Nutrient Catabolism Research Articles

Introduction to serial reviews: health beneficial effects of food factors can be applicable to humans?

A huge number of reports concerning food factors have been published, claiming beneficial health effects. However, these reports often include several critical questions; whether the beneficial effects can be reproduced in humans, whether the beneficial factors produce side effects, and whether the effects are biologically beneficial or toxic. Many of these reports employed cell lines to examine the effects of food factors. In humans, dietary food factors first pass through the digestive tract and undergo selection to be incorporated into blood in the intestinal epithelium. The data obtained in cell line experiments are not applicable to humans. Food factors are classified into nutrients and non-nutrients.(1) Nutrients are sugars, lipids and proteins, and undergo decomposable catabolism and finally produce ATP energy. Vitamins and minerals, being essential in nutrient catabolism, are also classified as nutrients. The nutrients are recognized by transporters in the epithelium and incorporated into the blood circulation, or are recognized by endogenous carrier proteins after incorporation by simple diffusion into epithelium. In contrast, non-nutrients cannot undergo catabolism and cannot produce ATP. Thus, if absorbed into the body, non-nutrients exist as the same chemical forms in foods because they do not undergo catabolism. Chemicals that cannot undergo catabolism act randomly on biologically important components and exhibit diverse bioactivities, and then disrupt the homeostasis of the metabolism. To avoid disruption, the epithelium inactivates non-nutrients by conjugations such as glucuronization and sulfation before incorporating them into the blood, or excretes them onto the lumen side.(2–5) A small amount of incorporated non-nutrients is excreted into urine after short circulation in the blood. Non-nutrients in food include around 8,000 species of phenolics, including phenylpropanoids, flavonoids and anthraquinones; about 25,000 terpenoids, including terpenes, carotenoids, xanthophylls, and iridoids; 12,000 alkaloids, and several sulfate-containing chemicals such as isothiocyanates and sulforaphane. Among these non-nutrients, bioavailable substances for the health beneficial effects are limited when ingested by humans. Animal experiments provide evidence for the health beneficial effects of various food factors. Animals can select non-nutrients for incorporation into the epithelium; however, most experimental animals are nocturnal and differ in circadian rhythm form humans. The questions remains whether the data obtained in animal experiments can be applied to humans. In this serial review, bioavailable and effective food factors in humans, factors converted into be highly bioavailable and effective forms in the intestinal flora of the human digestive tract, factors that can exhibit modulating activity on the immune response by affecting the intestinal epithelium, the validity of the results of animal experiments for humans, and a new theory that the health beneficial effects of non-nutrients modulate the quality control system of endogenous proteins, will be discussed.

Increased Anaplerosis, TCA Cycling, and Oxidative Phosphorylation in the Liver of Dairy Cows with Intensive Body Fat Mobilization during Early Lactation

The onset of milk production lets mammals experience an enormous energy and nutrient demand. To meet these requirements, high-yielding dairy cows mobilize body fat resulting in an augmented hepatic oxidative metabolism, which has been suggested to signal for depressing hunger after calving. To examine how the extent of fat mobilization influences hepatic oxidative metabolism and thus potentially feed intake, blood and liver samples of 19 Holstein cows were taken throughout the periparturient period. Retrospectively grouped according to high (H) and low (L) liver fat content, H cows showed higher fatty acid but lower amino acid plasma concentrations and lower feed intake than L cows. The hepatic phospho-AMPK/total AMP ratio was not different between groups but decreased after parturition. A 2-DE coupled MALDI-TOF-TOF analysis and qRT-PCR studies revealed H cows having lower expressions of major enzymes involved in mitochondrial β-oxidation, urea cycling, and the pentose phosphate pathway but higher expressions of enzymes participating in peroxisomal and endoplasmic fatty acid degradation, pyruvate and TCA cycling, amino acid catabolism, oxidative phosphorylation, and oxidative stress defense. These data indicate that increasing lipolysis leads to augmenting nutrient catabolism for anaplerosis and mitochondrial respiration, providing a molecular link between hepatic oxidative processes and feed intake.

Intracellular growth and pathogenesis of Leishmania parasites

Parasitic protozoa belonging to the genus Leishmania are the cause of a spectrum of diseases in humans, as well as chronic long-term infections. These parasites exhibit a remarkable capacity to survive and proliferate within the phagolysosome compartment of host macrophages. Studies with defined Leishmania mutants in mouse models of infection have highlighted processes that are required for parasite survival in macrophages. Parasite mutants have been identified that (i) are poorly virulent when the insect (promastigote) stage is used to initiate infection, but retain wild-type virulence following transformation to the obligate intracellular amastigote stage, (ii) are highly attenuated when either promastigotes or amastigotes are used, and (iii) are unable to induce characteristic lesion granulomas, but can persist within macrophages in other tissues. From these analyses it can be concluded that promastigote stages of some species require the surface expression of lipophosphoglycan, but not other surface components. Survival and subsequent proliferation of Leishmania in macrophages requires the activation of heat-shock responses (involving the up-regulation and/or phosphorylation of heat-shock proteins), the presence of oxidative and nitrosative defence mechanisms, and uptake and catabolism of carbon sources (glycoproteins, hexoses and amino acids) and essential nutrients (purines, amino acids and vitamins). Parasite mutants with defects in specific kinase/phosphatase-dependent signalling pathways are also severely attenuated in amastigote virulence, highlighting the potential importance of post-translational regulatory mechanisms in parasite adaptation to this host niche.

Digestible nutrients and available (ATP) energy contents of two varieties of kiwifruit (Actinidia deliciosa and Actinidia chinensis)

A model, which combines a dual in vivo–in vitro digestibility assay and stoichiometric relationships describing nutrient catabolism, has been recently developed to allow prediction of the available energy (AE) content of a food in terms of its ATP yield. The model uses the growing pig as an in vivo model for upper gastrointestinal tract digestion in humans. Terminal ileal digesta from the pig are incubated with human faecal inocula (in vitro fermentation model) to simulate human hindgut fermentation. The respective in vivo and in vitro digestibility assays provide predictions of the ileal absorbed and hindgut-fermented nutrient contents of a food which are then used to predict ATP production post-absorption, based on known stoichiometric relationships. In this study, the model was used to determine the AE contents of fresh, ripe Hayward (Actinidia deliciosavar Hayward) and Hort16A (Actinidia chinensis var Hort16A) kiwifruit. Kiwifruit pulp, containing 3gkg−1 of titanium dioxide, included as an indigestible marker, was fed to growing pigs and terminal ileal digesta were collected. Ileal nutrient digestibilities were determined. A sample of digesta was incubated in vitro with a fresh human faecal inoculum and the fermentable organic matter determined. The predicted available (ATP) energy contents of the Hayward and Hort16A kiwifruits were 5.9 and 6.2kJg−1 dry matter, respectively, approximately 44–47% of the determined apparent digestible energy (ADE) content. The AE contents of the kiwifruit, expressed relative to the AE content of dextrin (a highly digestible source of glucose) were 0.57 and 0.61 for Hayward and Hort16A, respectively. Comparable ratios for metabolisable energy (ME) were 0.74 and 0.73. The predicted AE from kiwifruit was much lower than the predicted ME from kiwifruit when compared to dextrin. The ME values overestimate the energy content of kiwifruit that is available to the cell. AE was not only lower than ME but the two energy systems ranked the kiwifruit types differently in terms of energy supply to the body. The relatively low energy content per unit of dry matter and high water content of kiwifruit make kiwifruit an ideal weight loss food.

IL-4/STAT6 immune axis regulates peripheral nutrient metabolism and insulin sensitivity

Immune cells take residence in metabolic tissues, providing a framework for direct regulation of nutrient metabolism. Despite conservation of this anatomic relationship through evolution, the signals and mechanisms by which the immune system regulates nutrient homeostasis and insulin action remain poorly understood. Here, we demonstrate that the IL-4/STAT6 immune axis, a key pathway in helminth immunity and allergies, controls peripheral nutrient metabolism and insulin sensitivity. Disruption of signal transducer and activator of transcription 6 (STAT6) decreases insulin action and enhances a peroxisome proliferator-activated receptor α (PPARα) driven program of oxidative metabolism. Conversely, activation of STAT6 by IL-4 improves insulin action by inhibiting the PPARα-regulated program of nutrient catabolism and attenuating adipose tissue inflammation. These findings have thus identified an unexpected molecular link between the immune system and macronutrient metabolism, suggesting perhaps the coevolution of these pathways occurred to ensure access to glucose during times of helminth infection.

Expression of the Electrogenic Na+-HCO3--Cotransporter NBCe1 in Tumoral Insulin-Producing BRIN-BD11 Cells

Background/aims: The expression of the electrogenic Na⁺-HCO₃^--cotransporter NBCe1 was recently documented in rat pancreatic islet B-cells, it being speculated that such a protein participates in the extrusion of bicarbonate generated by the oxidative catabolism of nutrients from insulin-producing cells. Considering the prevalence of a Crabtree effect in tumoral insulin-producing cells, the possible presence of NBCe1 was now investigated in BRIN-BD11 cells, an insulin-producing cell line established by electrofusion of normal pancreatic B-cells with immortalized RINm5F cells. Methods: The possible presence of NBCe1 in BRIN-BD11 cells was investigated by RT-PCR, western blot analysis and immunocytochemistry. The release of insulin and net uptake of ²²Na⁺ were also measured in the BRIN-BD11 cells. Results: RT-PCR, western blot analysis and immunocytochemistry documented the presence of NBCe1 in BRIN-BD11 cells. A reported inhibitor of NBCe1, i.e. tenidap, (50-100 μM), inhibited basal and hypotonicity-induced insulin release from the BRIN-BD11 cells, whilst increasing the net uptake of ²²Na⁺ by the same cells. The latter effect was, in relative terms, more pronounced in the presence than absence of ouabain. Conclusion: BRIN-BD11 cells, like normal pancreatic islet B-cells, express NBCe1, with predominance of the B variant of this electrogenic Na⁺-HCO₃^--cotransporter.

Differential Gene Expression in Human Conducting Airway Surface Epithelia and Submucosal Glands

Human conducting airways contain two anatomically distinct epithelial cell compartments: surface epithelium and submucosal glands (SMG). Surface epithelial cells interface directly with the environment and function in pathogen detection, fluid and electrolyte transport, and mucus elevation. SMG secrete antimicrobial molecules and most of the airway surface fluid. Despite the unique functional roles of surface epithelia and SMG, little is known about the differences in gene expression and cellular metabolism that orchestrate the specialized functions of these epithelial compartments. To approach this problem, we performed large-scale transcript profiling using epithelial cell samples obtained by laser capture microdissection (LCM) of human bronchus specimens. We found that SMG expressed high levels of many transcripts encoding known or putative innate immune factors, including lactoferrin, zinc alpha-2 glycoprotein, and proline-rich protein 4. By contrast, surface epithelial cells expressed high levels of genes involved in basic nutrient catabolism, xenobiotic clearance, and ciliated structure assembly. Selected confirmation of differentially expressed genes in surface and SMG epithelia demonstrated the predictive power of this approach in identifying genes with localized tissue expression. To characterize metabolic differences between surface epithelial cells and SMG, immunostaining for a mitochondrial marker (isocitrate dehydrogenase) was performed. Because greater staining was observed in the surface compartment, we predict that these cells use significantly more energy than SMG cells. This study illustrates the power of LCM in defining the roles of specific anatomic features in airway biology and may be useful in examining how disease states alter transcriptional programs in the conducting airways.

Genetic variation in sialidase and linkage to N-acetylneuraminate catabolism in Mycoplasma synoviae

We explored the genetic basis for intraspecific variation in mycoplasmal sialidase activity that correlates with virulence, and its potentially advantageous linkage to nutrient catabolism. Polymorphism in N-acetylneuraminate scavenging and degradation genes (sialidase, N-acetylneuraminate lyase, N-acetylmannosamine kinase, N-acetylmannosamine-6-phosphate epimerase, N-acetylglucosamine-6-phosphate deacetylase, and glucosamine-6-phosphate deaminase) was evident among eight strains of the avian pathogen Mycoplasma synoviae. Most differences were single nucleotide polymorphisms, ranging from 0.34 ± 0.04 substitutions per 100 bp for N-acetylmannosamine kinase to 0.65 ± 0.03 for the single-copy sialidase gene nanI. Missense mutations were twice as common as silent mutations in nanI; 26% resulted in amino acids dissimilar to consensus; and there was a 12-base deletion near the nanI promoter in strain WVU1853 T, supporting a complex genetic basis for differences in sialidase activity. Two strains had identical frameshifts in the N-acetylneuraminate lyase gene nanA, resulting in nonsense mutations, and both had downstream deletions in nanA. Such genetic lesions uncouple extracellular liberation of sialic acid from generation of fructose-6-phosphate and pyruvate via intracellular N-acetylneuraminate degradation. Retention of nanI by such strains, but not others in the M. synoviae phylogenetic cluster, is evidence that sialidase has an important non-nutritional role in the ecology of M. synoviae and certain other mycoplasmas.

Lessons from “Lower” Organisms: What Worms, Flies, and Zebrafish Can Teach Us about Human Energy Metabolism

A pandemic of metabolic diseases (atherosclerosis, diabetes mellitus, and obesity), unleashed by multiple social and economic factors beyond the control of most individuals, threatens to diminish human life span for the first time in the modern era. Given the redundancy and inherent complexity of processes regulating the uptake, transport, catabolism, and synthesis of nutrients, magic bullets to target these diseases will be hard to find. Recent studies using the worm Caenorhabditis elegans, the fly Drosophila melanogaster, and the zebrafish Danio rerio indicate that these “lower” metazoans possess unique attributes that should help in identifying, investigating, and even validating new pharmaceutical targets for these diseases. We summarize findings in these organisms that shed light on highly conserved pathways of energy homeostasis.

Responses to nutrients in farm animals: implications for production and quality

It is well known that any quantitative (energy and protein levels) and qualitative (nature of the diet, nutrient dynamic) changes in the feeding of animals affect metabolism. Energy expenditure and feed efficiency at the whole-body level, nutrient partitioning between and within tissues and organs and, ultimately, tissue and organ characteristics are the major regulated traits with consequences on the quality of the meat and milk produced. Recent progress in biology has brought to light important biological mechanisms which explain these observations: for instance, regulation by the nutrients of gene expression or of key metabolic enzyme activity, interaction and sometimes cross-regulation or competition between nutrients to provide free energy (ATP) to living cells, indirect action of nutrients through a complex hormonal action, and, particularly in herbivores, interactions between trans-fatty acids produced in the rumen and tissue metabolism. One of the main targets of this nutritional regulation is a modification of tissue insulin sensitivity and hence of insulin action. In addition, the nutritional control of mitochondrial activity (and hence of nutrient catabolism) is another major mechanism by which nutrients may affect body composition and tissue characteristics. These regulations are of great importance in the most metabolically active tissues (the digestive tract and the liver) and may have undesirable (i.e. diabetes and obesity in humans) or desirable consequences (such as the production of fatty liver by ducks and geese, and the production of fatty and hence tasty meat or milk with an adapted fatty acid profile).

Small Bowel Bacterial Overgrowth: Presentation, Diagnosis, and Treatment.

Small bowel bacterial overgrowth (SBBO) syndrome is associated with excessive numbers of bacteria in the proximal small intestine. The pathology of this condition involves competition between the bacteria and the human host for ingested nutrients. This competition leads to intraluminal bacterial catabolism of nutrients, often with production of toxic metabolites and injury to the enterocyte. A complex array of clinical symptoms ensues, resulting in chronic diarrhea, steatorrhea, macrocytic anemia, weight loss, and less commonly, protein-losing enteropathy. Therapy is targeted at correction of underlying small bowel abnormalities that predispose to SBBO and appropriate antibiotic therapy. The symptoms and signs of SBBO can be reversed with this approach.

Small bowel bacterial overgrowth: presentation, diagnosis, and treatment.

Small bowel bacterial overgrowth (SBBO) syndrome is associated with excessive numbers of bacteria in the proximal small intestine. The pathology of this condition involves competition between the bacteria and the human host for ingested nutrients. This competition leads to intraluminal bacterial catabolism of nutrients, often with production of toxic metabolites and injury to the enterocyte. A complex array of clinical symptoms ensues, resulting in chronic diarrhea, steatorrhea, macrocytic anemia, weight loss, and less commonly, protein-losing enteropathy. Therapy is targeted at correction of underlying small bowel abnormalities that predispose to SBBO and appropriate antibiotic therapy. The symptoms and signs of SBBO can be reversed with this approach.

Effects of starvation, season, and diet on the free amino acid and protein content of Calanus finmarchicus females

Effects of food availability and season on the free amino acid (FAA) and total protein content of the copepod Calanus finmarchicus females were investigated in two mesocosm experiments on the Norwegian west coast in spring and autumn. Starved C. finmarchicus females showed no change in total FAA content, but the FAA pool composition changed drastically. During the first 10 days of starvation the protein content showed a moderate decline (<2 μg ind−1); however, during the following 21 days the total content was drastically reduced, from 63 to 9 μg ind−1. This supports the notion of a sequential catabolism of endogenous nutrients during starvation. In females at high food concentrations, the body protein content increased during spring, but decreased during autumn. The FAA pool composition of females differed between spring and autumn in 14 of the 18 FAA investigated. Reduced body protein content and increased proportion of essential free amino acid were observed during starvation. Similar changes were observed in females sampled at the end of the mesocosm experiments in the autumn. The results suggest that mature C. finmarchicus females are in a negative protein balance during autumn, despite high food concentrations, contributing to a lower fitness than in females maturing during the spring.

The Immunosuppressant Rapamycin Mimics a Starvation-Like Signal Distinct from Amino Acid and Glucose Deprivation

RAFT1/FRAP/mTOR is a key regulator of cell growth and division and the mammalian target of rapamycin, an immunosuppressive and anticancer drug. Rapamycin deprivation and nutrient deprivation have similar effects on the activity of S6 kinase 1 (S6K1) and 4E-BP1, two downstream effectors of RAFT1, but the relationship between nutrient- and rapamycin-sensitive pathways is unknown. Using transcriptional profiling, we show that, in human BJAB B-lymphoma cells and murine CTLL-2 T lymphocytes, rapamycin treatment affects the expression of many genes involved in nutrient and protein metabolism. The rapamycin-induced transcriptional profile is distinct from those induced by glucose, glutamine, or leucine deprivation but is most similar to that induced by amino acid deprivation. In particular, rapamycin treatment and amino acid deprivation up-regulate genes involved in nutrient catabolism and energy production and down-regulate genes participating in lipid and nucleotide synthesis and in protein synthesis, turnover, and folding. Surprisingly, however, rapamycin had effects opposite from those of amino acid starvation on the expression of a large group of genes involved in the synthesis, transport, and use of amino acids. Supported by measurements of nutrient use, the data suggest that RAFT1 is an energy and nutrient sensor and that rapamycin mimics a signal generated by the starvation of amino acids but that the signal is unlikely to be the absence of amino acids themselves. These observations underscore the importance of metabolism in controlling lymphocyte proliferation and offer a novel explanation for immunosuppression by rapamycin.

Dietary effects on insulin and nutrient metabolism in mesenteric lymph node cells, splenocytes, and pancreatic islets of BB rats

The present studies were performed to determine if a protective diet has different effects on the metabolic activity or function of islet cells, as well as the metabolic activity of mesenteric lymph node (MLN) cells and spleen cells, from BioBreeding (BB) rats. Diabetes-prone BB (BBdp) rats and control non–diabetes-prone BB (BBc) rats were fed for about 20 days either a mainly plant-based diabetogenic diet, NIH-07 (NIH), or a protective semipurified diet with hydrolyzed casein (HC) as the amino acid source. At 6 to 8 weeks of age, BBdp rats had high plasma D-glucose and low insulin concentrations, low insulin content, and low metabolic and secretory responses to D-glucose in isolated pancreatic islets. Islet metabolism, as measured by accumulation of 14C-acidic metabolites, amino acids, and the ratio of D-[U-14C]glucose oxidation and D-[5-3H]glucose utilization was increased in control rats fed HC (P < .05); a similar trend in BBdp rats was not significant. Feeding the HC diet increased islet insulin content (P < .01) by 13% in BBdp and 23% in BBc rats; other metabolic and hormonal variables were unaffected. Compared with BBc rats, BBdp rats displayed higher rates of L-[U-14C]glutamine oxidation, D-[5-3H]glucose utilization, and D-[U-14C]glucose oxidation in MLN cells, but not in splenocytes. There was a dramatic decrease of L-[U-14C]glutamine oxidation in MLN cells from BBc and BBdp rats fed HC. Glycolysis was decreased in control rats. We conclude that the protection afforded by feeding BBdp rats a HC diet is associated with increased insulin in target β cells and downregulation of metabolic activity in gut-associated MLN cells. Metabolic activity in splenocytes, cells representative of the systemic immune system, was less affected. These data suggest that diet-induced metabolic changes occur in the islets and nearby cells of the gut immune system in the period before classic insulitis. Changes in the islets were smaller in comparison to the dramatic remodeling of nutrient catabolism in MLN cells. MLN downregulation may reflect baseline metabolic activity in the absence of diabetogenic (or other) food antigens and further highlights an important interaction between diabetogenic food antigens and the gut immune tissues.

Feeding a protective hydrolysed casein diet to young diabetic-prone BB rats affects oxidation of L[U-14C]glutamine in islets and Peyer's patches, reduces abnormally high mitotic activity in mesenteric lymph nodes, enhances islet insulin and tends to normalize NO production.

The present studies were undertaken to examine concomitant diet-induced changes in pancreatic islets and cells of the gut immune system of diabetes-prone BB rats in the period before classic insulitis. Diabetes-prone (BBdp) and control non-diabetes prone (BBc) BB rats were fed for ~ 17 days either a mainly plant-based standard laboratory rodent diet associated with high diabetes frequency, NIH-07 (NIH) or a protective semipurified diet with hydrolyzed casein (HC) as the amino acid source. By about 7 weeks of age, NIH-fed BBdp rats had lower plasma insulin and insulin/glucose ratio, lower insulin content of isolated islets, lower basal levels of NO but higher responsiveness of NO production to IL-1β in cultured islets, and higher Con A response and biosynthetic activities in mesenteric lymphocytes than control rats fed the same diet. In control rats, the HC diet caused only minor changes in most variables, except for a decrease in oxidation of L-[U−C14]glutamine in Peyer's patch (PP) cells and an increase in protein biosynthesis in mesenteric lymphocytes. In BBdp rats, however, the HC diet increased plasma insulin concentration, islet insulin/ protein ratio, and tended to normalize the basal and IL-1β-stimulated NO production by cultured islets. The HC diet decreased oxidation of L-[U−C14]glutamine in BBdp pancreatic islets, whereas oxidation of L-[U−C14]glutamine in PP cells was increased, and the basal [Methyl-H3] thymidine incorporation in mesenteric lymphocytes was decreased. These findings are compatible with the view that alteration of nutrient catabolism in islet cells as well as key cells of the gut immune system, particularly changes in mitotic and biosynthetic activities in mesenteric lymphocytes, as well as basal and IL-1β stimulated NO production, participate in the sequence of events leading to autoimmune diabetes in BB rats. Thus, the protection afforded by feeding a hydrolysed casein-based diet derives from alterations in both the target islet tissue and key cells of the gut immune system in this animal model of type 1 diabetes.

Metabolic and secretory interactions between D-glucose and D-fructose in islets from GK rats.

The metabolism of D-glucose and/or D-fructose was investigated in both pancreatic islets and parotid cells of control and hereditarily diabetic Goto-Kakizaki (GK) rats. In the islets from GK rats, a preferential alteration of the oxidative response to D-glucose coincided with an impaired secretory response to the aldohexose. Such a metabolic alteration was not found in the parotid cells of GK rats. Whether in islet or parotid cells, D-fructose little affected the catabolism of glucose in either control or GK rats. The metabolism of D-fructose and the effect of D-glucose thereupon were essentially comparable in control and GK rats in both pancreatic islets and parotid cells. In both cell types, the comparison between the metabolism of D-glucose and D-fructose in cells simultaneously exposed to the two hexoses suggested a far from negligible contribution of fructokinase to the phosphorylation of D-fructose. Although the catabolism of the ketohexose and its modulation by D-glucose were closely comparable in islets from control and GK rats, the insulinotropic action of the ketohexose, relative to that of the aldohexose, was severely impaired in the GK rats. The present work thus emphasizes the specificity of the alteration in D-glucose metabolism in islets, as opposed to extrapancreatic cells, of GK rats. It also reveals in the islets of GK rats a further secretory anomaly apparently not attributable to the impairment of nutrient catabolism in the islet cells of these diabetic animals.

Metabolic and Secretory Interactions between D-Glucose and D-Fructose in Islets from GK Rats

The metabolism of d-glucose and/or d-fructose was investigated in both pancreatic islets and parotid cells of control and hereditarily diabetic Goto-Kakizaki (GK) rats. In the islets from GK rats, a preferential alteration of the oxidative response to d-glucose coincided with an impaired secretory response to the aldohexose. Such a metabolic alteration was not found in the parotid cells of GK rats. Whether in islet or parotid cells, d-fructose little affected the catabolism of glucose in either control or GK rats. The metabolism of d-fructose and the effect of d-glucose thereupon were essentially comparable in control and GK rats in both pancreatic islets and parotid cells. In both cell types, the comparison between the metabolism of d-glucose and d-fructose in cells simultaneously exposed to the two hexoses suggested a far from negligible contribution of fructokinase to the phosphorylation of d-fructose. Although the catabolism of the ketohexose and its modulation by d-glucose were closely comparable in islets from control and GK rats, the insulinotropic action of the ketohexose, relative to that of the aldohexose, was severely impaired in the GK rats. The present work thus emphasizes the specificity of the alteration in d-glucose metabolism in islets, as opposed to extrapancreatic cells, of GK rats. It also reveals in the islets of GK rats a further secretory anomaly apparently not attributable to the impairment of nutrient catabolism in the islet cells of these diabetic animals.

The changing nature of small intestine bacterial overgrowth.

Small intestine bacterial overgrowth is also known as the blind loop, stagnant loop, or stasis syndrome, the syndrome associated with the excessive numbers of bacteria in the proximal small intestine. The pathophysiology of this condition involves competition between the bacteria and the human host for ingested nutrients. This leads to intraluminal bacterial catabolism of nutrients, often with production of and inury to the enterocyte. A complex array of clinical symptoms ensues, resulting in intestinal malabsorption, weight loss, and malnutrition. These symptoms and signs can be reversed with appropriate antimicrobial therapy.

Effect of N-[( trans-4-Isopropylcyclohexyl)- carbonyl]- d-phenylalanine on Nutrient Catabolism in Rat Pancreatic Islets

1. The effect of N-[( trans-4-isopropylcyclohexyl)-carbonyl]- D-phenylalanine (A-4166) on nutrient metabolism was investigated in isolated rat pancreatic islets. 2. At a 10-μM concentration, the meglitinide analogue caused a modest increase in 14CO 2 output from islets prelabeled with L-[U- 14C]glutamine but failed to affect D-[5- 3H]glucose utilization, D-[U- 14C]glucose oxidation and conversion into 14C-labeled acidic metabolites and amino acids, L[1- 14C]leucine and L-[U- 14C]leucine oxidation, the generation of 2-ketoisocaproate and further acidic metabolites from the branched-chain amino acid and the production of 14CO 2 by islets prelabeled with [U- 14C]palmitate. 3. These findings indicate that the insulinotropic action of A-4166 is not attributable to any sizeable increase in the metabolism of exogenous or endogenous nutrients.