Cortisol is the principal corticosteriod in teleost fishes and its plasma concentrations rise dramatically during stress. The relationship between this cortisol increase and its metabolic consequences are subject to extensive debate. Much of this debate arises from the different responses of the many species used, the diversity of approaches to manipulate cortisol levels, and the sampling techniques and duration. Given the extreme differences in experimental approach, it is not surprising that inconsistencies exist within the literature. This review attempts to delineate common themes on the physiological and metabolic roles of cortisol in teleost fishes and to suggest new approaches that might overcome some of the inconsistencies on the role of this multifaceted hormone. We detail the dynamics of cortisol, especially the exogenous and endogenous factors modulating production, clearance and tissue availability of the hormone. We focus on the mechanisms of action, the biochemical and physiological impact, and the interaction with other hormones so as to provide a conceptual framework for cortisol under resting and/or stressed states. Interpretation of interactions between cortisol and other glucoregulatory hormones is hampered by the absence of adequate hormone quantification, resulting in correlative rather than causal relationships.

Cortisol in teleosts: dynamics, mechanisms of action, and metabolic regulation

Mammalian skeletal muscle comprises different fiber types, whose identity is first established during embryonic development by intrinsic myogenic control mechanisms and is later modulated by neural and hormonal factors. The relative proportion of the different fiber types varies strikingly between species, and in humans shows significant variability between individuals. Myosin heavy chain isoforms, whose complete inventory and expression pattern are now available, provide a useful marker for fiber types, both for the four major forms present in trunk and limb muscles and the minor forms present in head and neck muscles. However, muscle fiber diversity involves all functional muscle cell compartments, including membrane excitation, excitation-contraction coupling, contractile machinery, cytoskeleton scaffold, and energy supply systems. Variations within each compartment are limited by the need of matching fiber type properties between different compartments. Nerve activity is a major control mechanism of the fiber type profile, and multiple signaling pathways are implicated in activity-dependent changes of muscle fibers. The characterization of these pathways is raising increasing interest in clinical medicine, given the potentially beneficial effects of muscle fiber type switching in the prevention and treatment of metabolic diseases.

Fiber types in mammalian skeletal muscles.

The ability to adapt to altered availability of free water is a fundamental property of living cells. The principles underlying osmoadaptation are well conserved. The yeast Saccharomyces cerevisiae is an excellent model system with which to study the molecular biology and physiology of osmoadaptation. Upon a shift to high osmolarity, yeast cells rapidly stimulate a mitogen-activated protein (MAP) kinase cascade, the high-osmolarity glycerol (HOG) pathway, which orchestrates part of the transcriptional response. The dynamic operation of the HOG pathway has been well studied, and similar osmosensing pathways exist in other eukaryotes. Protein kinase A, which seems to mediate a response to diverse stress conditions, is also involved in the transcriptional response program. Expression changes after a shift to high osmolarity aim at adjusting metabolism and the production of cellular protectants. Accumulation of the osmolyte glycerol, which is also controlled by altering transmembrane glycerol transport, is of central importance. Upon a shift from high to low osmolarity, yeast cells stimulate a different MAP kinase cascade, the cell integrity pathway. The transcriptional program upon hypo-osmotic shock seems to aim at adjusting cell surface properties. Rapid export of glycerol is an important event in adaptation to low osmolarity. Osmoadaptation, adjustment of cell surface properties, and the control of cell morphogenesis, growth, and proliferation are highly coordinated processes. The Skn7p response regulator may be involved in coordinating these events. An integrated understanding of osmoadaptation requires not only knowledge of the function of many uncharacterized genes but also further insight into the time line of events, their interdependence, their dynamics, and their spatial organization as well as the importance of subtle effects.

Osmotic Stress Signaling and Osmoadaptation in Yeasts

Adenosine is a modulator that has a pervasive and generally inhibitory effect on neuronal activity. Tonic activation of adenosine receptors by adenosine that is normally present in the extracellular space in brain tissue leads to inhibitory effects that appear to be mediated by both adenosine A1 and A2A receptors. Relief from this tonic inhibition by receptor antagonists such as caffeine accounts for the excitatory actions of these agents. Characterization of the effects of adenosine receptor agonists and antagonists has led to numerous hypotheses concerning the role of this nucleoside. Previous work has established a role for adenosine in a diverse array of neural phenomena, which include regulation of sleep and the level of arousal, neuroprotection, regulation of seizure susceptibility, locomotor effects, analgesia, mediation of the effects of ethanol, and chronic drug use.

The Role and Regulation of Adenosine in the Central Nervous System

Glycogen synthase kinase 3 (GSK3) was initially described as a key enzyme involved in glycogen metabolism, but is now known to regulate a diverse array of cell functions. The study of the substrate specificity and regulation of GSK3 activity has been important in the quest for therapeutic intervention.

The renaissance of GSK3.

α-Glucosidase deficiency in generalized glycogen-storage disease (Pompe's disease)

Pyrophosphate : fructose-6-phosphate phosphotransferase (PPi-PFK) has been purified 150-fold from potato tubers and the kinetic properties of the purified enzyme have been investigated both in the forward and the reverse direction. Saturation curves for fructose 6-phosphate and also for fructose 1,6-bisphosphate were sigmoidal whereas those for PPi and Pi were hyperbolic. In the presence of fructose 2,6-bisphosphate, the affinity for fructose 6-phosphate and for fructose 1,6-bisphosphate were greatly increased and the kinetics became Michaelian. The effect of fructose 2,6-bisphosphate was increased by the presence of fructose 6-phosphate and decreased by the presence of Pi. Consequently, the Ka for fructose 2,6-bisphosphate was as low as 5 nM for the forward reaction and reached 150 nM for the reverse reaction. On the basis of these properties, a procedure allowing one to measure fructose 2,6-bisphosphate in amounts lower than a picomole, is described.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1982.tb07039.x

A kinetic study of pyrophosphate: fructose-6-phosphate phosphotransferase from potato tubers. Application to a microassay of fructose 2,6-bisphosphate.

PERSPECTIVES AND SUMMARy 618 GENERAL PROPERTIES OF GLUCONEOGENESIS AND GLYCOLYSIS IN THE LIVER 619 Gluconeogenesis 619 Glycolysis 619 Control Steps 620 ENZYME PROPERTIES 620 Pyruvate Carboxylase and Other Mitochondrial Involvement 620 Phosphoenolpyruvate Carboxykinase 623 Pyruvate Kinase 625 Fructose 1,6-Bisphosphatase 626 Fructose 2,6-Bisphosphatase 629 6-Phosphofructokinases 629 Glucose 6-Phosphatase 633 Glucokinase 634 THE CONTROL OF METABOLIC FLUX BY HORMONES AND OTHER EFFECTORS ...... 634 Cyclic AMP, Glucagon, and f3-Adrenergic Agents 634 Fructose 2,6-Bisphosphate 639 ex-Adrenergic Agents, Vasopressin, and Angiotensin 641 Glucocorticoids 643 Glucose 643 THE FUTILE CYCLES 644 Glucose/Glucose 6-Phosphate Cycle 644 Fructose 6-Phosphate/Fructose 1,6-Bisphosphate Cycle 646 Pyruvate/Phosphoenolpyruvate Cycle 647

Gluconeogenesis and Related Aspects of Glycolysis

It was in 1909 that Young, in the laboratory of Harden, isolated from fermenting yeast the fructose bisphosphate (the Harden and Young ester) that was later identified by Levene & Raymond (1928) as fructose 1,6-bisphosphate. Some 71 years elapsed until a second fructose bisphosphate was isolated from living cells and identified as fructose 2,6bisphosphate (Van Schaftingen et al., 1980c). In contrast with its elder brother, Fru-2,6-P2 is not an intermediary metabolite of glycolysis, but its most potent regulator. In the present review, we will summarize the work that led to its discovery and we will try to delineate its potential role in the control of metabolism in various organisms.

/pdf/fructose-2-6-bisphosphate-2-years-after-its-discovery-12bwfad1ea.pdf

Fructose 2,6-bisphosphate 2 Years After its Discovery

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2870%2980569-5

Henri-Géry Hers

Papers

α-Glucosidase deficiency in generalized glycogen-storage disease (Pompe's disease)

A kinetic study of pyrophosphate: fructose-6-phosphate phosphotransferase from potato tubers. Application to a microassay of fructose 2,6-bisphosphate.

Gluconeogenesis and Related Aspects of Glycolysis

Fructose 2,6-bisphosphate 2 Years After its Discovery

The control of glycogen metabolism in the liver.