An overview of type 2 diabetes and importance of vitamin D3-vitamin D receptor interaction in pancreatic β-cells

2018 ◽  
Vol 32 (4) ◽  
pp. 429-443 ◽  
Author(s):  
Abraham Neelankal John ◽  
Fang-Xu Jiang
Author(s):  
Vinu Jamwal ◽  
Wani Zahid Hussain ◽  
Abhinav Gupta ◽  
Anil K. Gupta

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.


2021 ◽  
Vol 22 (3) ◽  
pp. 1059
Author(s):  
Bodo C. Melnik

Epidemiological studies associate milk consumption with an increased risk of Parkinson’s disease (PD) and type 2 diabetes mellitus (T2D). PD is an α-synucleinopathy associated with mitochondrial dysfunction, oxidative stress, deficient lysosomal clearance of α-synuclein (α-syn) and aggregation of misfolded α-syn. In T2D, α-syn promotes co-aggregation with islet amyloid polypeptide in pancreatic β-cells. Prion-like vagal nerve-mediated propagation of exosomal α-syn from the gut to the brain and pancreatic islets apparently link both pathologies. Exosomes are critical transmitters of α-syn from cell to cell especially under conditions of compromised autophagy. This review provides translational evidence that milk exosomes (MEX) disturb α-syn homeostasis. MEX are taken up by intestinal epithelial cells and accumulate in the brain after oral administration to mice. The potential uptake of MEX miRNA-148a and miRNA-21 by enteroendocrine cells in the gut, dopaminergic neurons in substantia nigra and pancreatic β-cells may enhance miRNA-148a/DNMT1-dependent overexpression of α-syn and impair miRNA-148a/PPARGC1A- and miRNA-21/LAMP2A-dependent autophagy driving both diseases. MiRNA-148a- and galactose-induced mitochondrial oxidative stress activate c-Abl-mediated aggregation of α-syn which is exported by exosome release. Via the vagal nerve and/or systemic exosomes, toxic α-syn may spread to dopaminergic neurons and pancreatic β-cells linking the pathogenesis of PD and T2D.


Author(s):  
Nancy Taneja ◽  
Rajesh Khadgawat ◽  
Shalini Mani

  Objective: Vitamin D receptor (VDR) mediated Vitamin D signaling is important for expression of insulin gene and glucose transporters, which help in glucose uptake by cells. Current evidence suggests that four common polymorphisms (FokI, BsmI, ApaI, TaqI) of VDR gene are associated with Type 2 diabetes mellitus (T2DM) in different populations. However, there is a scarcity of data on VDR polymorphisms from Indian population.Methods: In the current study, total genomic DNA was isolated from 100 well-characterized T2DM patients and 100 healthy controls. We investigated the prevalence of FokI and ApaI polymorphisms in VDR gene of these patients by polymerase chain reaction-restriction fragment length polymorphism-based method. Taking help of our previous published data on TaqI and BsmI polymorphisms in same patients, the haplotype study was also conducted. Statistical analysis of data was performed using SPSS 21.0 software. Haplotype and linkage disequilibrium analysis was performed by Haploview software.Results: Both the wild (TT) and mutant (CC) genotype of FokI polymorphism showed a significant difference between patients and controls (p<0.001 and p<0.001, respectively). The frequency of mutant allele (C) was also significantly higher in T2DM patients than the controls (p<0.001). In case of ApaI, frequency of wild (GG) and mutant (CC) genotype was significantly different in patients and controls (p=0.017 and p=0.034). As per haplotype analysis, the CACT haplotype was predicted to be of significance in patients and consists of mutant alleles of three polymorphisms (FokI, BsmI, ApaI). Conclusion: Our study supports the association of FokI and ApaI polymorphism in T2DM. The haplotype analysis also indicates that the combinations of mutant allele of different VDR polymorphisms are probably responsible for increased susceptibility of these individuals toward T2DM.


Biology ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 128
Author(s):  
Yaser Albadr ◽  
Andrew Crowe ◽  
Rima Caccetta

The prevalence of type 2 diabetes mellitus is rising globally and this disease is proposed to be the next pandemic after COVID-19. Although the cause of type 2 diabetes mellitus is unknown, it is believed to involve a complex array of genetic defects that affect metabolic pathways which eventually lead to hyperglycaemia. This hyperglycaemia arises from an inability of the insulin-sensitive cells to sufficiently respond to the secreted insulin, which eventually results in the inadequate secretion of insulin from pancreatic β-cells. Several treatments, utilising a variety of mechanisms, are available for type 2 diabetes mellitus. However, more medications are needed to assist with the optimal management of the different stages of the disease in patients of varying ages with the diverse combinations of other medications co-administered. Throughout modern history, some lead constituents from ancient medicinal plants have been investigated extensively and helped in developing synthetic antidiabetic drugs, such as metformin. Teucrium polium L. (Tp) is a herb that has a folk reputation for its antidiabetic potential. Previous studies indicate that Tp extracts significantly decrease blood glucose levels r and induce insulin secretion from pancreatic β-cells in vitro. Nonetheless, the constituent/s responsible for this action have not yet been elucidated. The effects appear to be, at least in part, attributable to the presence of selected flavonoids (apigenin, quercetin, and rutin). This review aims to examine the reported glucose-lowering effect of the herb, with a keen focus on insulin secretion, specifically related to type 2 diabetes mellitus. An analysis of the contribution of the key constituent flavonoids of Tp extracts will also be discussed.


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