Pancreatic glucagon fails to inhibit sham feeding in the rat

Rats were equipped with chronic gastric cannulas, and the effects of intraperitoneal injections of pancreatic glucagon on sham feeding, with cannulas open, and real feeding, with cannulas closed, were compared. Glucagon (100–2,500 μg/kg) suppressed cumulative food intake during real feeding tests 9–33%, but had no effect during sham feeding. Despite their increased food intakes, sham feeding rats took discrete meals terminated by the behavioral satiety sequence. In addition to not affecting total intake, glucagon failed to affect meal size, latency to rest, or intermeal interval during sham feeding. To investigate the possiblity that glucagon did not inhibit sham feeding because it did not elicit hyperglycemia, we measured hepatic vein blood glucose after glucagon injections in sham feeding rats: glucagon elicited marked hyperglycemia during sham feeding. Therefore, the absence of glucagon's satiety effect in sham feeding is not due to the lack of hepatic glycogenolysis and hyperglycemia. These results suggest that some mechanism other than hyperglycemia which normally accompanies food ingestion is necessary for glucagon to have a satiety effect.     

Metabolic adaptations of liver mitochondria during restricted feeding schedules

Food anticipatory activity (FAA) is an output of the food-entrained oscillator (FEO), a conspicuous biological clock that expresses when experimental animals are under a restricted food schedule (RFS). We have shown that the liver is entrained by RFS and exhibits an anticipatory response before meal time in its oxidative and energetic state. The present study was designed to determine the mitochondrial oxidative and phosphorylating capacity in the liver of rats under RFS to further support the biochemical anticipatory role that this organ plays during the food entrainment (9). Metabolic and functional parameters of liver mitochondria were characterized before (0800 h), during (1100 h), and after (1400 h) FAA. The main results were as follows. First, there was an enhancement during FAA (1100 h) in 1) oxidative capacity (site I of the electron transport chain), 2) phosphorylating ability (estimated by ATP synthesis), and 3) activities of NADH shuttles. Second, after rats were fed (1400 h), the phosphorylating capacity remained high, but this was not the case for the respiratory control ratio for site I. Finally, in the three experimental conditions before, during, and after FAA, an increment was detected in the H(+) electrochemical potential, due to an elevation in mitochondrial membrane potential, and in mitochondrial yield. Most of the changes in mitochondrial properties related to RFS were also present when results were compared with those from the 24-h fasted group. In conclusion, the results support the notion that a distinctive rheostatic state is installed in the metabolic activity of the liver when FEO is being expressed.     

Effect of atropine on plasma gastrin and somatostatin concentrations during sham feeding in man

The purpose of these studies was to measure circulating gastrin and somatostatin concentrations during sham feeding in humans and to evaluate the effect of two doses of intravenous atropine on circulating concentrations of these peptides. Gastric acid and bicarbonate secretion and pulse rate were also measured. Sham feeding increased plasma gastrin concentrations by approximately 15 pg/ml but had no effect on plasma somatostatin-like immunoreactivity (SLI). A small dose of atropine (5 micrograms/kg) augmented plasma gastrin concentrations during sham feeding significantly (P less than 0.01), but did not affect plasma SLI. Atropine also significantly inhibited gastric acid secretion and gastric bicarbonate secretion (by 62% and 52%, respectively), but pulse rate was not affected. A larger dose of atropine (15 micrograms/kg intravenously) suppressed plasma gastrin concentrations significantly compared to the smaller 5 micrograms/kg atropine dose (P less than 0.02), so that plasma gastrin concentrations when 15 micrograms/kg atropine was given were not significantly different from those during the control study. 15 micrograms/kg atropine reduced gastric acid and bicarbonate secretion by 81% and 66%, respectively, and also increased pulse rate by 15 min-1. These studies indicate that small doses of atropine enhance vagally mediated gastrin release in humans, probably by blocking a cholinergic inhibitory pathway for gastrin release. Although the nature of this cholinergic inhibitory mechanism is unclear, we found no evidence to incriminate somatostatin. Our finding that the larger dose of atropine reduced serum gastrin concentrations compared with the smaller dose suggests that certain vagal-cholinergic pathways may facilitate gastrin release.     

Gastric lipase and pepsinogen during the ontogenesis of rabbit gastric glands

In rabbit stomach, gastric lipase activity level was found to increase from birth to 30 days old (weaning), and then decreased. In contrast, pepsin activity only appeared between 30 to 45 days old, and increased till to the adult level. It was observed that maturation of gastric glands in cardial mucosa was a downward elongation process from the mitotic cell pool. These mitotic cells were always found in the neck of the gastric glands, corresponding to the bottom of the gland at 6 days old and to the mid-zone of the gland in adult. Location of rabbit gastric lipase (RGL) cells in cardial glands varied with age and was found along the pit of the gastric glands at 6 days old. The extent of this cellular location decreased with age, whereas a second RGL cell zone appeared below the mitotic cell area at 18 and 30 days old. At 45 days old, the pepsinogen cells appeared in the bottom of the gland, and consequently the RGL cells were located in the mid-zone of the gastric glands, between mitotic cells (neck of the gland) and pepsinogen cells (lower part of the gland). Ultrastructural study of cardial gastric glands revealed different morphologies of the secretion granules in the cells along the gastric glands. In 6-day-old rabbits, secretory granules were found uniformly electron dense in the bottom of the glands and were RGL-labeled by the immunogold technique. In the medium part of the glands, granules appeared biphasic, with a clear and a dense part, and RGL labeling was confined to the electron-dense part.(ABSTRACT TRUNCATED AT 250 WORDS)     

Morphological and biochemical adaptations to feeding in some herbivorous gastropods

Feeding range and modes as well as morphological and biochemical adaptations to feeding are analyzed in herbivorous mollusks. The content of hemoglobin in radular tissues and weight properties of the radula are evaluated for different modes of feeding.Translated from Izvestiya Akademii Nauk, Seriya Biologicheskaya, No. 1, 2005, pp. 69–77.Original Russian Text Copyright © 2005 by Alyakrinskaya.     

Structural and histochemical changes in the salivary glands of Rhipicephalus appendiculatus during feeding

The salivary glands of the brown ear tick of cattle, R. appendiculatus, from both sexes and at all stages of feeding, were examined as whole glands and as sections for ultrastructural and histochemical changes. The type 1 acinus consists of a basal labyrinth formed by the interdigitations of a central cell and four peripheral cells. These cells form a specialized border with a central constrictor cell which surrounds the acinar duct. The plasma membrane of the central cell is exposed to the duct. The type 1 acini do not appear to secrete active saliva components involved in feeding. The type 2 acini undergo a great increase in synthetic and secretory activity during feeding in both sexes and secrete a lipoprotein probably to form part of the attachment cone and also glycoproteins and esterases of unknown functions. The type 3 acini of both sexes also secrete a lipoprotein probably to form part of the attachment cone. The f cells of these acini in the females transiently secrete a glycoprotein of unknown function and then transform to become part of a water excreting unit. In the males the secretory activity of the granular cells of the type 2 and 3 acini is maintained for further attachments. The type 4 acini of the males accumulate masses of proteinaceous granules. The system of interstitial cells and intercellular spaces in types 2, 3 and 4 acini is large and increasingly active during feeding.     

Intravenous infusion of glucagon-like peptide-1 potently inhibits food intake, sham feeding, and gastric emptying in rats

Glucagon-like peptide-1(7-36)-amide (GLP-1) is postulated to act as a hormonal signal from gut to brain to inhibit food intake and gastric emptying. A mixed-nutrient meal produces a 2 to 3-h increase in plasma GLP-1. We determined the effects of intravenous infusions of GLP-1 on food intake, sham feeding, and gastric emptying in rats to assess whether GLP-1 inhibits food intake, in part, by slowing gastric emptying. A 3-h intravenous infusion of GLP-1 (0.5-170 pmol.kg(-1).min(-1)) at dark onset dose-dependently inhibited food intake in rats that were normally fed with a potency (mean effective dose) and efficacy (maximal % inhibition) of 23 pmol.kg(-1).min(-1) and 82%, respectively. Similar total doses of GLP-1 administered over a 15-min period were less potent and effective. In gastric emptying experiments, GLP-1 (1.7-50 pmol.kg(-1).min(-1)) dose-dependently inhibited gastric emptying of saline and ingested chow with potencies of 18 and 6 pmol.kg(-1).min(-1) and maximal inhibitions of 74 and 83%, respectively. In sham-feeding experiments, GLP-1 (5-50 pmol.kg(-1).min(-1)) dose-dependently reduced 15% aqueous sucrose intake in a similar manner when gastric cannulas were closed (real feeding) and open (sham feeding). These results demonstrate that intravenous infusions of GLP-1 dose-dependently inhibit food intake, sham feeding, and gastric emptying with a similar potency and efficacy. Thus GLP-1 may inhibit food intake in part by reducing gastric emptying, yet can also inhibit food intake independently of its action to reduce gastric emptying. It remains to be determined whether intravenous doses of GLP-1 that reproduce postprandial increases in plasma GLP-1 are sufficient to inhibit food intake and gastric emptying.     

Microwear, mechanics and the feeding adaptations of Australopithecus africanus

Recent studies of dental microwear and craniofacial mechanics have yielded contradictory interpretations regarding the feeding ecology and adaptations of Australopithecus africanus. As part of this debate, the methods used in the mechanical studies have been criticized. In particular, it has been claimed that finite element analysis has been poorly applied to this research question. This paper responds to some of these mechanical criticisms, highlights limitations of dental microwear analysis, and identifies avenues of future research.     

Transepithelial transport and enzymatic detoxification of gluten in gluten-sensitive rhesus macaques

Background and Aims

In a previous report, we characterized a condition of gluten sensitivity in juvenile rhesus macaques that is similar in many respects to the human condition of gluten sensitivity, celiac disease. This animal model of gluten sensitivity may therefore be useful toward studying both the pathogenesis and the treatment of celiac disease. Here, we perform two pilot experiments to demonstrate the potential utility of this model for studying intestinal permeability toward an immunotoxic gluten peptide and pharmacological detoxification of gluten in vivo by an oral enzyme drug candidate.

Methods

Intestinal permeability was investigated in age-matched gluten-sensitive and control macaques by using mass spectrometry to detect and quantify an orally dosed, isotope labeled 33-mer gluten peptide delivered across the intestinal epithelium to the plasma. The protective effect of a therapeutically promising oral protease, EP-B2, was evaluated in a gluten-sensitive macaque by administering a daily gluten challenge with or without EP-B2 supplementation. ELISA-based antibody assays and blinded clinical evaluations of this macaque and of an age-matched control were conducted to assess responses to gluten.

Results

Labeled 33-mer peptide was detected in the plasma of a gluten-sensitive macaque, both in remission and during active disease, but not in the plasma of healthy controls. Administration of EP-B2, but not vehicle, prevented clinical relapse in response to a dietary gluten challenge. Unexpectedly, a marked increase in anti-gliadin (IgG and IgA) and anti-transglutaminase (IgG) antibodies was observed during the EP-B2 treatment phase.

Conclusions

Gluten-sensitive rhesus macaques may be an attractive resource for investigating important aspects of celiac disease, including enhanced intestinal permeability and pharmacology of oral enzyme drug candidates. Orally dosed EP-B2 exerts a protective effect against ingested gluten. Limited data suggest that enhanced permeability of short gluten peptides generated by gastrically active glutenases may trigger an elevated antibody response, but that these antibodies are not necessarily causative of clinical illness.     

Proliferative reaction of the epithelium of gastric glands to vagotomy and sympathectomy

By means of autoradiography and metaphase arrest technique 24-hour rhythms and intensity of proliferative processes in the epithelium of gastric glands were studied, as well as morphometric status of these structures after vagotomy and drug sympathectomy in the rat. In both cases the reaction of glandular epithelium appeared with the increase of mitotic activity and the decrease of cell synchronization before the entry into DNA--synthesis and mitosis. The number of epithelial cells in gastric glands became reduced, but after vagotomy, unlike sympathectomy, mainly because of the lack of chief cells. Thus, the trophic control upon the dynamic structure of gastric glands may have different mechanisms of realization for parasympathetic and sympathetic nervous system, probably, through the influence on cell proliferation or differentiation.     

Maternal protein homeostasis and milk protein synthesis during feeding and fasting in humans

Little is known about amino acid (AA) and protein metabolism in lactating women. We hypothesized: 1) AA sources other than the plasma acid pool provide substrate for milk protein synthesis in humans and 2) if albumin was one such source, then albumin fractional synthesis rate (FSR) is higher in the lactating women. To test these hypotheses, six healthy exclusively breast-feeding women [27 +/- 3 yr; body mass index (BMI) 26 +/- 2 kg/m2] between 6 wk and 3 mo postpartum and six healthy nonlactating women (28 +/- 2 yr; BMI 22 +/- 1 kg/m2) were studied two times, in random order, during 22 h fasting or 10 h of continuous feeding with a mixed nutrient drink. Protein metabolism was determined using [1-13C]leucine and [15N2]urea. In both the fed and fasted states, a significant portion of milk protein (20 +/- 5 and 31 +/- 6%, respectively) was derived from sources other than the plasma free AA pool. A 70% higher (P < 0.02) FSR of albumin was observed in lactating women during feeding, suggesting that albumin is a likely source of AA for milk protein synthesis. We conclude that plasma free AA contribute only 70-80% of the substrate for milk protein synthesis in humans and that albumin may be a significant source of amino acids for the remainder.     

Control of adaptations in protein levels in response to exercise

The nature of the contractile stimuli to which a skeletal muscle is subjected determines which proteins will increase in skeletal muscle. Rates of muscle protein synthesis decrease during an exercise bout for durations of less than 30 min. Synthesis has been reported to increase, remain unchanged, or decrease during exercise bouts lasting from 30 min to 7 h. Protein synthesis rates apparently increase when exercise exceeds 7 h. After short bouts of exercise, protein synthesis rates in muscles appear to decrease in the first hour after exercise, but in the second hour after exercise increase to levels greater than normal. We hypothesize that decreases in ATP and pH levels in muscle during contractile activity may dampen a calcium-mediated stimulation of translation of RNA. That the content of alpha-actin mRNA in muscles of immobilized limbs is unchanged when actin synthesis initially decreases suggests that a decrease in the translation of alpha-actin mRNA is the facilitating step in the decrease in actin synthesis. Rates of muscle protein degradation decrease during exercise if exercise duration is less than 12 h, but increase when exercise is continuous for a day. After intense exercise, rates of protein degradation in skeletal muscle may be increased. An increased ratio of NAD(P)H:NAD(P) in muscle during short-term exercise may decrease degradation. Increased lysosomal enzyme activity in muscle occurs during the postexercise period.     

Morphocytochemical reaction of the main exocrinocytes of the proper gastric glands to orchiectomy

In the experiment performed on 52 white male rats by means of light and electron microscopy, cytochemistry and biochemistry, it has been stated that bilateral removal of the testes inhibits proliferation of epitheliocytes in the collum of the proper gastric glands and their differentiation into the main exocrinocytes. This results in decreasing amount of the latter and in development of certain destructive processes in them. They concern mainly the protein-synthesizing apparatus and to a less degree the mitochondrial and lysosomal apparatus. RNA content, ATPase activity oxidoreductase of Krebs cycle and pentose-phosphate shunt decreases, and that of glycolysis increase. Pepsinogen synthesis and its extrusion are inhibited; this is accompanied with a decreased proteolytic activity of the gastric juice. Regenerative processes in the main exocrinocytes are also inhibited.     

Female tick Hyalomma marginatum marginatum salivary glands: preliminary study on protein changes during feeding process and antigens recognized by repeatedly infested cattle

Proteins extracted from salivary glands of unfed, three days and five days fed adult Hyalomma marginatum marginatum were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). We have noticed changes during the three feeding steps. Some proteins disappeared during feeding process (23, 38, 39, 40 to 50, 95 and 112 kDa), they might be proteins which were converted in other substances and are secreted. Other antigens (13 to 14, 20, 25, 29, 165 and 210 kDa) were synthesized as a result of tick attachment and feeding. They may be related to growth and development or are the ciment which fixed the adult. Also, three Holstein calves were infested five times with 100 pairs of adult ticks of the same species. The five infestations were performed two weeks from the previous infestation. The sera before infestations and after each infestation were used in western-blot analyses to identify antigens from five days salivary gland extracts of the primary infestation of ticks. Three antigens (18.7, 50 and 80 kDa) were revealed weakly after the first and the second infestations by sera samples but not at infestation onward. Others (13.5, 17 to 18.5, 25, 30, 70, 133, 176 and 193 kDa) were revealed only by sera taken after manifestation of resistance (third infestation). A 13.5 kDa antigen was particularly revealed when resistance had appeared and became more evident after the fourth and fifth infestations. The late antigens recognized might be associated with establishment of calves resistance against ticks.