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Vitamin D Receptor Polymorphisms and Diabetes Risk
Among adults with Prediabetes, vitamin D3 supplementation was associated with lower diabetes risk only in those with specific ApaI vitamin D receptor genotypes.
This genetic association analysis of the D2d study suggests that genetic variation in the VDR, specifically the ApaI polymorphism, is associated with diabetes risk at higher intratrial 25(OH)D levels and is associated with response to 4,000 IU/d of vitamin D3 supplementation among adults with prediabetes. Participants carrying the ApaI AA genotype did not experience a reduction in diabetes risk, either when achieving higher intratrial 25(OH)D concentrations or while being treated with 4,000 IU/d of vitamin D3. In contrast, those carrying the ApaI CC and AC genotypes, representing 71% of the D2d study population, had progressively lower risk of type 2 diabetes at intratrial 25(OH)D levels of 40 ng/mL or higher. Participants with these genotypes randomized to vitamin D3 had a 19% reduction in the risk of progression to diabetes compared with placebo, whereas those with ApaI AA alleles did not respond to treatment with vitamin D3. The BsmI polymorphism also appeared to play a role in the association between the achieved intratrial 25(OH)D level and diabetes risk, as expected given the high linkage disequilibrium of ApaI and BsmI (D’ = 1.0 and r2 = 1.0) among people of European ancestry.15 Because there was a near complete overlap between participants carrying the nonresponsive Bsml TT genotype and those carrying the nonresponsive ApaI AA genotype, knowing the ApaI genotype alone was sufficient to identify individuals who were likely—or unlikely—to respond to supplementation with 4,000 IU/d of vitamin D3. These exploratory genetic association findings support our hypothesis that a common VDR variant modulates the link between high intratrial 25(OH)D levels and diabetes risk, and the association between relatively high-dose vitamin D3 supplementation and diabetes risk among adults with prediabetes. The distributions of alleles of the 3 polymorphisms in the D2d study were similar to those reported in the UK Biobank of participants with prediabetes.5 Consistent with the UK Biobank study and other studies,5,16,17 the 25(OH)D levels achieved during the D2d trial did not differ significantly among participants with different VDR polymorphisms.
In the UK Biobank study, among adults with prediabetes and a median 25(OH)D level of 19.2 ng/mL (a value below our referent range of 20–29.9 ng/mL), there was a stepwise decrease in the risk of diabetes at 25(OH)D levels of lower than 10 (the study’s referent), 10 to 20, 20 to 30, and 30 ng/mL or higher.5 Risk reduction was present in all VDR genotypes of the 4 examined polymorphisms (ApaI, BsmI, TaqI, and FokI), but it was more prominent among those carrying the T allele of BsmI. There were too few participants in the D2d study with sufficiently low 25(OH)D levels to address this range of the 25(OH)D spectrum. Conversely, there were too few participants with sufficiently high 25(OH)D levels in the UK Biobank study to address the question posed in our study. To our knowledge, no other high-dose vitamin D trials among adults with prediabetes have examined how VDR polymorphisms may modify the effect of vitamin D supplementation on diabetes risk.
Our exploratory findings, if confirmed, hold promise for high-dose vitamin D3 as a targeted, personalized approach to reducing the risk of type 2 diabetes among selected adults with prediabetes. The magnitude of the observed risk reduction among participants with AC and CC alleles of the ApaI polymorphism, if confirmed in an independent clinical trial, would have clinical implications for the management of prediabetes. In the original report of the D2d trial,2 the HR for conversion to type 2 diabetes with vitamin D supplementation was 0.88 (95% CI, 0.72−1.04). The HR decreased to 0.81 (95% CI, 0.66−0.99) in our exploratory analysis when genetically nonresponsive participants (those with AA alleles of the ApaI polymorphism, comprising 29.5% of all participants) were excluded. If confirmed, a 19% risk reduction in conversion to type 2 diabetes with vitamin D3 supplementation would not be trivial. First, assessment of a single VDR polymorphism is inexpensive and now widely available.
Cav3.1 is a neuronal leucine sensor that mediates satiety and weight loss in response to dietary protein
Online now: Tsang et al. identify the T-type calcium channel Cav3.1 as a neuronal leucine sensor in hypothalamic POMC neurons. Leucine directly binds Cav3.1, lowering its activation threshold. Loss of Cav3.1 in POMC neurons abolishes high-protein diet-induced appetite suppression, while pharmacological activation promotes weight loss and potentiates the effects of anorectic agents.
What if humans could regrow tissue? New study moves science closer
For centuries, the inability to regrow lost body parts has been considered a defining limitation of humans and other mammals. While animals like salamanders can regenerate entire limbs, humans are left with scar tissue. But new research from the Texas A&M College of Veterinary Medicine and Biomedical Sciences (VMBS) suggests that this limitation may not be permanent. Instead, the capacity for regeneration may still exist—hidden within the body’s normal healing process.
“Why some animals can regenerate and others, particularly humans, can’t is a big question that has been asked since Aristotle,” said Dr. Ken Muneoka, a professor in the VMBS’ Department of Veterinary Physiology & Pharmacology (VTPP). “I’ve spent my career trying to understand that.”
In their study, published in Nature Communications, Muneoka and his colleagues detail a newly developed two-step treatment that led to the regeneration of bone, joint structures and ligaments. While the results were imperfect, the team believes this approach could be used more immediately to reduce scarring and improve tissue repair after amputations.
NASA Rover Uncovers Rare Organic Molecules on Mars
“We think we’re looking at organic matter that’s been preserved on Mars for 3.5 billion years,” said Dr. Amy Williams. [ https://www.labroots.com/trending/space/30462/nasa-rover-unc…les-mars-2](https://www.labroots.com/trending/space/30462/nasa-rover-unc…les-mars-2)
Does Mars contain the building blocks for life as we know it? This is what a recent study published in Nature Communications hopes to address as a team of researchers investigated whether the surface of Mars could preserve evidence for life as we know it using experiments from one of its rovers. This study has the potential to help scientists better understand how and where to search for past evidence of life as we know it and comes as NASA is working to return samples from the surface of Mars.
For the study, the researchers examined data obtained from NASA’s Curiosity rover, which has been exploring Gale Crater on Mars since 2012. Recently, it used its cache of scientific instruments to identify more than 20 organic molecules from 3.5-billion-year-old Martian clays. These included a first-time identification of DNA precursors and specific chemicals that are delivered to planets via meteorites.
UV Camera Captures Glowing Coronae on Leaves During Storms
“It’s nearly invisible to the naked eye but our instruments give rise to a vision of swaths of scintillating corona glowing as thunderstorms pass overhead,” said Patrick McFarland. [ https://www.labroots.com/trending/earth-and-the-environment/…s-storms-2](https://www.labroots.com/trending/earth-and-the-environment/…s-storms-2)
Can storms cause electrical discharges on trees? This is something that has eluded scientists for decades, but a recent study published in Geophysical Research Letters might finally have an answer as a team of researchers collected first-time images of trees emanating ultraviolet (UV) light during a thunderstorm. This study has the potential to help scientists better understand how weather could affect plants worldwide.
For the study, the researchers traveled to Florida, which is known for its frequent and powerful thunderstorms, with the goal of imaging electric pulses that appear at the tips of trees during such storms. The primary motivation behind the study was to provide direct evidence of an atmospheric phenomenon that had been hypothesized since the 1930s but never captured in nature. During this time, scientists suspected that trees emit light during thunderstorms due to the electrical discharges but never had direct evidence.
Using a customized camera capable of capturing only corona light, lightning, and fire, this team of researchers successfully captured first-time evidence of trees emitting UV light during a Florida thunderstorm. These findings are crucial in helping researchers better understand the link between atmospheric electricity and forest ecology.
Western U.S. water supply at risk as snow turns to rain
“This study provides a crucial step in improving projections of water resource responses to climate change and underscores the value of integrating water transit time dynamics into future hydrologic assessments,” said Zachariah Butler. [ https://www.labroots.com/trending/earth-and-the-environment/…now-rain-2](https://www.labroots.com/trending/earth-and-the-environment/…now-rain-2)
How can climate change impact how fast snow turns into water? This is what a recent study published in Scientific Reports hopes to address as a team of scientists investigated snow drought conditions and how this could lead to poor water quality. This study has the potential to help scientists, legislators, and the public better understand the negative impacts of climate change on water management systems and how to mitigate them.
For the study, the researchers analyzed a combination of data from historical (2006−2013) and future (2086−2093) estimates from five regions in the U.S. Pacific Northwest for rain-snow transition times. The motivation behind the study comes from a knowledge gap regarding how climate change impacts the speed of water as it transitions from snow to rain, as opposed to simply the amount of water.
In the end, the researchers found that water transit times were estimated to be an average of 18 percent higher in the late 21st century if present climate change continues. These findings indicate that higher water transit times when snow becomes rainwater could result in greater levels of water contaminants due to shallower water getting into local water supplies.
Autoinhibitory control of MLKL governs pseudokinase domain phosphorylation and oligomerization during necroptosis
The current model of necroptosis assumes that MLKL’s N-terminal cytotoxic domain is unleashed from autoinhibition concurrent with phosphorylation by RIPK3. Here, Pan and Abbott show that inhibition of MLKL’s N terminus abolishes phosphorylation by RIPK3 whereas removal or relieving autoinhibition between the N-terminal and intermediate domains promotes its phosphorylation.
Supporting the concept that GLP1 agonist drugs lower BloodPressure independent from their weight loss effects
Daniel J. Drucker & team identify the vascular smooth muscle GLP-1 receptor as a key cellular target for the actions of GLP-1 medicines to lower blood pressure.
The figure: Renal GLP1R/Glp1r is expressed in human and murine vascular smooth muscle cells (VSMCs) and Glp1rVSM-/- mice have reduced Glp1r transcripts in renal tissues.
1Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
2Section of Nephrology, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.
Address correspondence to: Daniel J. Drucker, Mt. Sinai Hospital, 600 University Ave. Mailbox 39, Toronto, Ontario, Canada, M5G1X5. Phone: 416.361.2661; Email: [email protected].