between the serum galectin-1 level and the incidence of contrast-induced nephropathy (CIN), and to investigate the predictive role of the circulating galectin-1 level for renal function decline in patients undergoing CAG. In total, 798 patients who had undergone CAG were enrolled. Baseline creatinine and serum galectin-1 levels were determined before CAG. CIN was defined as an increase in the serum creatinine level of 0.5 mg/dl or a 25% increase from baseline within 48 h after the procedure, and renal function decline was defined as > 30% reduction of the estimated glomerular filtration rate from baseline. All patients were followed for at least 1 year or until the occurrence of death after CAG. Overall, CIN occurred in 41 (5.1%) patients. During a median follow-up period of 1.4 ± 1.1 years, 80 (10.0%) cases showed subsequent renal function decline. After adjustment for demographic characteristics, kidney function, traditional risk factors, and medications, higher galectin-1 levels were found to be associated independently with a greater risk of renal function decline [tertile 2: hazard ratio (HR) 5.56, 95% confidence interval (CI) 1.79-17.22; tertile 3: HR 5.56, 95% CI 1.97-16.32], but not with CIN, regardless of the presence of diabetes. In conclusion, higher baseline serum galectin-1 levels were associated with a greater risk of renal function decline in patients undergoing CAG, but were not associated independently with CIN. Chronic kidney disease (CKD) is a serious public health problem, and its incidence and prevalence are increasing 1. The early detection of individuals at risk of CKD development or progression is especially important, as early-stage CKD is prevalent and contributes greatly to cardiovascular disease. Research clearly indicates that patients with coronary artery disease (CAD) are at increased risk of progressive renal dysfunction 2. These patients may be further exposed to the risk of contrast-induced nephropathy (CIN), which has an incidence rate of 4.4-22.1%, if they undergo coronary angiography (CAG) 3. CIN has traditionally been considered to be a benign and reversible disease, but it may prolong hospital stays and increase in-hospital mortality 4. Accumulating evidence suggests that CIN is related to long-term renal function decline, in addition to short-term outcomes 5,6. Efforts to predict the occurrence of CIN include the development of risk scoring systems composed of baseline risk factors 7 , renal

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Section: Discussionsupporting

confidence: 88%

“…Diabetes is a traditional risk factor for CIN 7 and CKD 17 . Recent evidence indicates that galectin-1 levels are increased in the proteome in subcutaneous interstitial fluid 18 and plasma 19 in patients with type 2 diabetes. The galectin-1 level is also elevated in the glomerular proteome in mice with CKD 20 .…”

mentioning

confidence: 99%

Increased circulating galectin-1 levels are associated with the progression of kidney function decline in patients undergoing coronary angiography

Kuo

Chou

et al. 2020

Sci Rep

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“…Recent studies have shown that galectin expression is upregulated in adipose tissue of mice with high-fat-diet-induced obesity [ 2 ] and that serum galectin-1 levels is positively correlated with body fat in children with obesity [ 3 ]. Moreover, we have showed that galectin-1 gene expression in adipose tissue decreased during weight loss in obese patients and increased after overfeeding in healthy subjects [ 4 ]. In line, a study in overweight and obese participants showed that galectin-1 expression in abdominal adipose tissue is regulated by dietary interventions [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Galectin-1 is inversely associated with type 2 diabetes independently of obesity – A SCAPIS pilot study

et al. 2019

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Objectives Galectin-1 is a recently discovered adipokine that increases with obesity and increased energy intake in adipose tissue. Our aim was to assess whether serum galectin-1 is associated with type 2 diabetes (T2D) and other parameters of the metabolic syndrome independently of body mass index (BMI) in a cohort from the general population. Methods In this cross-sectional population-based cohort study from the western part of Sweden, we investigated associations between serum galectin-1, clinical characteristics and inflammatory markers in 989 women and men aged 50–65 years [part of the Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot cohort]. Results We showed in linear models that serum galectin-1 was independently and: (1) inversely associated with T2D (p < 0.05) and glucose (p < 0.05); and (2) positively associated with age (p < 0.01), sex (p < 0.01), BMI (p < 0.01), insulin (p < 0.01) and C-reactive protein (p < 0.01). Furthermore, galectin-1 demonstrated univariate correlations with triglycerides (r = 0.20, p < 0.01), homeostasis model assessment for insulin resistance (r = 0.24, p < 0.01), tumor necrosis factor-α (r = 0.24, p < 0.01), interleukin-6 (IL-6; r = 0.20, p < 0.01) and HbA1c (r = 0.14, p < 0.01). Conclusion In a cross-sectional study of a middle-aged population, we showed that serum galectin-1 is: (1) inversely associated with T2D independently of BMI; and (2) independently associated with other markers of the metabolic syndrome These results warrant prospective and functional studies on the role of galectin-1 in T2D.

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“…In addition, treatment of the cells with TGF-b1 induced differentiation of fibroblasts to myofibroblasts in NIH3T3 and IMR-90 cells (25). Recent study (26) showed with a proteomics approach that Gal-1 is increased in subcutaneous dialysates from type 2 diabetes compared with those from healthy individuals. These proteomics data showed 36 proteins, including Gal-1, were significantly increased in interstitial fluid of subcutaneous adipose tissues of patients with type 2 diabetes compared with those of healthy subjects (26).…”

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confidence: 99%

Galectin‐1 is a new fibrosis protein in type 1 and type 2 diabetes

Al-Obaidi¹,

Mohan

Liang³

et al. 2018

The FASEB Journal

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Chronic exposure of tubular renal cells to high glucose contributes to tubulointerstitial changes in diabetic nephropathy. In the present study, we identified a new fibrosis gene called galectin-1 (Gal-1), which is highly expressed in tubular cells of kidneys of type 1 and type 2 diabetic mouse models. Gal-1 protein and mRNA expression showed significant increase in kidney cortex of heterozygous Akita and db/db mice compared with wild-type mice. Mouse proximal tubular cells exposed to high glucose showed significant increase in phosphorylation of Akt and Gal-1. We cloned Gal-1 promoter and identified the transcription factor AP4 as binding to the Gal-1 promoter to up-regulate its function. Transfection of cells with plasmid carrying mutations in the binding sites of AP4 to Gal-1 promoter resulted in decreased protein function of Gal-1. In addition, inhibition of Gal-1 by OTX-008 showed significant decrease in p-Akt/AP4 and protein-promoter activity of Gal-1 and fibronectin. Moreover, down-regulation of AP4 by small interfering RNA resulted in a significant decrease in protein expression and promoter activity of Gal-1. We found that kidney of Gal-1 mice express very low levels of fibronectin protein. In summary, Gal-1 is highly expressed in kidneys of type 1 and 2 diabetic mice, and AP4 is a major transcription factor that activates Gal-1 under hyperglycemia. Inhibition of Gal-1 by OTX-008 blocks activation of Akt and prevents accumulation of Gal-1, suggesting a novel role of Gal-1 inhibitor as a possible therapeutic target to treat renal fibrosis in diabetes.-Al-Obaidi, N., Mohan, S., Liang, S., Zhao, Z., Nayak, B. K., Li, B., Sriramarao, P., Habib, S. L. Galectin-1 is a new fibrosis protein in type 1 and type 2 diabetes.

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Microdialysis and proteomics of subcutaneous interstitial fluid reveals increased galectin-1 in type 2 diabetes patients

Cited by 27 publications

References 42 publications

Increased circulating galectin-1 levels are associated with the progression of kidney function decline in patients undergoing coronary angiography

Increased circulating galectin-1 levels are associated with the progression of kidney function decline in patients undergoing coronary angiography

Galectin-1 is inversely associated with type 2 diabetes independently of obesity – A SCAPIS pilot study

Galectin‐1 is a new fibrosis protein in type 1 and type 2 diabetes

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