scholarly journals Vitamin-D-Binding Protein Contributes to the Maintenance of α Cell Function and Glucagon Secretion

Cell Reports ◽  
2020 ◽  
Vol 31 (11) ◽  
pp. 107761
Author(s):  
Katrina Viloria ◽  
Daniela Nasteska ◽  
Linford J.B. Briant ◽  
Silke Heising ◽  
Dean P. Larner ◽  
...  
2019 ◽  
Author(s):  
Katrina Viloria ◽  
Daniela Nasteska ◽  
Linford J.B. Briant ◽  
Silke Heising ◽  
Dean Larner ◽  
...  

ABSTRACTVitamin D-binding protein (DBP) or GC-globulin carries vitamin D metabolites from the circulation to target tissues. DBP expression is highly-localized to the liver and pancreatic α-cells. While DBP serum levels, gene polymorphisms and autoantigens have all been associated with diabetes risk, the underlying mechanisms remain unknown. Here, we show that DBP regulates α-cell morphology, α-cell function and glucagon secretion. Deletion of DBP led to smaller and hyperplastic α-cells, altered Na+ channel conductance, impaired α-cell activation by low glucose, and reduced rates of glucagon secretion. Mechanistically, this involved reversible changes in islet microfilament abundance and density, as well as changes in glucagon granule distribution. Defects were also seen in β-cell and δ-cell function. Immunostaining of human pancreata revealed generalized loss of DBP expression as a feature of late-onset and longstanding, but not early-onset type 1 diabetes. Thus, DBP is a critical regulator of α-cell phenotype, with implications for diabetes pathogenesis.HIGHLIGHTSDBP expression is highly-localized to mouse and human α-cellsLoss of DBP increases α-cell number, but decreases α-cell sizeα-cells in DBP knockout islets are dysfunctional and secrete less glucagonDBP expression is decreased in α-cells of donors with late-onset or longstanding type 1 diabetes


2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Nabila A. Abdella ◽  
Olusegun A. Mojiminiyi

Introduction. Studies have shown increased urine excretion of vitamin D-binding protein (VDBP) in patients with diabetic nephropathy (DN) resulting from postulated mechanisms linked to renal tubular damage. In this study, we evaluate the utility of VDBP clearance ratio as a novel determinant of glycemic status, DN, and other diabetes-associated complications.Methods. Levels of vitamin D, HbA1c, serum, urine concentrations of VDBP, and creatinine were measured in 309 subjects. The ratio of urine microalbumin to creatinine was determined to categorize subjects as normoalbuminuric (NAO), microalbuminuric (MIA), and macroalbuminuric (MAA). The VDBP clearance ratio was calculated.Results. Mean VDBP clearance ratios in NAO, MIA, and MAA were 0.7, 4, and 15, respectively. Significant positive correlations of VDBP clearance ratio were found with age, WC, SBP, DBP, TG, glucose, HbA1c, urine VDBP, urine microalbumin, and urine microalbumin/creatinine, and a significant negative correlation was found with the steady-state estimate of beta cell function (B%). Receiver operating curve (ROC) analyses of the use of VDBP clearance ratio for detection of albumin status shows a value of 0.81 for the area under the curve.Conclusions. The strong associations of VDBP clearance ratio with glycemic control and diabetes-associated complications suggest that this index could play a wider role in detection and/or pathogenesis and complications of diabetes.


2019 ◽  
Author(s):  
Ankana Ganguly ◽  
Alexandra Shattock ◽  
Annsha Joseph ◽  
Janesh Gupta ◽  
Martin Hewison

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria Zacharioudaki ◽  
Ippokratis Messaritakis ◽  
Emmanouil Galanakis

AbstractThe role of vitamin D in innate and adaptive immunity is recently under investigation. In this study we explored the potential association of genetic variances in vitamin D pathway and infections in infancy. Τhis prospective case–control study included infants 0–24 months with infection and age-matched controls. The single nucleotide polymorphisms of vitamin D receptor (VDR) gene (BsmI, FokI, ApaI, TaqI), vitamin D binding protein (VDBP) (Gc gene, rs7041, rs4588) and CYP27B1 (rs10877012) were genotyped by polymerase chain reaction-restriction fragment length polymorphism. In total 132 infants were enrolled, of whom 40 with bacterial and 52 with viral infection, and 40 healthy controls. As compared to controls, ΤaqI was more frequent in infants with viral infection compared to controls (p = 0.03, OR 1.96, 95% CI 1.1–3.58). Moreover, Gc1F was more frequent in the control group compared to infants with viral infection (p = 0.007, OR 2.7, 95% CI 1.3–5.6). No significant differences were found regarding the genetic profile for VDR and VDBP in infants with bacterial infection compared to the controls and also regarding CYP27B1 (rs10877012) between the studied groups. Genotypic differences suggest that vitamin D pathway might be associated with the host immune response against viral infections in infancy.


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