Formation of glucose from hexoses, pentoses, polyols and related substances in kidney cortex.
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ABSTRACT:
SUBMITTER: Krebs HA
PROVIDER: S-EPMC1264817 | biostudies-other | 1966 Jan
REPOSITORIES: biostudies-other
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Project description:1. The aerobic transport of d-glucose and d-galactose in rabbit kidney tissue at 25 degrees was studied. 2. In slices forming glucose from added substrates an accumulation of glucose against its concentration gradient was found. The apparent ratio of intracellular ([S](i)) and extracellular ([S](o)) glucose concentrations was increased by 0.4mm-phlorrhizin and 0.3mm-ouabain. 3. Slices and isolated renal tubules actively accumulated glucose from the saline; the apparent [S](i)/[S](o) fell below 1.0 only at [S](o) higher than 0.5mm. 4. The rate of glucose oxidation by slices was characterized by the following parameters: K(m) 1.16mm; V(max.) 4.5mumoles/g. wet wt./hr. 5. The active accumulation of glucose from the saline was decreased by 0.1mm-2,4-dinitrophenol, 0.4mm-phlorrhizin and by the absence of external Na(+). 6. The kinetic parameters of galactose entry into the cells were: K(m) 1.5mm; V(max) 10mumoles/g. wet wt./hr. 7. The efflux kinetics from slices indicated two intracellular compartments for d-galactose. The galactose efflux was greatly diminished at 0 degrees , was inhibited by 0.4mm-phlorrhizin, but was insensitive to ouabain. 8. The following mechanism of glucose and galactose transport in renal tubular cells is suggested: (a) at the tubular membrane, these sugars are actively transported into the cells by a metabolically- and Na(+)-dependent phlorrhizin-sensitive mechanism; (b) at the basal cell membrane, these sugars are transported in accordance with their concentration gradient by a phlorrhizin-sensitive Na(+)-independent facilitated diffusion. The steady-state intracellular sugar concentration is determined by the kinetic parameters of active entry, passive outflow and intracellular utilization.
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Project description:This work illustrates the feasibility of a microneedle based electrochemical biosensor for continuous glucose monitoring. The device consists of three silk/d-sorbitol pyramidal microneedles integrated with platinum (Pt) and silver (Ag) wires and immobilized glucose selective enzyme (glucose oxidase, GOD) during fabrication. The silk/d-sorbitol composite can provide a biocompatible environment for the enzyme molecules. The break strength can be controlled by the ratio of silk to d-sorbitol, which guarantees microneedle penetrate into skin. The enzymatic-amperometric responses and glucose concentration were linearly correlated, and cover physiological conditions. The microneedle displays high stability both in long-term monitoring and storage, even at 37 °C. Our results reveal that this new microneedle biosensor is a promising tool for wearable minimally invasive continuous glucose monitoring in practical applications.
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Project description:1. When slices of kidney cortex are incubated with lactate and acetoacetate, lactate is almost quantitatively converted into glucose whereas acetoacetate provides a major part of the fuel of respiration. 2. In apparent contrast with these findings a large fraction of (14)C-labelled acetoacetate appears in glucose and a large fraction of (14)C-labelled lactate appears in the carbon dioxide. 3. The findings can be explained by: (a) the participation of oxaloacetate as an intermediate of both gluconeogenesis and respiration; (b) the fact that the carbon dioxide formed in the course of one turn of the tricarboxylic acid cycle is exclusively derived from oxaloacetate. 4. As a result there is a ;crossing over' of the carbon of the substrate of respiration to the pathway of gluconeogenesis and of the carbon of the glucogenic precursors to the pathway of respiration. 5. In the given situation the fate of the label does not allow predictions to be made about the net fate of the labelled metabolites. 6. The implications of the findings on the interpretation of isotopic data are discussed.
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Project description:1. Phosphofructokinase from rat kidney cortex has been partially purified by using a combination of isoelectric and ammonium sulphate precipitation. This preparation was free of enzymes which interfered with the measurement of either product of phosphofructokinase. 2. At concentrations greater than the optimum, ATP caused inhibition which was decreased by raising the fructose 6-phosphate concentration. This suggested that ATP reduced the affinity of phosphofructokinase for the other substrate. Citrate potentiated the ATP inhibition. 3. AMP and fructose 1,6-diphosphate relieved the inhibition by ATP or citrate by increasing the affinity of the enzyme for fructose 6-phosphate. 4. K(+) is shown to stimulate and Ca(2+) to inhibit phosphofructokinase. 5. The similarity between the complex properties of phosphofructokinase from kidney cortex and other tissues (e.g. cardiac and skeletal muscle, brain and liver) suggests that the enzyme in kidney cortex tissue is normally subject to metabolic control, similar to that in other tissues.
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Project description:BackgroundExposure to per- and polyfluoroalkyl substances (PFAS), a prevalent class of persistent pollutants, may increase the risk of type 2 diabetes.ObjectiveWe examined associations between PFAS exposure and glucose metabolism in youth.MethodsOverweight/obese adolescents from the Study of Latino Adolescents at Risk of Type 2 Diabetes (SOLAR; n=310) participated in annual visits for an average of 3.3±2.9y. Generalizability of findings were tested in young adults from the Southern California Children's Health Study (CHS; n=135) who participated in a clinical visit with a similar protocol. At each visit, oral glucose tolerance tests were performed to estimate glucose metabolism and β-cell function via the insulinogenic index. Four PFAS were measured at baseline using liquid chromatography-high-resolution mass spectrometry; high levels were defined as concentrations >66th percentile.ResultsIn females from the SOLAR, high perfluorohexane sulfonate (PFHxS) levels (≥2.0 ng/mL) were associated with the development of dysregulated glucose metabolism beginning in late puberty. The magnitude of these associations increased postpuberty and persisted through 18 years of age. For example, postpuberty, females with high PFHxS levels had 25-mg/dL higher 60-min glucose (95% CI: 12, 39mg/dL; p<0.0001), 15-mg/dL higher 2-h glucose (95% CI: 1, 28mg/dL; p=0.04), and 25% lower β-cell function (p=0.02) compared with females with low levels. Results were largely consistent in the CHS, where females with elevated PFHxS levels had 26-mg/dL higher 60-min glucose (95% CI: 6.0, 46mg/dL; p=0.01) and 19-mg/dL higher 2-h glucose, which did not meet statistical significance (95% CI: -1, 39mg/dL; p=0.08). In males, no consistent associations between PFHxS and glucose metabolism were observed. No consistent associations were observed for other PFAS and glucose metabolism.DiscussionYouth exposure to PFHxS was associated with dysregulated glucose metabolism in females, which may be due to changes in β-cell function. These associations appeared during puberty and were most pronounced postpuberty. https://doi.org/10.1289/EHP9200.
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Project description:The suppression by 3-mercaptopicolinate of gluconeogenesis from glutamine or 2-oxoglutarate in rat or dog kidney tubules did not affect the amount of these substrates undergoing complete oxidation. Furthermore, 3-mercaptopicolinate caused an accumulation of lactate in dog tubules. 3-Mercaptopicolinate abolished both gluconeogenesis and substrate oxidation in tubules from rabbit and guinea-pig kidney. These results imply the presence of an alternative pathway to phosphoenolpyruvate carboxykinase/pyruvate kinase for the production of pyruvate from citric-acid-cycle intermediates in the kidney cortex of rats and dogs but not in that of rabbits or guinea pigs. Oxaloacetate decarboxylase (present in the kidney cortex of all four species) or 'malic' enzyme (present in rat and dog but absent in rabbit and guinea-pig kidney cortex) could function in this role. Our observations indicate that 'malic' enzyme is probably implicated in this phenomenon. The lactate production observed in dog tubules in the presence of 3-mercaptopicolinate can be suppressed when aspartate formation is inhibited by 2-amino-4-methoxy-trans-but-3-enoic acid. This suggests that the provision of cytosolic NADH from citric-acid-cycle intermediates is facilitated by accumulation of aspartate acting as a 'sink' for cytosolic oxaloacetate.
| S-EPMC1161956 | biostudies-other
Project description:Chickpea-based foods are known for their low allergenicity and rich nutritional package. As an essential dietary legume, chickpea is often processed into milk or hummus or as an industrial source of protein and starch. The current study explores the feasibility of using the chickpea-derived prebiotic substances as a scaffold for growing Bacillus subtilis (a prospective probiotic bacterium) to develop synbiotic chickpea-based functional food. We report that the chickpea-derived fibers enhance the formation of the B. subtilis biofilms and the production of the antimicrobial pigment pulcherrimin. Furthermore, electron micrograph imaging confirms the bacterial embedding onto the chickpea fibers, which may provide a survival tactic to shield and protect the bacterial population from environmental insults. Overall, it is believed that chickpea-derived prebiotic substances provide a staple basis for developing functional probiotics and synbiotic food.
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Project description:An extrastriate visual area such as V2 or V4 contains neurons selective for a multitude of complex shapes, all sharing a common topographic organization. Simultaneously developing multiple interdigitated maps--hereafter a "multimap"--is challenging in that neurons must compete to generate a diversity of response types locally, while cooperating with their dispersed same-type neighbors to achieve uniform visual field coverage for their response type at all orientations, scales, etc. Previously proposed map development schemes have relied on smooth spatial interaction functions to establish both topography and columnar organization, but by locally homogenizing cells' response properties, local smoothing mechanisms effectively rule out multimap formation. We found in computer simulations that the key requirements for multimap development are that neurons are enabled for plasticity only within highly active regions of cortex designated "learning eligibility regions" (LERs), but within an LER, each cell's learning rate is determined only by its activity level with no dependence on location. We show that a hybrid developmental rule that combines spatial and activity-dependent learning criteria in this way successfully produces multimaps when the input stream contains multiple distinct feature types, or in the degenerate case of a single feature type, produces a V1-like map with "salt-and-pepper" structure. Our results support the hypothesis that cortical maps containing a fine mixture of different response types, whether in monkey extrastriate cortex, mouse V1 or elsewhere in the cortex, rather than signaling a breakdown of map formation mechanisms at the fine scale, are a product of a generic cortical developmental scheme designed to map cells with a diversity of response properties across a shared topographic space.
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Project description:BACKGROUND:Evidence on the association between exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) and blood glucose concentrations in pregnant women is inconsistent. This study aimed to examine the association between PFAS exposure and the concentrations of fasting plasma glucose (FPG) and one-hour plasma glucose (1 h-PG) after a 50-g oral glucose tolerance test in pregnant women. METHODS:The study was based on the Shanghai-Minhang Birth Cohort, in which 1292 pregnant women were recruited. Among them, 981 women provided blood samples (at 12-16 gestational weeks) for PFAS measurement. FPG data collected from 856 women at 12-20 GW and 1 h-PG data collected from 705 women at 20-28 GW were obtained through medical records from the routine prenatal care system. High FPG or 1 h-PG was defined as ≥90th percentile of FPG or 1 h-PG. The analysis of eight PFASs was conducted in this study: perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUdA), perfluorododecanoic acid (PFDoA), and perfluorotridecanoic acid (PFTrDA). The odds ratios (ORs) and associated 95% confidence intervals (CIs) were estimated to determine the associations of each PFAS compound with high FPG and 1 h-PG from a logistic regression model. RESULTS:After adjustment for potential confounders, most PFASs were positively associated with high 1 h-PG concentrations. The OR for high 1 h-PG concentrations was 1.87 (95% CI: 1.15-3.05) with a one log unit increase of PFOS; similar associations were observed for PFNA (OR: 2.15, 95% CI: 1.24-3.74), PFDA (OR: 1.61, 95% CI: 1.10-2.44), PFUdA (OR: 1.71, 95% CI: 1.12-2.62), and PFDoA (OR: 1.34, 95% CI: 1.00-1.81). When the PFAS concentrations were categorized into three groups by tertiles, the highest tertiles of PFOS, PFOA, PFNA, PFDA, PFDoA, and PFTrDA had a statistically significant increase in the risk of high 1 h-PG concentrations compared with the lowest tertiles. No statistically significant association was observed between PFAS exposure and high FPG. CONCLUSION:PFAS exposure was associated with an increased risk of high 1 h-PG among pregnant women, but no such association was observed for FPG.
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Project description:There is collecting evidence suggesting that the process of chromatin remodeling such as changes in histone acetylation contribute to the formation of stress-related memory. Recently, the ventrolateral orbital cortex (VLO), a major subdivision of orbitofrontal cortex (OFC), was shown to be involved in antidepressant-like actions through epigenetic mechanisms. Here, we further investigated the effects of the histone deacetylase inhibitor (HDACi) valproic acid (VPA) on stress-related memory formation and the underlying molecular mechanisms by using the traditional two-day forced swimming test (FST). The results showed that VPA significantly increased the immobility time on day 2 when infused into the VLO before the initial forced swim stress on day 1. The learned immobility response to the stress was associated with increased phosphorylation of extracellular signal-regulated kinase (ERK) in VLO and hippocampus on the first day. The levels of phosphorylated ERK (phospho-ERK) in VLO and hippocampus were significantly decreased when retested 24 h later. The pretreatment with intra-VLO VPA infusion further reduced the activation of ERK on day 2 and day 7 compared with the saline controls. Moreover, the VPA infusion pretreatment also induced a significantly decreased BDNF level in the VLO on day 2, whereas no change was detected in the hippocampus. These findings suggest that VPA enhance the memories of emotionally stressful events and the ERK activity is implicated in stimulating adaptive and mnemonic processes in case the event would recur.
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