Showing papers by "Michael J. Berridge published in 2017"

Vitamin D deficiency and diabetes.

Abstract: Vitamin D deficiency has been linked to the onset of diabetes. This review summarizes the role of Vitamin D in maintaining the normal release of insulin by the pancreatic beta cells (β-cells). Diabetes is initiated by the onset of insulin resistance. The β-cells can overcome this resistance by releasing more insulin, thus preventing hyperglycaemia. However, as this hyperactivity increases, the β-cells experience excessive Ca2+ and reactive oxygen species (ROS) signalling that results in cell death and the onset of diabetes. Vitamin D deficiency contributes to both the initial insulin resistance and the subsequent onset of diabetes caused by β-cell death. Vitamin D acts to reduce inflammation, which is a major process in inducing insulin resistance. Vitamin D maintains the normal resting levels of both Ca2+ and ROS that are elevated in the β-cells during diabetes. Vitamin D also has a very significant role in maintaining the epigenome. Epigenetic alterations are a feature of diabetes by which many diabetes-related genes are inactivated by hypermethylation. Vitamin D acts to prevent such hypermethylation by increasing the expression of the DNA demethylases that prevent hypermethylation of multiple gene promoter regions of many diabetes-related genes. What is remarkable is just how many cellular processes are maintained by Vitamin D. When Vitamin D is deficient, many of these processes begin to decline and this sets the stage for the onset of diseases such as diabetes.

Vitamin D and Depression: Cellular and Regulatory Mechanisms

Abstract: Depression is caused by a change in neural activity resulting from an increase in glutamate that drives excitatory neurons and may be responsible for the decline in the activity and number of the GABAergic inhibitory neurons. This imbalance between the excitatory and inhibitory neurons may contribute to the onset of depression. At the cellular level there is an increase in the concentration of intracellular Ca2+ within the inhibitory neurons that is driven by an increase in entry through the NMDA receptors (NMDARs) and through activation of the phosphoinositide signaling pathway that generates inositol trisphosphate (InsP3) that releases Ca2+ from the internal stores. The importance of these two pathways in driving the elevation of Ca2+ is supported by the fact that depression can be alleviated by ketamine that inhibits the NMDARs and scopolamine that inhibits the M1 receptors that drive InsP3/Ca2+ pathway. This increase in Ca2+ not only contributes to depression but it may also explain why individuals with depression have a strong likelihood of developing Alzheimer's disease. The enhanced levels of Ca2+ may stimulate the formation of Aβ to initiate the onset and progression of Alzheimer's disease. Just how vitamin D acts to reduce depression is unclear. The phenotypic stability hypothesis argues that vitamin D acts by reducing the increased neuronal levels of Ca2+ that are driving depression. This action of vitamin D depends on its function to maintain the expression of the Ca2+ pumps and buffers that reduce Ca2+ levels, which may explain how it acts to reduce the onset of depression.

Vitamin D deficiency accelerates ageing and age-related diseases: a novel hypothesis

Abstract: Ageing can occur at different rates, but what controls this variable rate is unknown Here I have developed a hypothesis that vitamin D may act to control the rate of ageing The basis of this hypothesis emerged from studyng the various cellular processes that control ageing These processes such as autophagy, mitochondrial dysfunction, inflammation, oxidative stress, epigenetic changes, DNA disorders and alterations in Ca2+ and reactive oxygen species (ROS) signalling are all known to be regulated by vitamin D The activity of these processes will be enhanced in individuals that are deficient in vitamin D Not only will this increase the rate of ageing, but it will also increase the probability of developing age-related diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis and cardiovascular disease In individual with normal vitamin D levels, these ageing-related processes will occur at lower rates resulting in a reduced rate of ageing and enhanced protection against these age-related diseases