Glucose is a primary energy source for most cells and an important substrate for many biochemical reactions. As glucose is a need of each and every cell of the body, so are the glucose transporters. Consequently, all cells express these important proteins on their surface. In recent years developments in genetics have shed new light on the types and physiology of various glucose transporters, of which there are two main types-sodium-glucose linked transporters (SGLTs) and facilitated diffusion glucose transporters (GLUT)-which can be divided into many more subclasses. Transporters differ in terms of their substrate specificity, distribution and regulatory mechanisms. Glucose transporters have also received much attention as therapeutic targets for various diseases. In this review, we attempt to present a simplified view of this complex topic which may be of interest to researchers involved in biochemical and pharmacological research.

AbstractThe ketogenic diet (KD) has been successfully used for a century for treating refractory epilepsy and is currently seen as one of the few viable approaches to the treatment of a plethora of metabolic and neurodegenerative diseases. Empirical evidence notwithstanding, there is still no universal understanding of KD mechanism(s). An important fact is that the brain is capable of using ketone bodies for fuel. Another critical point is that glucose’s functions span beyond its role as an energy substrate, and in most of these functions, glucose is irreplaceable. By acting as a supplementary fuel, ketone bodies may free up glucose for its other crucial and exclusive function. We propose that this glucose-sparing effect of ketone bodies may underlie the effectiveness of KD in epilepsy and major neurodegenerative diseases, which are all characterized by brain glucose hypometabolism.

Proper brain function relies on an adequate supply of energy - mainly glucose - to power neuronal activity. Delivery of this nutrient to the neuropil is mediated by the Glucose Transporter1 (GLUT1) protein. Perturbing glucose supply to the brain is profoundly damaging and exemplified by the neurodevelopmental disorder, GLUT1 deficiency syndrome (GLUT1DS). Resulting from haploinsufficiency of the SLC2A1 (GLUT1) gene, GLUT1DS is characterized by intractable infantile-onset seizures and a disabling movement disorder. Ketogenic diets, which supply the brain with an alternate energy source, ketone bodies, are currently the preferred therapeutic option for Glut1DS patients but do not address the underlying cause - low brain glucose - of the disease. One intuitively appealing therapeutic strategy that does, involves restoring GLUT1 levels to the patient brain. Here, we demonstrate that transgenic expression of the human GLUT1 genomic locus in a mouse model of GLUT1DS raises brain GLUT1 levels and reduces disease burden. Augmenting GLUT1 levels in mutants correspondingly raised cerebrospinal fluid (CSF) glucose levels, improved motor performance and reduced the frequency of seizures characteristically observed in GLUT1DS. Interestingly, the increased GLUT1 in mutants harboring the human GLUT1 locus was at least partly the result of an increase in murine Slc2a1 (Glut1) activity, most likely the effect of a long non-coding RNA (lncRNA) embedded in the human transgene. Collectively, our work has not only shown that repleting human GLUT1 mitigates GLUT1DS but also has yielded transgenic mice that constitute a useful tool to test and optimize clinically promising agents designed to stimulate this gene for therapeutic purposes.

the risk of malnutrition. During prolonged fasting or very low calorie diets the reduction of blood glucose, the preferred energy source of the brain Dieting is the practice of eating food in a regulated way to decrease, maintain, or increase body weight, or to prevent and treat diseases such as diabetes and obesity. As weight loss depends on calorie intake, different kinds of calorie-reduced diets, such as those emphasising particular macronutrients (low-fat, low-carbohydrate, etc.), have been shown to be no more effective than one another. As Fasting is the act of intentional taking a long time interval between meals. Lengthy fasting (multiple days in a week) might be dangerous due to the risk of malnutrition. During prolonged fasting or very low calorie diets the reduction of blood glucose, the preferred energy source of the brain, causes the body to deplete its glycogen stores. Once glycogen is depleted the body begins to fuel the brain using ketones, while also metabolizing body protein (including but not limited to skeletal muscle) to be used to synthesize sugars for use as energy by the rest of the body. Most experts believe that a prolonged fast can lead to muscle wasting. The use of short-term fasting, or various forms of intermittent fasting, have been used as a form of dieting to circumvent the issues of long fasting. Intermittent fasting commonly takes the form of periodic fasting, alternate-day fasting, time-restricted feeding, and/or religious fasting. It can be a form of reduced-calorie dieting but pertains entirely to when the metabolism is activated during the day for digestion. The changes to eating habits on a regular basis do not have to be severe or absolutely restrictive to see benefits to cardiovascular health, such as improved glucose metabolism, reduced inflammation, and reduced blood pressure. Studies have suggested that for people in intensive care, an intermittent fasting regimen might "[preserve] energy supply to vital organs and tissues... [and] powerfully activates cell-protective and cellular repair pathways, including autophagy, mitochondrial biogenesis and antioxidant defenses, which may promote resilience to cellular stress." There is evidence demonstrating profound metabolic benefits of intermittent fasting in rodents. However, evidence is lacking or contradictory in humans and requires further investigation, especially over the long-term. Some evidence suggests that intermittent restriction of caloric intake has no weight-loss advantages over continuous calorie restriction plans. For adults, fasting diets appear to be safe and tolerable, however there is a possibility that periods of fasting and hunger could lead to overeating and to weight regain after the fasting…