scholarly journals A study of the effects of large dose of parenteral vitamin D (D3) on insulin resistance in type 2 DM patients

2017 ◽  
Vol 5 (6) ◽  
pp. 2338
Author(s):  
Vinu Jamwal ◽  
Wani Zahid Hussain ◽  
Abhinav Gupta ◽  
Anil K. Gupta
Keyword(s):  
Insulin Resistance ◽  
Vitamin D ◽  
Insulin Sensitivity ◽  
Vitamin D3 ◽  
Favourable Effect ◽  
P Value ◽  
Low Grade ◽  
Β Cells ◽  
Pancreatic Β Cells

Background: Over the past decade, vitamin D is more known as a hormone because of its extra - skeletal outcomes in various disease conditions, including diabetes. Most cells, including the pancreatic β-cells, contain the vitamin D receptor and they also have the capability to produce the biologically active 1,25-dihydroxyvitamin D [1,25(OH)2D3] which allows intracrine and paracrine functions. In vitro studies have shown that the active vitamin D metabolite 1,25(OH)2D stimulated insulin release by the pancreatic β-cells. Vitamin D is known to have immune modulatory and anti-inflammatory effects and reduces peripheral insulin resistance by altering low-grade chronic inflammation. This study was done to assess whether supplementation of vitamin D in type 2 diabetes mellitus (T2DM) patients with Vitamin D deficiency has any favourable effect on insulin resistance.Methods: It was a short term interventional study conducted at ASCOMS hospital Jammu including a total of 50 vitamin D deficient [25(OH) D <50 nmol/l] T2DM patients with an in-adequate glycemic control (HbA1c > 7.0%). All the 50 study participants completed the study and there were no changes either in anti-hyperglycemic drugs (including insulin) or antihypertensive drugs being used. After supplementation with a single high dose (600000 IU) of parenteral vitamin D3 changes in HOMA-IR (Homeostasis model assessment insulin resistance) were seen on follow up at 3 months.Results: Vitamin D3 supplementation improved insulin sensitivity, HOMA-IR decreased from 4.05±1.42 to 3.93±1.28 (p =0.011). It decreased equally in males (3.85±1.43 to 3.76±1.30) (p value=0.023) and females (4.24±1.42 to 4.10±1.27) (p value=0.021). HOMA-IR showed negative association with Vitamin D levels both at baseline and after 3 months of follow up.Conclusions: This improvement in insulin sensitivity is evidenced in our study by decrease in fasting insulin levels (FIL) and improvement in fasting blood sugars (FBS). It is due to both direct and indirect effects of Vitamin D3 on both insulin sensitivity and secretion.

Specific Deletion of CASK in Pancreatic β Cells Affects Glucose Homeostasis and Improves Insulin Sensitivity in Obese Mice by Reducing Hyperinsulinemia Running Title: β Cell CASK Deletion Reduces Hyperinsulinemia

2021 ◽  
Author(s):  
Xingjing Liu ◽  
Peng Sun ◽  
Qingzhao Yuan ◽  
Jinyang Xie ◽  
Ting Xiao ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Homeostasis ◽  
Chow Diet ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Calcium Calmodulin Dependent ◽  
Normal Chow

Calcium/calmodulin-dependent serine protein kinase (CASK) is involved in the secretion of insulin vesicles in pancreatic β-cells. The present study revealed a new <i>in vivo </i>role of CASK in glucose homeostasis during the progression of type 2 diabetes mellitus (T2DM). A Cre-loxP system was used to specifically delete the <i>Cask </i>gene in mouse β-cells (βCASKKO), and the glucose metabolism was evaluated in <a>βCASKKO</a> mice fed a normal chow diet (ND) or a high-fat diet (HFD). ND-fed mice exhibited impaired insulin secretion in response to glucose stimulation. Transmission electron microscopy showed significantly reduced numbers of insulin granules at or near the cell membrane in the islets of βCASKKO mice. By contrast, HFD-fed βCASKKO mice showed reduced blood glucose and a partial relief of hyperinsulinemia and insulin resistance when compared to HFD-fed wildtype mice. The IRS1/PI3K/AKT signaling pathway was upregulated in the adipose tissue of HFD-βCASKKO mice. These results indicated that knockout of the <i>Cask</i> gene in β cells had a diverse effect on glucose homeostasis: reduced insulin secretion in ND-fed mice, but improves insulin sensitivity in HFD-fed mice. Therefore, CASK appears to function in the insulin secretion and contributes to hyperinsulinemia and insulin resistance during the development of obesity-related T2DM.

scholarly journals Selenoprotein P as a significant regulator of pancreatic β cell function

2019 ◽  
Author(s):  
Yoshiro Saito
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Insulin Signalling ◽  
Selenoprotein P ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Β Cell Function

Abstract Selenoprotein P (SeP; encoded by SELENOP) is selenium (Se)-rich plasma protein that is mainly produced in the liver. SeP functions as a Se-transport protein to deliver Se from the liver to other tissues, such as the brain and testis. The protein plays a pivotal role in Se metabolism and antioxidative defense, and it has been identified as a ‘hepatokine’ that causes insulin resistance in type 2 diabetes. SeP levels are increased in type 2 diabetes patients, and excess SeP impairs insulin signalling, promoting insulin resistance. Furthermore, increased levels of SeP disturb the functioning of pancreatic β cells and inhibit insulin secretion. This review focuses on the biological function of SeP and the molecular mechanisms associated with the adverse effects of excess SeP on pancreatic β cells’ function, particularly with respect to redox reactions. Interactions between the liver and pancreas are also discussed.

scholarly journals Association of Vitamin D with Type 2 Diabetes in Postmenopausal Females in Saudi Arabia

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Shatha Alharazy ◽  
Eman Alissa ◽  
Mohammed Ardawi ◽  
Susan Lanham-New ◽  
M. Denise Robertson
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Vitamin D ◽  
Saudi Arabia ◽  
Insulin Sensitivity ◽  
Postmenopausal Women ◽  
Cell Activity ◽  
Study Cohort ◽  
Model Assessment

AbstractVitamin D (vitD) deficiency has been suspected as a risk factor for type 2 diabetes mellitus (T2DM). It has been reported that an inverse relationship exists between vitD status and risk of T2DM. The aim of this study was to investigate whether there is an association between vitD status and glycemic profile and other metabolic parameters among postmenopausal women with T2DM (living in Saudi Arabia). A cross-sectional study was conducted at King Fahad Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia. One thirty six (n = 136) postmenopausal females (age ≥ 50 years) living in Jeddah city, Saudi Arabia, with T2DM were randomly recruited in this study. Anthropometric measures, blood pressure readings and fasting blood samples were obtained fro all study participants. Several biochemical parameters were estimated in fasting serum samples including total 25(OH)D, HbA1c, insulin, glucose, c-peptide and lipid profile. Surrogate markers for insulin resistance were calculated using Homeostasis Model Assessment for insulin resistance and beta cell activity (HOMA-IR, HOMA-β), Quantitative insulin sensitivity check index (QUICK-I) and McAuley's index. VitD deficiency was defined as serum total 25(OH)D level below 20 ng/ml.The Mean (± SD) serum levels of total 25(OH)D were 13.8 ± 8.6 ng/ml with 79% of the study cohort being vitD deficient. Furthermore, serum total 25(OH)D levels were found to be inversely correlated with fasting insulin (r = -0.24, p = 0.029), HOMA-IR (r = -0.24, p = 0.03), and positively correlated with McAuley's index (r = 0.22, p = 0.048) and QUICK-I (r = 0.25, p = 0.024). In conclusion, vitD deficiency is highly prevalent among postmenopausal women with T2DM living in Jeddah, Saudi Arabia. VitD was found to be associated with insulin resistance. Whether vitD supplements are able to improve insulin sensitivity and other parameters in T2DM postmenopausal women should be further investigated.

scholarly journals A Review of the Effect of Vitamin D3 Supplementation on Insulin Response in Adults With Overweight or Obesity

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1312-1312
Author(s):  
Kimberly Gaskill ◽  
Madeline Bartzis ◽  
Annalyse Boucher ◽  
Kristin Lawton ◽  
Rex Liang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Vitamin D ◽  
Insulin Sensitivity ◽  
Lifestyle Intervention ◽  
Vitamin D3 ◽  
Insulin Response ◽  
Inverse Association ◽  
Vitamin D Status ◽  
Vitamin D3 Supplementation ◽  
Overweight Or Obesity

Abstract Objectives There is an inverse association between serum vitamin D and excess body weight, insulin resistance, β-cell dysfunction, and the risk of developing type 2 diabetes (T2DM). Given that inadequate vitamin D is common in adults with overweight or obesity, vitamin D supplementation may improve insulin response. The aim of this review was to investigate whether vitamin D3 supplementation in excess of the Recommended Daily Allowance (RDA: 600 IU/day) improves insulin sensitivity or reduces insulin resistance in adults with overweight or obesity and no prior diagnosis of T2DM. Methods A literature search was conducted using PubMed and CINAHL with the following search terms: ((vitamin D OR cholecalciferol supplement*) AND (overweight OR obes*) AND (insulin resistance OR insulin sensitivity)). The initial search generated 806 unduplicated articles. Filters and exclusions were applied; 171 articles were screened, 40 were reviewed in full-text and 5 randomized control trials published between 2015–2020 met inclusion criteria for the review. Results In all five studies, vitamin D3 supplementation in excess of the RDA for ≥3 months corrected vitamin D status, with no adverse effects, among the majority of subjects. Two studies provided a lifestyle intervention in addition to vitamin D3 at 25,000 and 50,000 IU/week for ≥3 months and significantly (p &lt; 0.001 and p = 0.04 respectively) improved insulin sensitivity in adults with overweight or obesity and vitamin D deficiency. However, no significant effects on insulin response were observed in the other three studies. Conclusions High-dose vitamin D3 was effective in repleting vitamin D status in adults with overweight or obesity and inadequate vitamin D levels, and should be recommended per Endocrine Society clinical practice guidelines. Furthermore, vitamin D3 supplementation in excess of the RDA for ≥3 months combined with a lifestyle intervention may have a beneficial effect on insulin response in adults who are at risk for T2DM. Funding Sources None.

scholarly journals A Novel Resolution of Diabetes: C-C Chemokine Motif Ligand 4 Is a Common Target in Different Types of Diabetes by Protecting Pancreatic Islet Cell and Modulating Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Ting-Ting Chang ◽  
Liang-Yu Lin ◽  
Jaw-Wen Chen
Keyword(s):  
Insulin Resistance ◽  
Blood Sugar ◽  
Islet Cell ◽  
Diabetic Mice ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Type 2 Dm ◽  
Tnf Α

Systemic inflammation is related to hyperglycemia in diabetes mellitus (DM). C-C chemokine motif ligand (CCL) 4 is upregulated in type 1 &amp; type 2 DM patients. This study aimed to investigate if CCL4 could be a potential target to improve blood sugar control in different experimental DM models. Streptozotocin-induced diabetic mice, Leprdb/JNarl diabetic mice, and C57BL/6 mice fed a high fat diet were used as the type 1 DM, type 2 DM, and metabolic syndrome model individually. Mice were randomly assigned to receive an anti-CCL4 neutralizing monoclonal antibody. The pancreatic β-cells were treated with streptozotocin for in vitro experiments. In streptozotocin-induced diabetic mice, inhibition of CCL4 controlled blood sugar, increased serum insulin levels, increased islet cell proliferation and decreased pancreatic interleukin (IL)-6 expression. In the type 2 diabetes and metabolic syndrome models, CCL4 inhibition retarded the progression of hyperglycemia, reduced serum tumor necrosis factor (TNF)-α and IL-6 levels, and improved insulin resistance via reducing the phosphorylation of insulin receptor substrate-1 in skeletal muscle and liver tissues. CCL4 inhibition directly protected pancreatic β-cells from streptozotocin stimulation. Furthermore, CCL4-induced IL-6 and TNF-α expressions could be abolished by siRNA of CCR2/CCR5. In summary, direct inhibition of CCL4 protected pancreatic islet cells, improved insulin resistance and retarded the progression of hyperglycemia in different experimental models, suggesting the critical role of CCL4-related inflammation in the progression of DM. Future experiments may investigate if CCL4 could be a potential target for blood sugar control in clinical DM.

scholarly journals Vitamin D 3, osteoprotegerin and other hormonal and metabolic parameters in female patients with type 2 diabetes

2012 ◽  
Vol 9 (4) ◽  
pp. 23-27 ◽  
Author(s):  
A F Verbovoi ◽  
L A Sharonova ◽  
A V Kapishnikov ◽  
D V Demidova
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Vitamin D ◽  
Vitamin D3 ◽  
Metabolic Parameters ◽  
Female Patients ◽  
Vitamin D 3 ◽  
Diabetes And Obesity

The article presents the results of evaluation of vitamin D3, osteoprotegerin, carbohydrate and fat metabolic parameters in women with type 2 diabetes and obesity. The study subjects showed an increase of osteoprotegerin, decrease of vitamin D3, insulin resistance and compensatory hyperinsulinemia.

scholarly journals Association Between Vitamin D and Glycaemic Parameters in a Multi-Ethnic Cohort of Postmenopausal Women with Type-2 Diabetes in Saudi Arabia

2021 ◽  
Author(s):  
Shatha Alharazy ◽  
Eman Alissa ◽  
Susan Lanham-New ◽  
Muhammad Imran Naseer ◽  
Adeel G. Chaudhary ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Vitamin D ◽  
Saudi Arabia ◽  
Insulin Sensitivity ◽  
Postmenopausal Women ◽  
C Peptide ◽  
Population Groups ◽  
The Relationship

Abstract Background: The relationship between Vitamin D (VitD) with insulin sensitivity and secretion in Type-2 diabetes (T2D) has shown to be different amongst different ethnic populations. In Saudi Arabia, where both T2D and VitD deficiency are highly prevalent health concerns, little is known about the relationship between VitD, insulin sensitivity, resistance and the relative importance of ethnicity. Our aim in this study is to investigate influence of ethnicity on VitD association with glycaemic profile primarily and to measures of obesity secondarily, among multiethnic postmenopausal women with T2DM in Saudi Arabia.Methods: A cross-sectional study was conducted at King Fahad Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia. Postmenopausal females (n = 173, age ≥ 50 years) with T2D were randomly selected in this study. Anthropometric measures and fasting blood samples were obtained for all study participants. Several biochemical parameters were measured including 25-hydroxyvitamin D (25(OH)D), glycosylated hemoglobin (HbA1c), insulin, glucose and c-peptide. Surrogate markers for insulin resistance were calculated using Homeostasis Model Assessment 2 for insulin resistance and beta cell activity (HOMA2-IR, HOMA2-β).Results: Overall, 25(OH)D was inversely associated with fasting glucose (r=-0.165, P=0.037), insulin (r=-0.184, P=0.02), C-peptide (r=-0.19, P=0.015) and HOMA2- IR C-peptide (r=-0.23,P=0.004). Additionally, serum 25 (OH)D showed an overall a negative correlation with body weight (r=-0.173 P=0.028), waist and hip circumferences (r=-0.167, P=0.033; r=-0.22, P=0.004 respectively) but not with body mass index (BMI) or waist hip ration (WHR). In the white ethnic group but not in black or Asian population groups, 25(OH)D level was associated with only serum fasting C-peptide and HOMA2-IR C-peptide and BMI (P<0.05). Conclusions: Insulin resistance and obesity are associated with VitD status in T2D in this cohort. Our findings also suggest that these VitD associations in women from white ethnic background are different than in those from black/Asian ethnic backgrounds. Whether VitD supplements are able to improve degree of obesity and insulin sensitivity should be further investigated in different ethnic population groups.

scholarly journals THE ROLE OF VITAMIN D IN THE PATHOGENESIS OF CHRONIC NON-COMMUNICABLE DISEASES

2014 ◽  
Vol 17 (3) ◽  
pp. 27-30 ◽  
Author(s):  
L V Egshatyan ◽  
E N Dudinskaya ◽  
O N Tkacheva ◽  
D A Kashtanova
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Vitamin D ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Autoimmune Destruction ◽  
Near Future ◽  
Reduced Risk

This review shows the role of vitamin D in the regulation of not only the level of calcium, but also in the pathogenesis of chronic systemic inflammation, disruption of insulin sensitivity of tissues. The sufficient levels of vitamin D in the blood can lead to reduced risk of developing type 2 diabetes, obesity, autoimmune destruction of pancreatic β-cells, certain cardiometa-bolic risk factors, and therefore cardiovascular disease. Perhaps preparations of vitamin D in the near future may become additional and necessary nutritional substances for correction of insulin resistance, cardiovascular disease, chronic inflammation and prevention of disorders of glucose metabolism.

Vitamin D and new insights into pathophysiology of type 2 diabetes

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Karel Vondra ◽  
Richard Hampl
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Inflammatory Cytokines ◽  
Vitamin D Supplementation ◽  
Low Grade ◽  
Peripheral Tissues ◽  
Functional Inactivation

Abstract Deficiency in vitamin D plays a role in the onset and development of insulin resistance (IR) and type 2 diabetes (T2DM). A normal level of vitamin D is able to reduce low grade inflammation, which is a major process in inducing insulin resistance. It is also engaged in maintaining low resting levels of reactive species and radicals, normal Ca2+ signaling, a low expression of pro-inflammatory cytokines but increased formation of anti-inflammatory cytokines. Vitamin D is also able to prevent hypermethylation (of DNA) and consequent functional inactivation of many genes, as well as other epigenetic alterations in β cells and in other insulin-sensitive peripheral tissues, mainly liver, adipose tissue and muscle. Vitamin D deficiency thus belongs to key factors accelerating the development of IR and consequently T2DM as well. However, vitamin D supplementation aimed at the control of glucose homeostasis in humans showed controversial effects. As a result, further studies are running to gain more detailed data needed for the full clinical utilization of vitamin D supplementation in the prevention and treatment of T2DM. Until new results are published, supplementation with high doses of vitamin D deficiency is not recommended. However, prevention of vitamin D deficiency and its correction are highly desired.

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