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Comprehensive Physiology

Kartik Mani, Ali Javaheri, Abhinav Diwan
Adaptive responses that counter starvation have evolved over millennia to permit organismal survival, including changes at the level of individual organelles, cells, tissues, and organ systems. In the past century, a shift has occurred away from disease caused by insufficient nutrient supply toward overnutrition, leading to obesity and diabetes, atherosclerosis, and cardiometabolic disease. The burden of these diseases has spurred interest in fasting strategies that harness physiological responses to starvation, thus limiting tissue injury during metabolic stress...
September 14, 2018: Comprehensive Physiology
Caglar Doguer, Jung-Heun Ha, James F Collins
Iron and copper have similar physiochemical properties; thus, physiologically relevant interactions seem likely. Indeed, points of intersection between these two essential trace minerals have been recognized for many decades, but mechanistic details have been lacking. Investigations in recent years have revealed that copper may positively influence iron homeostasis, and also that iron may antagonize copper metabolism. For example, when body iron stores are low, copper is apparently redistributed to tissues important for regulating iron balance, including enterocytes of upper small bowel, the liver, and blood...
September 14, 2018: Comprehensive Physiology
Hamid M Said, Ebba Nexo
Nine compounds are classified as water-soluble vitamins, eight B vitamins and one vitamin C. The vitamins are mandatory for the function of numerous enzymes and lack of one or more of the vitamins may lead to severe medical conditions. All the vitamins are supplied by food in microgram to milligram quantities and in addition some of the vitamins are synthesized by the intestinal microbiota. In the gastrointestinal tract, the vitamins are liberated from binding proteins and for some of the vitamins modified prior to absorption...
September 14, 2018: Comprehensive Physiology
Benoit P Delhaye, Katie H Long, Sliman J Bensmaia
The sense of proprioception allows us to keep track of our limb posture and movements and the sense of touch provides us with information about objects with which we come into contact. In both senses, mechanoreceptors convert the deformation of tissues-skin, muscles, tendons, ligaments, or joints-into neural signals. Tactile and proprioceptive signals are then relayed by the peripheral nerves to the central nervous system, where they are processed to give rise to percepts of objects and of the state of our body...
September 14, 2018: Comprehensive Physiology
Saverio Cinti
During the last decades, research on adipose tissues has spread in parallel with the extension of obesity. Several observations converged on the idea that adipose tissues are organized in a large organ with endocrine and plastic properties. Two parenchymal components: white (WATs) and brown adipose tissues (BATs) are contained in subcutaneous and visceral compartments. Although both have endocrine properties, their function differs: WAT store lipids to allow intervals between meals, BAT burns lipids for thermogenesis...
September 14, 2018: Comprehensive Physiology
Alice E Adriaenssens, Frank Reimann, Fiona M Gribble
The enteroendocrine system of the gut acts both locally and peripherally, regulating gastrointestinal function as well as metabolism, energy expenditure, and central appetite control through the release of a variety of hormones. The chemosensing ability of enteroendocrine cells is integral to their role in eliciting physiological changes in response to fluctuations in the composition of the intestinal lumen. Regulation of enteroendocrine cell activity is complex, and requires that these cells can integrate signals deriving from dietary sources as well as the nervous and endocrine systems...
September 14, 2018: Comprehensive Physiology
Norberto C Gonzalez, Ichiro Kuwahira
The objective of this article is to compare and contrast the known characteristics of the systemic O2 transport of humans, rats, and mice at rest and during exercise in normoxia and hypoxia. This analysis should help understand when rodent O2 transport findings can-and cannot-be applied to human responses to similar conditions. The O2 -transport system was analyzed as composed of four linked conductances: ventilation, alveolo-capillary diffusion, circulatory convection, and tissue capillary-cell diffusion. While the mechanisms of O2 transport are similar in the three species, the quantitative differences are naturally large...
September 14, 2018: Comprehensive Physiology
André Tchernof, Dannick Brochu, Ina Maltais-Payette, Mohamed Fouad Mansour, Geneviève B Marchand, Anne-Marie Carreau, Jordanna Kapeluto
The sexual dimorphism in human body fat distribution suggests a causal role for sex hormones. This is of particular importance when considering the role of excess visceral adipose tissue accumulation as a critical determinant of obesity-related cardiometabolic alterations. Scientific literature on the modulation of body fat distribution by androgens in humans is abundant, remarkably inconsistent and difficult to summarize. We reviewed relevant literature on this topic, with a particular emphasis on androgen replacement, androgen effects on selected parameters of adipose tissue function and adipose tissue steroid-converting enzymes...
September 14, 2018: Comprehensive Physiology
Vazhaikkurichi M Rajendran, Geoffrey I Sandle
The colon has large capacities for K+ absorption and K+ secretion, but its role in maintaining K+ homeostasis is often overlooked. For many years, passive diffusion and/or solvent drag were thought to be the primary mechanisms for K+ absorption in human and animal colon. However, it is now clear that apical H+ ,K+ -ATPase, in coordination with basolateral K+ -Cl- cotransport and/or K+ and Cl- channels operating in parallel, mediate electroneutral K+ absorption in animal colon. We now know that K+ absorption in rat colon reflects ouabain-sensitive and ouabain-insensitive apical H+ ,K+ -ATPase activities...
September 14, 2018: Comprehensive Physiology
Andrew Tinker, Qadeer Aziz, Yiwen Li, Mark Specterman
ATP sensitive potassium channels (KATP ) are so named because they open as cellular ATP levels fall. This leads to membrane hyperpolarization and thus links cellular metabolism to membrane excitability. They also respond to MgADP and are regulated by a number of cell signaling pathways. They have a rich and diverse pharmacology with a number of agents acting as specific inhibitors and activators. KATP channels are formed of pore-forming subunits, Kir6.1 and Kir6.2, and a large auxiliary subunit, the sulfonylurea receptor (SUR1, SUR2A, and SUR2B)...
September 14, 2018: Comprehensive Physiology
James G Tidball, Steven S Welc, Michelle Wehling-Henricks
The immune response to acute muscle damage is important for normal repair. However, in chronic diseases such as many muscular dystrophies, the immune response can amplify pathology and play a major role in determining disease severity. Muscular dystrophies are inheritable diseases that vary tremendously in severity, but share the progressive loss of muscle mass and function that can be debilitating and lethal. Mutations in diverse genes cause muscular dystrophy, including genes that encode proteins that maintain membrane strength, participate in membrane repair, or are components of the extracellular matrix or the nuclear envelope...
September 14, 2018: Comprehensive Physiology
Rodger A Liddle
Even the simplest animals possess sophisticated systems for sensing and securing nutrients. After all, ensuring adequate nutrition is essential for sustaining life. Once multicellular animals grew too large to be nourished by simple diffusion of nutrients from their environment, they required a digestive system for the absorption and digestion of food. The majority of cells in the digestive tract are enterocytes that are designed to absorb nutrients. However, the digestive tracts of animals ranging from worms to humans contain specialized cells that discriminate between nutrients and nondigestible ingestants...
June 18, 2018: Comprehensive Physiology
Nhung T Nguyen, Weidong Han, Wen-Ming Cao, Youjun Wang, Shufan Wen, Yun Huang, Minyong Li, Lupei Du, Yubin Zhou
The calcium release-activated calcium (CRAC) channel, composed of ORAI and stromal interaction molecules (STIM), represents a prototypical example of store-operated calcium entry in mammals. The ORAI-STIM signaling occurs at membrane contact sites formed by close appositions between the endoplasmic reticulum (ER) and the plasma membrane. ORAI1 is a four-pass transmembrane protein that forms a highly calcium-selective ion channel in the plasma membrane. STIM1 is an ER-resident, a single-pass transmembrane protein that serves as a calcium sensor within the ER lumen and a potent activator of ORAI1 calcium channels...
June 18, 2018: Comprehensive Physiology
David A Rubenstein, Wei Yin
This overview article for the Comprehensive Physiology collection is focused on detailing platelets, how platelets respond to various stimuli, how platelets interact with their external biochemical environment, and the role of platelets in physiological and pathological processes. Specifically, we will discuss the four major functions of platelets: activation, adhesion, aggregation, and inflammation. We will extend this discussion to include various mechanisms that can induce these functional changes and a discussion of some of the salient receptors that are responsible for platelets interacting with their external environment...
June 18, 2018: Comprehensive Physiology
Uwe Proske, Simon C Gandevia
The kinesthetic senses are the senses of position and movement of the body, senses we are aware of only on introspection. A method used to study kinesthesia is muscle vibration, which engages afferents of muscle spindles to trigger illusions of movement and changed position. When vibrating elbow flexors, it generates sensations of forearm extension, when vibrating extensors, sensations of forearm flexion. Vibrating the elbow joint produces no illusion. Vibrating flexors and extensors together at the same frequency also produces no illusion, because what is perceived is the signal difference between antagonist muscles of each arm and between arms...
June 18, 2018: Comprehensive Physiology
David O Bates, Nicholas Beazley-Long, Andrew V Benest, Xi Ye, Nikita Ved, Richard P Hulse, Shaney Barratt, Maria J Machado, Lucy F Donaldson, Steven J Harper, Maria Peiris-Pages, Domingo J Tortonese, Sebastian Oltean, Rebecca R Foster
The vascular endothelial growth factor (VEGF) family of proteins are key regulators of physiological systems. Originally linked with endothelial function, they have since become understood to be principal regulators of multiple tissues, both through their actions on vascular cells, but also through direct actions on other tissue types, including epithelial cells, neurons, and the immune system. The complexity of the five members of the gene family in terms of their different splice isoforms, differential translation, and specific localizations have enabled tissues to use these potent signaling molecules to control how they function to maintain their environment...
June 18, 2018: Comprehensive Physiology
Nati Hernando, Carsten A Wagner
States of hypo- and hyperphosphatemia have deleterious consequences including rickets/osteomalacia and renal/cardiovascular disease, respectively. Therefore, the maintenance of appropriate plasma levels of phosphate is an essential requirement for health. This control is executed by the collaborative action of intestine and kidney whose capacities to (re)absorb phosphate are regulated by a number of hormonal and metabolic factors, among them parathyroid hormone, fibroblast growth factor 23, 1,25(OH)2 vitamin D3 , and dietary phosphate...
June 18, 2018: Comprehensive Physiology
Han Fang, Robert L Judd
Adipose tissue is now recognized as an important endocrine organ, capable of secreting a large number of endocrine factors which regulate a wide variety of physiological functions. Adiponectin is one such factor, secreted in large quantities primarily from adipose tissue. Adiponectin is posttranslationally modified from a 30-kDa monomeric protein into different multimers (low molecular weight or trimer, middle molecular weight or hexamer, and high molecular weight) and secreted into the circulation. Upon binding to its receptors, AdipoR1 and R2, adiponectin initiates a series of tissue-dependent signal transduction events, including phosphorylation of adenosine monophosphate (AMPK) and p38 mitogen-activated protein kinase (p38 MAPK), and increased peroxisome proliferator-activated receptor alpha (PPARα) ligand activity...
June 18, 2018: Comprehensive Physiology
Medha Priyadarshini, Kumar U Kotlo, Pradeep K Dudeja, Brian T Layden
Nutrient sensing is a mechanism for organisms to sense their environment. In larger animals, including humans, the intestinal tract is a major site of nutrient sensing for the body, not surprisingly, as this is the central location where nutrients are absorbed. In the gut, bacterial fermentation results in generation of short chain fatty acids (SCFAs), a class of nutrients, which are sensed by specific membrane bound receptors, FFA2, FFA3, GPR109a, and Olfr78. These receptors are expressed uniquely throughout the gut and signal through distinct mechanisms...
June 18, 2018: Comprehensive Physiology
Patricia L Brubaker
Glucagon-like peptide-2 (GLP-2) is an intestinally derived hormone that enhances intestinal growth, digestion, absorption, barrier function, and blood flow in healthy animals as well as preventing damage and improving repair in preclinical models of enteritis and colitis and following massive small bowel resection. These beneficial effects of GLP-2 on the intestinal tract are largely recapitulated in humans with intestinal failure. The high-specificity of this peptide for the intestinal tract and the development of degradation-resistant, long-acting GLP-2 receptor agonists have rapidly led to clinical implementation of GLP-2-based therapy for the treatment of patients with short bowel syndrome, with few reported side effects...
June 18, 2018: Comprehensive Physiology
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