L-arginine and pancreatic islet blood flow in anesthetized rats

The aim of the present study was to see if L-arginine, which induces insulin release and is a precursor of the endothelial-derived relaxing factor nitric oxide, affects whole pancreatic and/or islet blood flow. For this purpose, anesthetized male Sprague-Dawley rats were injected intravenously with either saline or L-arginine (25, 100 or 250 mg/kg body weight). All doses of arginine caused a slight increase in blood glucose concentration, while the highest dose (250 mg/kg body weight) also increased insulin concentration. However, no changes in either mean arterial blood pressure, whole pancreatic or islet blood flow could be discerned with any of the doses of arginine used. It is concluded that insulin release is not necessarily associated with an increased islet blood perfusion.     

The role of phosphoenolpyruvate in insulin secretion: the effect of L-phenylalanine

Summary Incubation of rat islets with phenylalanine increased the tissue content of phosophoenolpyruvate, both in the presence and in the absence of glucose. At the same time, L-phenylalanine neither stimulated nor inhibited insulin release. It is unlikely that insulin secretion is tightly coupled to the availability of phosphoenolpyruvate in rat islets.     

Factors influencing the intestinal phase of pancreatic exocrine secretion in the turkey

The present study was done to investigate the factors regulating the intestinal phase of exocrine pancreatic secretion in the turkey. The intestine of turkeys equipped with pancreatic fistulas was perfused with peptone solution, fat emulsion and hydrochloric acid (HCl), and pancreatic flow and protein output were measured. Neither peptone solution nor fat emulsion had any effects on pancreatic secretion. HCl enhanced the flow rate of pancreatic juice but not protein output. To clarify the neural mechanism of this phenomenon, the vagal postganglionic blocker atropine was continuously infused and pancreatic secretion in response to intestinal HCl was measured. Atropine completely suppressed both pancreatic flow and protein output. It is suggested that the avian intestinal phase of pancreatic secretion is mainly controlled by cholinergic action though HCl stimulation.     

Testosterone secretion by Mongolian gerbil interstitial cells during short-term incubation depends on androgen precursors and serum proteins but not on gonadotrophins

Summary Interstitial cells from the testes of the Mongolian gerbil have been used to investigate the effects of serum proteins on testosterone production stimulated by hCG and steroidal precursors. Short-term incubation of interstitial cells with progesterone or DHEA resulted in a rapid increase of testosterone secretion; this effect was even more pronounced in the presence of calf serum. On the other hand, addition of hCG (10 mIU) had no significant effect on testosterone release during the 30-min incubation. These results demonstrate that the magnitude of the steroidogenic response of short-term incubated interstitial cells is a complex function, mainly of precursor concentrations and binding capacities of serum proteins but not of gonadotrophins.8 October 1986     

Dysfunctional insulin secretion in type 2 diabetes: role of metabolic abnormalities

Insulin secretion is finely tuned to the requirements of tissues by tight coupling to prevailing blood glucose levels. The normal regulation of insulin secretion is coupled to glucose metabolism in the pancreatic B cell, a major but not exclusive signal for secretion being closure of K⁺ATP (adenosine triphosphate)-dependent channels in the cell membrane through an increase in cytosolic ATP/adenosine diphosphate. Insulin secretion in type 2 diabetes is abnormal in several respects due to genetic causes but also due to the metabolic environment of the pancreatic B cells. This environment may be particularly important for the deterioration of insulin secretion which occurs with increasing duration of diabetes. Factors in the environment with potential importance include overstimulation, a negative effect of hyperglycemia per se (‘glucotoxicity’) as well as adverse effects of elevated fatty acids (‘lipotoxicity’). Elucidating the mechanisms behind these factors as well as their clinical importance will pave the way for treatment which could preserve B-cell function in type 2 diabetic patients. Received 4 October 1999; received after revision 1 November 1999; accepted 3 December 1999     

Lipid peroxidation,low-level chemiluminescence and regulation of secretion in the mammary gland

In mammary explants of lactating mice, changes in the intensity of chemiluminescence (CL) were observed after the addition to the incubation medium of hormones and mediators that are involved in the regulation of secretion: oxytocin, acetylcholine, epinephrine and norepinephrine. A 15-min period of treatment with oxytocin, epinephrine or norepinephrine changed the level of thiobarbituric acid-reactive substances (TBARS). Two mammary explants, one of which was treated with oxytocin, acetylcholine, epinephrine or norepinephrine, were found to interact even when separated by a quartz glass wall. Analysis of the level of TBARS formation in these two explants showed that the observed interactions might be connected with light emission resulting from lipid peroxidation (LP) processes. The possible role of LP and low-level CL in the regulation of mammary gland secretion is discussed.     

The role of perireceptor events in vertebrate olfaction

The perception of odours and pheromones is mediated by small soluble carrier proteins that belong to the family of lipocalins. Those secreted by the nasal mucosa are called odorant-binding proteins (OBPs) for their binding activity towards volatile compounds. Proteins of similar structure, which we call pheromone-binding proteins (PBPs), help to deliver volatile pheromones in the environment. They are present in high concentration in biological fluids, such as urine, saliva and vaginal discharge, involved in chemical communication between conspecifics. Several subclasses of OBPs have been identified in the same animal species, each best related to a particular group of PBPs. Such similarities, together with anatomical and behavioural evidence, suggest that OBPs may be involved in the perception of pheromones.     

Significance of ionic fluxes and changes in membrane potential for stimulus-secretion coupling in pancreatic B-cells

Conclusions This brief review has tried to shed some light on the mechanisms and significance of the changes in membrane potential and in ionic fluxes occurring in B-cells upon glucose stimulation. There is now strong evidence that, under physiological conditions at least, these electrical events-and the underlying modifications of ionic permeabilities and fluxes — play a causal role in the stimulation of insulin release. It also seems clear that certain accompanying ionic fluxes have no direct stimulatory role, but may be important in maintaining cellular homeostasis. Recent experimental evidence has also shown that the electrical activity in B-cells is not an all-or-none stereotypic response. Not only can its intensity be adjusted to the magnitude of the stimulus, but its characteristics can also be modulated by potentiators Our knowledge of the stimulus-secretion coupling has markedly progressed over the past few years, but elucidation of several important steps remains a challenging goal. There is no doubt that parallel measurements of insulin release, of ionic fluxes and of membrane potential in B-cells will still contribute to that understanding.     

The role of proteolytic processing in the morphogenesis of virus particles

Proteinases are encoded by many RNA viruses, all retroviruses and several DNA viruses. They play essential roles at various stages in viral replication, including the coordinated assembly and maturation of virions. Most of these enzymes belong to one of three (Ser, Cys or Asp) of the four major classes of proteinases, and have highly substrate-selective and cleavage specific activities. They can be thought of as playing one of two general roles in viral morphogenesis. Structural proteins are encoded by retroviruses and many RNA viruses as part of large polyproteins. Their proteolytic release is a prerequisite to particle assembly; consequent structural rearrangement of the capsid domains serves to regulate and direct association and assembly of capsid subunits. The second general role of proteolysis is in assembly-dependent maturation of virus particles, which is accompanied by the acquisition of infectivity.     

The role of growth hormone and insulin-like growth factors in the immune system

Growth hormone (GH) and insulin-like growth factor I (IGF-I) can modulate the development and function of the immune system. In this chapter, we present data on the expression of receptors for GH and IGFs and the in vitro and in vivo effects of these proteins. We show that expression of GH and IGFs in the immune system opens up the possibility that these proteins are not only involved in endocrine control of the immune system but can also play a role as local growth and differentiation factors (cytokines). Endocrine control of GH could be direct or mediated via endocrine or autocrine/paracrine IGF-I. In addition, GH can act as an autocrine or paracrine factor itself. Furthermore, IGF-I in the immune system has been shown to be regulated by cytokines, such as interleukin-1 and interferon-γ, alluding to a cytokine-like function of IGF-I. In addition to data on the function of GH and IGF-I in the immune system, we present new findings which imply a possible function of IGF-II and IGF-binding proteins.     

The balance between immunity and tolerance: The role of Langerhans cells

Langerhans cells are immature skin-homing dendritic cells that furnish the epidermis with an immune surveillance system, and translate information between the internal and external milieu. Dendritic cells, in particular Langerhans cells, are gaining prominence as one of the potential principal players orchestrating the decision between immunity and tolerance. Langerhans cells capture aberrant self-antigen and pathogen-derived antigen for display to the efferent immune response. Recent evidence suggests redundancy in the antigen-presenting function of Langerhans cells, with dermal dendritic subsets capable of fulfilling an analogous role. There is mounting evidence that Langerhans cells can cross-prime T cells to recognize antigens. Langerhans cells are proposed to stimulate T regulatory cells, and are implicated in the pathogenesis of cutaneous T cell lymphoma.The phenotype of Langerhans cells, which may be tolerogenic or immunogenic, appears to depend on their state of maturity, inciting immunogen and cytokine environment, offering the potential for manipulation in immunotherapy. Received 6 August 2008; received after revision 18 September 2008; accepted 13 October 2008     

The effects of ethanol on embryonic actin: A possible role in teratogenesis

Summary When the neural crest is cultured in the long or short term presence of ethanol, monoclonal anti-actin reveals the development of a disorganized actin cytoskeleton. In the long term, many cells fail to differentiate morphologically, whereas in the short term already differentiated cells rapidly alter their shape and their cell-to-cell contacts.     

The role of the autonomic nervous system in mediating pancreatic endocrine responses to arginine in the calf

Summary The release of insulin which occurred in response to arginine, in the conscious calf, differed from that which occurs in response to glucose in that it was not significantly affected by either adrenergic or muscarinic blocking agents. Release of pancreatic glucagon was reduced by pretreatment with phentolamine.This work was supported by the British Diabetic Association. It is a particular pleasure to acknowledge the skilled assistance provided by Messrs P. M. M. Bircham and G. P. McGregor.     

The innate immunity of the central nervous system in chronic pain: The role of Toll-like receptors

Toll-like receptors (TLRs) are a family of pattern recognition receptors that mediate innate immune responses to stimuli from pathogens or endogenous signals. Under various pathological conditions, the central nervous system (CNS) mounts a well-organized innate immune response, in which glial cells, in particular microglia, are activated. Further, the innate immune system has emerged as a promising target for therapeutic control of development and persistence of chronic pain. Especially, microglial cells respond to peripheral and central infection, injury, and other stressor signals arriving at the CNS and initiate a CNS immune activation that might contribute to chronic pain facilitation. In the orchestration of this limited immune reaction, TLRs on microglia appear to be most relevant in triggering and tailoring microglial activation, which might be a driving force of chronic pain. New therapeutic approaches targeting the CNS innate immune system may achieve the essential pharmacological control of chronic pain. Received 21 November 2006; received after revision 8 January 2007; accepted 7 February 2007     

The role of key residues in structure, function, and stability of cytochrome-c

Cytochrome-c (cyt-c), a multi-functional protein, plays a significant role in the electron transport chain, and thus is indispensable in the energy-production process. Besides being an important component in apoptosis, it detoxifies reactive oxygen species. Two hundred and eighty-five complete amino acid sequences of cyt-c from different species are known. Sequence analysis suggests that the number of amino acid residues in most mitochondrial cyts-c is in the range 104?±?10, and amino acid residues at only few positions are highly conserved throughout evolution. These highly conserved residues are Cys14, Cys17, His18, Gly29, Pro30, Gly41, Asn52, Trp59, Tyr67, Leu68, Pro71, Pro76, Thr78, Met80, and Phe82. These are also known as “key residues”, which contribute significantly to the structure, function, folding, and stability of cyt-c. The three-dimensional structure of cyt-c from ten eukaryotic species have been determined using X-ray diffraction studies. Structure analysis suggests that the tertiary structure of cyt-c is almost preserved along the evolutionary scale. Furthermore, residues of N/C-terminal helices Gly6, Phe10, Leu94, and Tyr97 interact with each other in a specific manner, forming an evolutionary conserved interface. To understand the role of evolutionary conserved residues on structure, stability, and function, numerous studies have been performed in which these residues were substituted with different amino acids. In these studies, structure deals with the effect of mutation on secondary and tertiary structure measured by spectroscopic techniques; stability deals with the effect of mutation on T _m (midpoint of heat denaturation), ?G _D (Gibbs free energy change on denaturation) and folding; and function deals with the effect of mutation on electron transport, apoptosis, cell growth, and protein expression. In this review, we have compiled all these studies at one place. This compilation will be useful to biochemists and biophysicists interested in understanding the importance of conservation of certain residues throughout the evolution in preserving the structure, function, and stability in proteins.     

Clinical aspects of the melatonin action: impact of development,aging, and puberty,involvement of melatonin in psychiatric disease and importance of neuroimmunoendocrine interactions

During the last decade we have learned much on physiological changes in the secretion of the pineal hormone melatonin (MLT) in man. Reportedly, there is little or no MLT secreted before age 3 months. Then MLT production commences, becmes circadian, and reaches highest nocturnal levels at the age of 1–3 years. During all of childhood nocturnal peak levles drop progressively by 80% until adult levels are reached. This alteration appears to be the consequence of increasing body size in face of constant MLT production during childhood. The biological significance of this MLT alteration is presently unknown. Because of conceptual considerations, major depressive syndrome (MDS) and seasonal affective disorder (SAD) have been in the focus of pineal research for several years. Although in these disorders alterations in MLT levels could not be substantiated, light therapy, a consequence of this research, was discovered as an effective treatment for SAD and perhaps for MDS. In addition, there is some recent evidence for low MLT levels in schizophrenia. Finally, the potential effect of MLT in neuroimmunoendocrine interactions is presently explored. Reportedly, in vitro studies and animal experiments give evidence for a modulatory role of MLT in the immune response. However, the exact way of this possible action of MLT remains to be clarified. Clinical studies are too scant for a meaningful estimation of MLT's involvement in human neuroimmunoendocrine interactions.     

In vitro biosynthesis of juvenile hormone III by the corpora allata ofCalliphora vomitoria and its role in ovarian maturation and sexual receptivity

Summary JH III is the only JH detected by GLC-MS in medium from in vitro incubations of corpora allata of adult females ofCalliphora vomitoria. When corpora allata were removed from females at various times during the reproductive cycle and the JH III produced by the glands in vitro measured by a JH III radioimmunoassay, an increase in the level of synthesis was found to occur before previtellogenesis (0–24 h). A second increase appeared at the onset of vitellogenesis (72–83 h) and continued until the end of vitellogenesis (96 h) and the occurrence of chorionation (120 h). Since sexual receptivity develops with vitellogenesis, the significantly higher levels of JH III biosynthesis in vitro at this time supports a possible role for JH in the acquisitive of receptivity.