scholarly journals FOXO1 Mediates Vitamin D Deficiency-Induced Insulin Resistance in Skeletal Muscle

2015 ◽  
Vol 31 (3) ◽  
pp. 585-595 ◽  
Author(s):  
Songcang Chen ◽  
S Armando Villalta ◽  
Devendra K Agrawal
2021 ◽  
Vol 22 (12) ◽  
pp. 6444
Author(s):  
Anna Gabryanczyk ◽  
Sylwia Klimczak ◽  
Izabela Szymczak-Pajor ◽  
Agnieszka Śliwińska

There is mounting evidence that type 2 diabetes mellitus (T2DM) is related with increased risk for the development of cancer. Apart from shared common risk factors typical for both diseases, diabetes driven factors including hyperinsulinemia, insulin resistance, hyperglycemia and low grade chronic inflammation are of great importance. Recently, vitamin D deficiency was reported to be associated with the pathogenesis of numerous diseases, including T2DM and cancer. However, little is known whether vitamin D deficiency may be responsible for elevated cancer risk development in T2DM patients. Therefore, the aim of the current review is to identify the molecular mechanisms by which vitamin D deficiency may contribute to cancer development in T2DM patients. Vitamin D via alleviation of insulin resistance, hyperglycemia, oxidative stress and inflammation reduces diabetes driven cancer risk factors. Moreover, vitamin D strengthens the DNA repair process, and regulates apoptosis and autophagy of cancer cells as well as signaling pathways involved in tumorigenesis i.e., tumor growth factor β (TGFβ), insulin-like growth factor (IGF) and Wnt-β-Cathenin. It should also be underlined that many types of cancer cells present alterations in vitamin D metabolism and action as a result of Vitamin D Receptor (VDR) and CYP27B1 expression dysregulation. Although, numerous studies revealed that adequate vitamin D concentration prevents or delays T2DM and cancer development, little is known how the vitamin affects cancer risk among T2DM patients. There is a pressing need for randomized clinical trials to clarify whether vitamin D deficiency may be a factor responsible for increased risk of cancer in T2DM patients, and whether the use of the vitamin by patients with diabetes and cancer may improve cancer prognosis and metabolic control of diabetes.


Author(s):  
Xin Chen ◽  
Chang Chu ◽  
Cornelia Doebis ◽  
Volker von Baehr ◽  
Berthold Hocher

Abstract Background Animal studies suggested that vitamin D might decrease insulin resistance. Estrogen increased insulin sensitivity and glucose tolerance in rodents. However, sex-specific association of vitamin D with insulin resistance in humans remains unclear. Objectives To investigate the sex-dependency of the association of insulin resistance and 25(OH)D in a large Caucasian population. Methods Cross-sectional study from out-patients’ blood samples with measurements of 25(OH)D and HOMA-IR drawn at exactly the same day (N=1887). This cohort was divided into three groups: i) group with vitamin D deficiency (n=1190), ii) group with vitamin D sufficiency (N=686)), iii) vitamin D excess groups (n=11), the vitamin D excess group was excluded from further analysis due to the small size. Results Analysis of the entire study population showed that serum 25-hydroxyvitamin D was inversely associated with HOMA-IR (rs=-0.19, P<0.0001). When considering the vitamin D status, this association was only seen in the vitamin D deficiency group, but not in the vitamin D sufficient group. The correlation was sex-dependent: HOMA-IR was inversely correlated with vitamin D in women with vitamin D deficiency (rs=-0.26, P<0.0001) but not in men with vitamin D deficiency (rs=0.01, P=0.714). After multivariate linear regression analysis considering confounding factors, this relationship was again only seen in women. Conclusion Vitamin D was inversely and independently associated with insulin resistance only in women with vitamin D deficiency. Based on our data, we suggest that in particular vitamin D deficient women might benefit from vitamin D substitution by improving insulin resistance. This, however, needs to be proven in adequately designed double-blind placebo-controlled clinical studies.


2011 ◽  
pp. P3-392-P3-392
Author(s):  
Christian L Roth ◽  
Clinton Elfers ◽  
Susan J Melhorn ◽  
Dianne Lattemann ◽  
Andy Hoofnagle ◽  
...  

2020 ◽  
Vol 13 (1) ◽  
pp. 82
Author(s):  
Aidah Juliaty ◽  
Putri Lestari Gabrilasari ◽  
Dasril Daud ◽  
Johan Setyawan Lisal

INTRODUCTION: Obesity represents the major risk factor for development of insulin resistance during childhood and adolescents. In obesity, adipose tissue release free fatty acids, various hormones, and cytokines, resulting in insulin resistance. This study aimed to establish the correlation between vitamin D deficiency and the incidence of insulin resistance in obese children. DESIGN AND METHOD: This analytical cross-sectional study was arranged from December 2019 - February 2020 included 96 students aged 11 - 17 years old from junior and senior high school who met the criteria for obesity in Makassar. The study subjects were parted into two groups, obese children with vitamin D deficiency (levels of 25-hydroxyvitamin D ≤ 20 ng/ml) and obese children without vitamin D deficiency group (levels of 25-hydroxyvitamin D > 20 ng/ml). Data were analyzed using univariate and bivariate analysis. RESULTS: The frequency of insulin resistance in obese children with vitamin D deficiency was 28 (54.9%), while obese children without vitamin D deficiency was 10 (22.2%). Based on statistical analysis, the frequency of the occurrence of insulin resistance in vitamin D deficiency obese children was higher than in obese children without vitamin D deficiency with OR = 4.261 (95% CI 1.744 – 10.411), p = 0.001. CONCLUSION: The risk of insulin resistance in obese children with vitamin D deficiency is 4.261 times higher than obese children without vitamin D deficiency.


2020 ◽  
Author(s):  
Emma L Watson ◽  
Thomas J Wilkinson ◽  
Tom F O’Sullivan ◽  
Luke A Baker ◽  
Douglas W Gould ◽  
...  

AbstractEvidence is growing for a role of vitamin D in regulating skeletal muscle mass, strength and functional capacity. Given the role the kidneys play in activating total vitamin D, and the high prevalence of vitamin D deficiency in Chronic Kidney Disease (CKD), it is possible that deficiency contributes to the low levels of physical function and muscle mass in these patients. This is a secondary cross-sectional analysis of previously published interventional study, with ex vivo follow up work. 34 CKD patients at stages G3b-5 (eGFR 25.5 ± 8.3ml/min/1.73m2; age 61 ± 12 years) were recruited, with a sub-group (n=20) also donating a muscle biopsy. Vitamin D and associated metabolites were analysed in plasma by liquid chromatography tandem-mass spectroscopy and correlated to a range of physiological tests of muscle size, function, exercise capacity and body composition. The effects of 1α,25(OH)2D3 supplementation on myogenesis and myotube size was investigated in primary skeletal muscle cells from vitamin D deficient donors. In vivo, there was no association between total or active vitamin D and muscle size or strength, but a significant correlation with was seen with the total form. Ex vivo, 1α,25(OH)2D3 supplementation reduced IL-6 mRNA expression, but had no effect upon proliferation, differentiation or myotube diameter. This early preliminary work suggests that vitamin D deficiency is not a prominent factor driving the loss of muscle mass in CKD, but may play a role in reduced exercise capacity.


2011 ◽  
Vol 31 (39) ◽  
pp. 13728-13738 ◽  
Author(s):  
S. E. Tague ◽  
G. L. Clarke ◽  
M. K. Winter ◽  
K. E. McCarson ◽  
D. E. Wright ◽  
...  

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Coc. Lizarraga ◽  
S Lindenberg ◽  
G Juu. Almind ◽  
F Lindenberg

Abstract Study question Is vitamin D deficiency more prevalent in PCOS patients? Is there a link between vitamin D levels and metabolic status in PCOS subjects? Summary answer An inverse relationship between vitamin D levels and metabolic status was demonstrated and it is thought to be responsible of its pathogenesis. What is known already PCOS is a multifactorial condition, characterised by failure in oogenesis and anovulation. Obesity is a common condition linked to its clinical features and studies have reported inverse associations between BMI and severity of the condition. Furthermore, 67–85% of PCOS patients have vitamin D deficiency. Low levels of vitamin D have been found to be closely related to insulin resistance, obesity, or hyperandrogenism and there is a significant association between serum vitamin D levels and reproductive function. Other factors such as AMH have also been described as possibly involved in the pathophysiology. Study design, size, duration We performed a retrospective, analytical and observational study in the Copenhagen Fertility Center. Patients referred with cycle abnormalities, hirsutism, and infertility were evaluated. A total of 778 women were enrolled consecutively from January 2019 to October 2020. Subjects who had major medical disorders were excluded. We selected those in which vitamin D was measured in the baseline analysis selecting a total of 396 patients. The further analysis has been carried out from 100 randomly selected patients. Participants/materials, setting, methods Blood samples were drawn after overnight fasting. They were all assayed in the same laboratory. Biochemical parameters were analyzed using descriptive statistics. Same parameters were studied after dividing into vitamin D deficiency group or optimal levels using a multiple t-test. Correlation between variables was determined. Graphpad Prism program version 8 was used to perform the calculations. The level of statistical significance was set at P-value < 0.05. Main results and the role of chance A total of 100 subjects fulfilling the inclusion criteria were selected randomly from 396 PCOS women. Serum vitamin D concentrations were highly variable ranging from 16 nmol/L to 175 nmol/L. The prevalence of vitamin D deficiency was 24% and 41% of the subjects were classified as vitamin D insufficient. Only 35% of our patients had optimal vitamin D values. We compared data between the group with optimal values of vitamin D (Group A) versus the group with insufficient/deficient vitamin D values (Group B). We found statistical difference between groups in PTH values, being notably higher in group B compared with group A. Despite no statistically significant difference was obtained, it is important to highlight that the mean of SHBG was lower in group B and the mean of androstenedione, AMH, FAI and HOMA-IR were much higher in this group as well. Following the HOMA-IR criteria, 55% of patients had insulin resistance. Specifically, 26% had moderate insulin resistance and 29% severe insulin resistance. Levels of vitamin D were negatively correlated with FAI, AMH and HOMA-IR and positively correlated with HDL-Cholesterol and SHBG. Statistically significant differences were evidenced in the correlation between vitamin D and FAI and SHBG. Limitations, reasons for caution This is a retrospective observational study on a consecutive admitted patient group with a lack of a control group. Another limitation is the small sample size. It is difficult to generalize with other degrees of severity. We didn’t assess seasonal variability or if they were taking any vitamin D supplementation. Wider implications of the findings: Properly randomized clinical trials are mandatory to achieve more conclusive results about the role of vitamin D. Available evidence is promising but not sufficient to draw final conclusions. The aim is to better understand the pathophysiology of the condition and the factors involved and to find new target treatments. Trial registration number 1


2018 ◽  
Vol 15 (4) ◽  
pp. 294-301 ◽  
Author(s):  
Leila Hadjadj ◽  
Szabolcs Várbíró ◽  
Eszter Mária Horváth ◽  
Anna Monori-Kiss ◽  
Éva Pál ◽  
...  

Hyperandrogenic state in females is accompanied with metabolic syndrome, insulin resistance and vascular pathologies. A total of 67%–85% of hyperandrogenic women suffer also from vitamin D deficiency. We aimed to check a potential interplay between hyperandrogenism and vitamin D deficiency in producing insulin resistance and effects on coronary resistance arteries. Adolescent female rats were divided into four groups, 11–12 animals in each. Transdermal testosterone-treated and vehicle-treated animals were kept either on vitamin D-deficient or on vitamin D-supplemented diet for 8 weeks. Plasma sexual steroid, insulin, leptin and vitamin D plasma levels were measured, and oral glucose tolerance test was performed. In coronary arterioles, insulin receptor and vitamin D receptor expressions were tested by immunohistochemistry, and insulin-induced relaxation was measured in vitro on isolated coronary resistance artery segments. Testosterone impaired glucose tolerance, and it diminished insulin relaxation but did not affect the expression of insulin and vitamin D receptors in vascular tissue. Vitamin D deficiency elevated postprandial insulin levels and homeostatic model assessment insulin resistance. It also diminished insulin-induced coronary arteriole relaxation, while it raised the expression of vitamin D and insulin receptors in the endothelial and medial layers. Our conclusion is that both hyperandrogenism and vitamin D deficiency reduce sensitivity of coronary vascular tissue to insulin, but they do it with different mechanisms.


2020 ◽  
Vol 45 (10) ◽  
pp. 1092-1098
Author(s):  
Soodabeh Aliashrafi ◽  
Mehrangiz Ebrahimi-Mameghani ◽  
Mohammad Asghari Jafarabadi ◽  
Lida Lotfi-Dizaji ◽  
Elnaz Vaghef-Mehrabany ◽  
...  

As there is limited and inconsistent evidence in potential role of vitamin D on insulin resistance and matrix metalloproteinases, this study aimed to examine the effect of vitamin D supplementation on glucose homeostasis, insulin resistance, and matrix metalloproteinases in obese subjects with vitamin D deficiency. A total of 44 participants with serum 25-hydroxyvitamin D (25(OH)D) level ≤ 50 nmol/L and body mass index (BMI) 30–40 kg/m2 were randomly allocated into receiving weight reduction diet with either 50 000 IU vitamin D3 pearl (n = 22) or placebo (n = 22) once weekly for 12 weeks. Primary outcomes were changes in fasting serum glucose (FSG), homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and matrix metalloproteinases (MMPs). Secondary outcomes were changes in weight, BMI, 25(OH)D, calcium, phosphorous and parathyroid hormone (PTH). Sun exposure and dietary intakes were also assessed. Serum levels of 25(OH)D3 increased significantly with a simultaneous decrease in serum concentration of PTH in the vitamin D group. Weight, BMI, FSG, and MMP-9 decreased significantly in both groups, and there were significant differences in changes in weight, serum 25(OH)D3, PTH, and MMP-9 levels between the groups. Within- and between-groups analysis revealed no significant differences in serum calcium, phosphorous, serum insulin, HOMA-IR, QUICKI, and MMP-2 after intervention. Our results indicated that improvement in vitamin D status resulted in greater reductions in weight and MMP-9 during weight loss. These preliminary results are sufficient to warrant a bigger study group.


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