The role of brain somatostatin receptor 2 in the regulation of feeding and drinking behavior

Somatostatin was discovered four decades ago as hypothalamic factor inhibiting growth hormone release. Subsequently, somatostatin was found to be widely distributed throughout the brain and to exert pleiotropic actions via interaction with five somatostatin receptors (sst_1–5) that are also widely expressed throughout the brain. Interestingly, in contrast to the predominantly inhibitory actions of peripheral somatostatin, the activation of brain sst₂ signaling by intracerebroventricular injection of stable somatostatin agonists potently stimulates food intake and independently, drinking behavior in rodents. The orexigenic response involves downstream orexin-1, neuropeptide Y₁ and μ receptor signaling while the dipsogenic effect is mediated through the activation of the brain angiotensin 1 receptor. Brain sst₂ activation is part of mechanisms underlying the stimulation of feeding and more prominently water intake in the dark phase and is able to counteract the anorexic response to visceral stressors.     

A role for pancreatic polypeptide in feeding and body weight regulation

PP administration induces negative energy balance by suppressing food intake and gastric emptying while increasing energy expenditure in rodents. The mechanism of PP actions involves the changes in the expression of hypothalamic feeding-regulatory peptides and the activity of the vago-vagal and vago-sympathetic reflex arc. PP-overexpressing mice we developed exhibited the thin phenotype with decreased food intake and gastric emptying rate. Plasma cholecystokinin (CCK) concentrations were increased in the transgenic mice and CCK-1 receptor antagonist improved the anorexia of the animals. These results, together with the previous notion of PP as an anti-CCK hormone in pancreatic exocrine secretion and gallbladder contraction, indicate that PP-CCK interactions may be either antagonistic or synergistic and the transgenic mice may exhibit the mixed phenotype by overproduction of PP and CCK.     

Release of PYY from pig intestinal mucosa; luminal and neural regulation

The localization, molecular nature and secretion of Peptide YY (PYY), a putative gut hormone belonging to the Pancreatic Polypeptide family of peptides, was studied in pigs. Immunoreactive PYY was identified in a population of endocrine cells in the mucosal epithelium of the pig ileum. Release of PYY was observed in isolated perfused pig ileum in response to luminal stimulation with glucose and vascular administration of the neuropeptide gastrin-releasing peptide (GRP). Electrical stimulation of the vagus nerve supply to the distal small intestine in intact anaesthetized pigs resulted in release of PYY into the circulation. Stimulation of the splanchnic nerves did not affect the basal release of PYY. PYY-immunoreactivity extracted from ileal tissue or released to plasma or perfusate from the ileum was indistinguishable from synthetic porcine PYY by gel filtration and reverse phase HPLC. It is concluded that the secretion of PYY in the pig ileum may be regulated not only by nutritional luminal factors, but also by postsynaptic parasympathetic nerves.     

The role of cytoskeleton in glucose regulation

Cytoskeleton plays an important role in glucose regulation, mainly in the following three aspects. First, cytoskeleton regulates insulin secretion by guiding intracellular transport of insulin-containing vesicles and regulating release of insulin. Second, cytoskeleton is involved in insulin action by regulating distribution of insulin receptor substrate, GLUT4 translocation, and internalization of insulin receptor. In addition, cytoskeleton directs the intracellular distribution of glucose metabolism related enzymes including glycogen synthase and many glycolysis enzymes. Published in Russian in Biokhimiya, 2006, Vol. 71, No. 5, pp. 592–597.     

The role of mutants in metabolic regulation

Many Indian students of biochemistry and molecular biology do not appreciate the role of mutants in elucidation of metabolic pathways in general and metabolic regulation in particular. One reason is that a majority of biochemistry and enzymology textbooks used in India do not give adequate emphasis and importance to the role of biochemical genetics in unravelling metabolic pathways and their regulation. Teachers and students depend heavily on these textbooks. Many teachers pay little attention to the experimental strategies employed for the elucidation of metabolic/enzyme regulation. Asking specific questions about metabolic regulation, and requiring the students to read some important and key review articles for the answers could effectively rectify this malady.     

The role of information in cell regulation

The organised state of living cells must derive from information internal to the system; however, there are strong reasons, based on sound evidence, to reject the base sequence information encoded in the genomic DNA as being directly relevant to the regulation of cellular phenotype. Rather, it is argued here that highly specific relational information, encoded on the gene products, mainly proteins, is responsible for phenotype. This regulatory information emerges as the peptide folds into a tertiary structure in much the same way as enzymic activity emerges under the same circumstances. The DNA coding sequence serves as a “data base” in which a second category of relational information is stored to enable accurate reproduction of the cellular peptides. In the context of the cell, therefore, information is physical in character and contributes, through its ability to dissipate free energy, to the maximisation of the entropy of the cell according to the 2nd law of thermodynamics.     

The role of stress in colicin regulation

Bacteriocins produced by Enterobacteriaceae are high molecular weight toxic proteins that kill target cells through a variety of mechanisms, including pore formation and nucleic acid degradation. What is remarkable about these toxins is that their expression results in death to the producing cells and therefore bacteriocin induction have to be tightly regulated, often confined to times of stress. Information on the regulation of bacteriocins produced by enteric bacteria is sketchy as their expression has only been elucidated in a handful of bacteria. Here, we review the known regulatory mechanisms of enteric bacteriocins and explore the expression of 12 of them in response to various triggers: DNA-damaging agents, stringent response, catabolite repression, oxidative stress, growth phase, osmolarity, cold shock, nutrient deprivation, anaerobiosis and pH stress. Our results indicate that the expression of bacteriocins is mostly confined to mutagenic triggers, while all other triggers tested are limited inducers.     

The role of dynamics in allosteric regulation

The biomolecular conformational changes often associated with allostery are, by definition, dynamic processes. Recent publications have disclosed the role of pre-existing equilibria of conformational substates in this process. In addition, the role of dynamics as an entropic carrier of free energy of allostery has been investigated. Recent work thus shows that dynamics is pivotal to allostery, and that it constitutes much more than just the move from the 'T'-state to the 'R'-state. Emerging computational studies have described the actual pathways of allosteric change.     

The role of feeding rejection in Drosophila mutation assays

The frequencies of sex-linked recessive lethal mutations recovered in the male post-meiotic germ cells of Drosophila after feeding on solutions containing a mutagen (either 1 mM methyl methanesulfonate, MMS or 2 mM ethyl methanesulfonate, EMS) and 5-bromo-2-deoxyuridine (BUdR) were significantly lower than the frequencies observed after treatment with the mutagen alone. In an attempt to explain the apparent 'protective' effect of BUdR, the feeding behavior of the flies was monitored for differences in the uptake of the mutagen-containing solution in the presence and absence of BUdR. This was accomplished by measuring the uptake of [14C]sucrose. The results indicated that the uptake of the feeding solution is inhibited by the presence of the selected concentration of BUdR (1.0 or 32.5 mM). Such a reduced uptake of the mutagen could alone account for the reduction in mutational yields noticed in treatments containing mutagen + BUdR compared to the ones with the mutagen alone. These results emphasize the need to monitor the feeding behavior of flies in experiments involving adult feeding.     

The role of the daily feeding rhythm in the regulation of the day/night rhythm in triglyceride secretion in rats

Plasma triglyceride (TG) levels show a clear daily rhythm, however, thus far it is still unknown whether this rhythm results from a daily rhythm in TG production, TG uptake or both. Previous studies have shown that feeding activity affects plasma TG concentrations, but it is not clear how the daily rhythm in feeding activity affects plasma TG concentrations. In the present study, we measured plasma TG concentrations and TG secretion rates in rats at 6 Zeitgeber times to investigate whether plasma TG concentrations and TG secretion show a daily rhythm. We found that plasma TG concentrations and TG secretion show a significant day/night rhythm. Next, we removed the daily rhythm in feeding behavior by introducing a 6-meals-a-day (6M) feeding schedule to investigate whether the daily rhythm in feeding behavior is necessary to maintain the daily rhythm in TG secretion. We found that the day/night rhythm in TG secretion was abolished under 6M feeding conditions. Hepatic apolipoprotein B (ApoB) and microsomal TG transfer protein (Mttp), which are both involved in TG secretion, also lost their daily rhythmicity under 6M feeding conditions. Together, these results indicate that: (1) the daily rhythm in TG secretion contributes to the formation of a day/night rhythm in plasma TG levels and (2) a daily feeding rhythm is essential for maintaining the daily rhythm in TG secretion.     

The regulation of feeding in Locusta migratoria: Internal inhibitory mechanisms

During the course of a meal by insects with an empty gut, food is held in the foregut and the midgut remains empty. The last part of the foregut to fill is the extreme anterior end of the crop, and stretch receptors in this region control the amount eaten. Cutting the posterior pharyngeal nerves isolates these receptors from the frontal garglion and results in hyperphagia pharyngeal nerves isolates these receptors from the frontal garglion and results in hyperphagia during one meal. On unfavourable food, when smaller amounts are eaten, distension of the foregut is not involved in regulating meal size.Feedback from receptors in the body wall is not important in regulating meal size; most of the increase in gut volume resulting from feeding is taken up by the collapse of the air sacs so that there is little or no change in the body volume.

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Zusammenfassung Alle Hauptnerven des Mund- und Rachennervensystems wurden kontrolliert reseziert. Erst wenn die rückwärtigen Rachennerven zerschnitten werden, nehmen die Insekten wesentlich mehr Nahrung zu sich. Solche Insekten versuchen längere Zeit zu fressen.Wenn sich während des Fressens der Vorderdarm füllt, wird keine Nahrung an den Mitteldarm weitergegeben und sein Vorderende ist der letzte Teil, der sich vollständig ausdehnt. Nach Durchtrennung der rückwärtigen Rachennerven sind alle Teile des Vorderdarms offen-sichtlich mehr gedehnt. Eine solche erhöhte Nahrungsaufnahme tritt aber nicht ein, wenn die Nahrung relativ ungünstig ist. Das Abbinden des Kropfes verursacht beim nachträglichen Fressen keine übermäßige Ausdehnung des Vorderteiles.Die Nahrungsaufnahme hat keinen Unterschied im Körpervolumen zur Folge und das Durchtrennen des ventralen Nervenstranges bleibt ohne Einfluß auf die nachträglich aufgenommenen Nahrungsmengen. Das vergrößerte Darmvolumen wird durch Kollaps des Luftsackes kompensiert.

     

Enhancement of feeding suppression by PYY(3-36) in rats with area postrema ablations

We investigated suppression of food intake by intraperitoneal (IP) injections of peptide YY(3-36) (PYY(3-36)) (24, 60, or 150 microg/kg) in rats with ablations of the area postrema (APX) and in controls with sham ablations. In controls, PYY(3-36)-induced suppression was modest and short-lived, averaging 20% at most and persisting less than 6h. The highest dose tested (150 microg/kg) was even less effective than were the two lesser doses after 3h. APX did not diminish the potency of these effects of PYY(3-36). In fact, the magnitude of suppression produced by the greatest dose of PYY(3-36) in APX rats was significantly greater than in controls and PYY(3-36)-induced suppression was still present at 24h.     

益生菌在血糖调控中的作用

随着经济及生活水平的提高，营养过剩导致营养代谢疾病中2型糖尿病（type 2 diabetes mellitus，T2DM）发生率骤增。患者血糖升高及并发症严重降低生活质量，增加经济负担。现行降糖药存在局限性和副作用，而益生菌具有安全、经济和有效等特点，并且能够降血糖和减轻并发症等。益生菌在糖尿病预防、治疗和重塑肠道微生态健康方面具有良好的应用前景，逐渐成为糖尿病防治的研究热点。虽然益生菌有望攻克糖尿病，但是调控血糖的机制需要更加深入的研究。本文综述了益生菌调控血糖的应用及机制研究、发展趋势与前景及挑战，为调控血糖微生态制剂的开发提供理论基础。     

肠道菌群在机体免疫调节功能中的作用

肠道菌群被称为是人体的一个重要"器官",具有数量庞大、种类繁多等特点,对人体具有重要的生理与病理意义。肠道菌群对机体免疫功能的影响日益受到广泛关注。本文主要就肠道菌群对肠道形态及功能、肠道黏膜免疫系统以及肠道外免疫系统三个方面的影响进行综述。     

The role of atypical ubiquitination in cell regulation

Ubiquitination is a type of intracellular proteins post-translational modification (PTM) characterized by covalent attachment of ubiquitin molecules to target proteins. This includes monoubiquitination (attachment of one ubiquitin molecule), multiple monoubiquitination also known as multiubiquitination (attachment of several monomeric ubiquitin molecules to a target protein), and polyubiquitination (attachment of ubiquitin chains consisting of several, most frequently four ubiquitin monomers to a target protein). In the case of polyubiquitination, linear or branched polyubiquitin chains are formed. Their formation involves various lysine residues of monomeric ubiquitin. The best studied is Lys48-linked polyubiquitination, which targets proteins for proteasomal degradation. In this review we have considered examples of so-called atypical polyubiquitination, which mainly involves other lysine residues (Lys6, Lys11, Lys27, Lys29, Lys33, Lys63) and also N-terminal methionine. The considered examples convincingly demonstrate that polyubiquitination of proteins (not necessarily) targets proteins for their proteolytic degradation in proteasomes. Atypically polyubiquitinated proteins are involved in regulation of various processes including immune response, genome stability, signal transduction, etc. Alterations of ubiquitination machinery is crucial for development of serious diseases.