Large Amounts Of Glucose Research Articles

Glucose Metabolism Is Required for Oxidized LDL–Induced Macrophage Survival

Oxidized low-density lipoprotein (oxLDL) induces survival of colony stimulating factor-1 (CSF-1)-dependent macrophages in vitro. Because atherosclerotic lesion-associated macrophages take up large amounts of glucose, we investigated whether, and how, oxLDL promotes glucose uptake and how glucose metabolism regulates oxLDL-induced macrophage survival. OxLDL-induced macrophage survival required glucose metabolism. OxLDL stimulated 2 phases of glucose uptake, namely acute and chronic, which required PI3K but not MEK1/2 activity. PI3K appeared to regulate glucose transport via glucose transporter affinity and/or mobilization. OxLDL also maintained levels of the prosurvival proteins, Bcl-2 and Bcl-x(L), after CSF-1 had been removed through a combination of mechanisms including transcription, translation, and protein stabilization. Significantly, inhibition of glucose metabolism reduced Bcl-2 and Bcl-x(L) protein levels. MEK1/2 and PI3K activities were also required for oxLDL-induced Bcl-2 and Bcl-x(L) mRNA upregulation. These results suggest that oxLDL enhances macrophage survival in the absence of CSF-1 by inducing PI3K-dependent glucose uptake, which is metabolized to maintain Bcl-2 and Bcl-x(L) protein levels.

A 48-year-old man with uncontrolled diabetes

His type 2 diabetes has been well controlled for 6 years. Now, his blood sugar levels have been rising for the past week, and he has large amounts of glucose and ketones in the urine. What has happened?

Isomerization of Lactose-Derived Oligosaccharides: A Case Study Using Sodium Aluminate

Galactooligosaccharides (GOS) obtained during the enzymatic hydrolysis of lactose contain large amounts of glucose, galactose, and unreacted lactose, which do not have prebiotic properties and increase the calorific value of the product. In this work, the isomerization of the GOS mixture by the action of sodium aluminate has been studied. During the reaction, lactose, glucose, and galactose were isomerized to lactulose, fructose, and tagatose, respectively, and in addition allolactose, 6-galactobiose, and 6'-galactosyl-lactose were also converted to the corresponding keto-sugars. The effect of time, temperature, and aluminate/initial lactose ratio has been studied. After 9 h at 40 degrees C and molar ratio aluminate/lactose 3:1, the isomerization yield was >60%, and the amount of final carbohydrates was close to 90% of the initial product. This process considerably decreases the amount of lactose, glucose, and galactose.

La TEP au 18F-FDG dans la pathologie inflammatoire et infectieuse : intestinale, prothétique, fibrose, sarcoïdose, tuberculose…

Nuclear medicine plays an important role in the evaluation of infection and inflammation. A variety of diagnostic methods are available for imaging this inflammation and infection, most notably computed tomography, 68Ga scintigraphy or radionuclide labeled leucocytes. Fluorine 18 fluorodeoxyglucose ( 18F-FDG) is a readily available radiotracer that offers rapid, exquisitely sensitive high-resolution images by positron emission tomography (PET). Inflammation can be acute or chronic, the former showing predominantly neutrophilic granulocyte infiltrates, whereas in the latter, macrophages predominate. FDG uptake in infection is based on the fact that mononuclear cells and granulocytes use large quantities of glucose by way of the hexose monophosphate shunts. 18F-FDG PET accurately helps diagnose spinal osteomyelitis, diabetic foot and in inflammatory conditions such as sarcoidosis and tuberculosis.(it appears to be useful for defining the extent of disease and monitoring response to treatment). 18F-FDG PET can also help localize the source of fever of undetermined origin, thereby guiding additional testing. 18F-FDG PET may be of limited usefulness in postoperative patients and in patients with a failed joint prosthesis or bowel inflammatory disease. In this review, we will focus on the role of 18F-FDG PET in the management of patients with inflammation or suspected or confirmed infection.

Unlocking the Energy Dynamics of Executive Functioning: Linking Executive Functioning to Brain Glycogen.

Past work suggests that executive functioning relies on glucose as a depletable energy, such that executive functioning uses a relatively large amount of glucose and is impaired when glucose is low. Glucose from the bloodstream is one energy source for the brain, and glucose stored in the brain as glycogen is another. A review of the literature on glycogen suggests that executive functioning uses it in much the same way as glucose, such that executive functioning uses glycogen and is impaired when glycogen is low. Findings on stress, physical persistence, glucose tolerance, diabetes, sleep, heat, and other topics provide general support for this view.

Hypoxic preconditioning up-regulates glucose transport activity and glucose transporter (GLUT1 and GLUT3) gene expression after acute anoxic exposure in the cultured rat hippocampal neurons and astrocytes

Hypoxic preconditioning has been shown to increase the hypoxic tolerance of brain neurons. However, the mechanism underlying the increased hypoxic tolerance has not been well elucidated. Since anaerobic glycolysis is the only pathway for a vertebrate cell to produce energy under anoxic conditions, which needs a large amount of glucose, we hypothesize that glucose transport, the rate-limiting step for glucose metabolism, plays a critical role in the hypoxic tolerance induced by hypoxic preconditioning. In this study, the effects of hypoxic preconditioning on glucose transport activity and the gene expression of two major forms of glucose transporters (GLUT1 and GLUT3) in the brain were investigated in cultured rat hippocampal neurons and astrocytes. The neuronal and astroglial cultures were preconditioned for 6 days by intermittently exposing the cells to sublethal hypoxic gas mixture (1% O 2/10% CO 2/89% N 2) for 20 min each day. 24 h after the last hypoxic exposure, the cells were exposed to a lethal anoxic gas mixture (10% CO 2/90% N 2) for 6 h and the uptake rate of [ 3H] 2-deoxyglucose (2-DG) and the levels of GLUT1 and GLUT3 glucose transporter mRNAs in the cells were examined immediately after anoxic exposure. The neurons and astrocytes preconditioned with hypoxia showed higher 2-DG uptake rates than the non-preconditioned cells. Compatible with the change in 2-DG uptake, hypoxic preconditioning also increased GLUT1 mRNA levels in the astrocytes and GLUT1 and GLUT3 mRNA levels in the neurons. The neurons preconditioned by hypoxia displayed increased anoxic tolerance. However, when glucose uptake in the neurons was blocked by cytochalasin B, the anoxic tolerance was almost abolished. These results suggest that glucose transport is critical to neuronal survival during anoxic exposure and the increased glucose transport activity is probably one of the important mechanisms for the enhanced hypoxic tolerance induced by hypoxic preconditioning.

Toward a Physiology of Dual-Process Reasoning and Judgment: Lemonade, Willpower, and Expensive Rule-Based Analysis

This experiment used the attraction effect to test the hypothesis that ingestion of sugar can reduce reliance on intuitive, heuristic-based decision making. In the attraction effect, a difficult choice between two options is swayed by the presence of a seemingly irrelevant "decoy" option. We replicated this effect and the finding that the effect increases when people have depleted their mental resources performing a previous self-control task. Our hypothesis was based on the assumption that effortful processes require and consume relatively large amounts of glucose (brain fuel), and that this use of glucose is why people use heuristic strategies after exerting self-control. Before performing any tasks, some participants drank lemonade sweetened with sugar, which restores blood glucose, whereas others drank lemonade containing a sugar substitute. Only lemonade with sugar reduced the attraction effect. These results show one way in which the body (blood glucose) interacts with the mind (self-control and reliance on heuristics).

The Physiology of Willpower: Linking Blood Glucose to Self-Control

Past research indicates that self-control relies on some sort of limited energy source. This review suggests that blood glucose is one important part of the energy source of self-control. Acts of self-control deplete relatively large amounts of glucose. Self-control failures are more likely when glucose is low or cannot be mobilized effectively to the brain (i.e., when insulin is low or insensitive). Restoring glucose to a sufficient level typically improves self-control. Numerous self-control behaviors fit this pattern, including controlling attention, regulating emotions, quitting smoking, coping with stress, resisting impulsivity, and refraining from criminal and aggressive behavior. Alcohol reduces glucose throughout the brain and body and likewise impairs many forms of self-control. Furthermore, self-control failure is most likely during times of the day when glucose is used least effectively. Self-control thus appears highly susceptible to glucose. Self-control benefits numerous social and interpersonal processes. Glucose might therefore be related to a broad range of social behavior.

Targeting mitochondria in the treatment of human cancer: a coordinated attack against cancer cell energy metabolism and signalling

Mitochondria have major roles in bioenergetics and vital signalling of the mammalian cell. Consequently, these organelles have been implicated in the process of carcinogenesis, which includes alterations of cellular metabolism and cell death pathways. Multiple molecular routes of malignant transformation appear to result in the common ability of many tumours to take up large amounts of glucose. This metabolic twist has been explained by phenomena such as aerobic glycolysis and impaired mitochondrial function, and is linked to tumour growth potential via major cellular signalling pathways. This paper reviews the literature on central mechanisms through which energy metabolism merges with growth, proliferation and death signalling, which tend to include mitochondria at some level. These processes can potentially be targeted by pharmacological agents for therapeutic and chemosensitising purposes.

OeMST2 Encodes a Monosaccharide Transporter Expressed throughout Olive Fruit Maturation

In olive fruits, sugars are the main soluble components providing energy and acting as precursors for olive oil biosynthesis. Large quantities of glucose, fructose and galactose are often found in olive pulp. To analyze sugar transport processes in Olea europaea, a cDNA encoding a monosaccharide transporter, designated OeMST2 (Olea europaea monosaccharide transporter 2) was cloned. An open reading frame of 1,569 bp codes for a protein of 523 amino acids and a calculated molecular weight of 57.6 kDa. The protein is homologous to other sugar transporters identified so far in higher plants. Expression of this cDNA in an hxt-null Saccharomyces cerevisiae strain deficient in glucose transport restored its capacity to grow on and to transport glucose. The encoded protein showed high affinity for D-glucose (K(m), 25 microM) and was also able to recognize D-galactose and the analogs 3-O-methyl-D-glucose and 2-deoxy-D-glucose, but not D-fructose, D-arabinose, sucrose or D-mannitol. Maximal transport activity was high at acidic pH (5.0), and the initial D-[(14)C]glucose uptake rates were strongly inhibited by the protonophore carbonyl cyanide m-chlorophenylhydrazone, confirming that OeMST2 is a H(+)/monosaccharide transporter. The expression of OeMST2 was studied during the ripening process. Transcript levels increased during fruit maturation, suggesting that OeMST2 takes part in the massive accumulation of monosaccharides in olive fruits. Monosaccharide:H(+) transport system activity and OeMST2 expression were negatively regulated by glucose in suspension-cultured cells. Glucose-mediated OeMST2 repression was impaired by mannoheptulose, suggesting the involvement of a hexokinase-dependent signaling pathway.

Effects of CAPD on hepatosteatosis and lipid profile

Sir, Non-infectious complications that may occur in patients on continuous peritoneal dialysis (CAPD) include hernia formation, leaks (including hydrothorax or pleuroperitoneal leaks), local oedema, back pain and gastrointestinal prob- lems, such as gastro-oesophageal reflux and delayed gastric emptying. CAPD is associated with a number of metabolic abnormalities. These include lipid abnormalities, most commonly hypertriglyceridaemia, increased very low-density lipoprotein (VLDL) cholesterol and decreased high-density lipoprotein (HDL)-cholesterol levels; carbohydrate abnorm- alities, a result of the absorption of large quantities of glucose; protein losses, consisting of albumin and amino acid losses; and a propensity to obesity. In our study, we investigated whether patients on CAPD had increased tendency to fatty liver and changes of lipid profile. We studied 22 patients with end-stage renal disease (ESRD) on chronic peritoneal dialysis: 14 females and eight males with a mean age of 38.8±15.5 (16-71) years. We measured the height and dry weight of all patients. Body mass index (BMI) was calculated by dividing the weight (kg) by height squared (m 2 ). At the time of sampling, no patients had diabetes mellitus. No patient was hepatitis B virus (HBV) and anti-hepatitis C virus (HCV) positive. The patients had no history of significant alcohol consumption. In all patients, serum fasting glucose, urea, creatinine, albumin, ALT, AST, cholesterol, triglyceride, HDL-cholesterol, low- density lipoprotein (LDL)-cholesterol and VLDL-cholesterol were measured, and liver ultrasonography was performed by the same radiologist. Grade 1 fatty liver was revealed in nine patients (40.9%). Patients with hepatosteatosis detected by ultrasound were compared with patients without hepatosteatosis. No differences were observed in terms of blood glucose, total cholesterol, triglyceride, HDL, LDL, VLDL, ALT, AST and albumin levels (respectively P ¼ 0.23, 0.53, 0.74, 0.86, 0.91, 0.57, 0.27, 0.20 and 0.85) (Table 1). Oreopoulos et al. reported alterations in the morphology of the superficial liver lobuli of dialysed rats (1). In several studies, it was described that hepatic subcapsular steatosis was specific to diabetic CAPD patients on intraperitoneal insulin treatment (2-4). In our study, the follow-up time is relatively shorter (mean 22.4± 14.3, 3-72 months). Further long-term studies are needed in larger series in order to elucidate better the relationship of hepatosteatosis and lipid profile in CAPD patients. As far as we know, there is no similar study in the literature on the effects of CAPD on hepatosteatosis.

Glucose localization in maize ovaries when kernel number decreases at low water potential and sucrose is fed to the stems.

Around the time of anthesis, young ovary development in maize (Zea mays) is vulnerable to 2 or 3 d of water deficits that inhibit photosynthesis. Abortion can result, and fewer kernels are produced. A breakdown of stored ovary starch is associated with the abortion and was investigated in the present study by localizing the breakdown product glucose in the ovaries. Ovary glucose was localized with fluorescent Resorufin. Insoluble invertase was localized in vivo and soluble invertase in situ. Sucrose was infused into the stems to vary the sugar flux to the ovaries. At high water potential (high Psi(w)), photosynthesis was rapid in the parent. The upper pedicel of the ovaries had a high activity of insoluble acid invertase and a large amount of glucose and starch. Because the invertase was wall-bound, sucrose hydrolysis appeared to occur in the pedicel apoplast. Soluble invertase was undetected inside the pedicel cells but was present in the nucellus cells where low concentrations of glucose occurred. This created a glucose gradient between pedicel and nucellus that favoured glucose uptake by the developing ovary. At low Psi(w), photosynthesis was inhibited, pedicel glucose and starch were depleted, the glucose gradient became negligible, and abortion occurred. When sucrose was fed, glucose, starch and the glucose gradient were maintained somewhat and were normally distributed in the ovaries. Abortion was diminished. The apoplast hydrolysis of sucrose unloaded from phloem is similar to that described by others during later development when embryo and endosperm are present and separated from the parent by an apoplast. The disappearance of the glucose gradient at low Psi(w) may have inhibited glucose movement into the ovary. The low glucose in the ovaries may have a role in the abortion response.

Expression of a yeast-derived invertase in companion cells results in long-distance transport of a trisaccharide in an apoplastic loader and influences sucrose transport.

Companion cell-specific expression of a cytosolic invertase from yeast ( Saccharomyces cerevisiae) was used as a tool to synthesise oligosaccharides in the sieve element/companion cell complex and study whether oligosaccharides could be transported in the phloem of an apoplastically loading species. Potato ( Solanum tuberosum L.) plants expressing the invertase under the control of the Agrobacterium tumefaciens rolC promoter produced the trisaccharide 6-kestose in leaves, which was transported via the phloem and accumulated in tubers of transgenic plants. In graft experiments with rolC invertase plants as scion and wild-type rootstocks, 6-kestose accumulated in tubers to levels comparable to sucrose. This shows that long-distance transport of oligosaccharides is possible in apoplastically loading plants, which normally transport only sucrose. The additional transport route for assimilates neither led to elevated photosynthetic activity nor to increased tuber yield. Enhanced sucrose turnover in companion cells caused large amounts of glucose and fructose to be exuded from leaf petioles, and elevated levels of sucrose were detected in phloem exudates. While the latter indicates a higher capacity for sucrose loading into the phloem due to increased metabolic activity of companion cells, the massive release of hexoses catalysed by the invertase seemed to interfere with assimilate delivery to sink organs.

Cold exposure induces tissue-specific modulation of the insulin-signalling pathway in Rattus norvegicus.

Cold exposure provides a reproducible model of improved glucose turnover accompanied by reduced steady state and glucose-induced insulin levels. In the present report we performed immunoprecipitation and immunoblot studies to evaluate the initial and intermediate steps of the insulin-signalling pathway in white and brown adipose tissues, liver and skeletal muscle of rats exposed to cold. Basal and glucose-induced insulin secretion were significantly impaired, while glucose clearance rates during a glucose tolerance test and the constant for glucose decay during a 15 min insulin tolerance test were increased, indicating a significantly improved glucose turnover and insulin sensitivity in rats exposed to cold. Evaluation of protein levels and insulin-induced tyrosine (insulin receptor, insulin receptor substrates (IRS)-1 and -2, ERK (extracellular signal-related kinase)) or serine (Akt; protein kinase B) phosphorylation of proteins of the insulin signalling cascade revealed a tissue-specific pattern of regulation of the molecular events triggered by insulin such that in white adipose tissue and skeletal muscle an impaired molecular response to insulin was detected, while in brown adipose tissue an enhanced response to insulin was evident. In muscle and white and brown adipose tissues, increased 2-deoxy-D-glucose (2-DG) uptake was detected. Thus, during cold exposure there is a tissue-specific regulation of the insulin-signalling pathway, which seems to favour heat-producing brown adipose tissue. Nevertheless, muscle and white adipose tissue are able to take up large amounts of glucose, even in the face of an apparent molecular resistance to insulin.

DNA microarray analysis of the expression of the genes encoding the major enzymes in ethanol production during glucose and xylose co-fermentation by metabolically engineered Saccharomyces yeast

Lignocellulosic biomass, which contains large amounts of glucose and xylose, is the new ideal feedstock for ethanol production used as renewable liquid fuel for transportation. The naturally occurring Saccharomyces yeasts traditionally used for industrial ethanol production are unable to ferment xylose. We have successfully developed genetically engineered Saccharomyces yeasts that can effectively co-ferment both glucose and xylose simultaneously to ethanol. Our engineered yeast contains three xylose metabolizing genes, the xylose reductase (XR), xylitol dehydrogenase (XD) and xylulokinase (XK) genes, fused to glycolytic promoters, on high copy plasmids or integrated into the yeast chromosome in multiple copies. Although our glucose/xylose co-fermenting yeasts are currently the most effective yeast for producing ethanol from cellulosic biomass, they still utilize glucose more efficiently than xylose. We believe that carefully analyzing gene expression during co-fermentation of glucose and xylose to ethanol, using our genetically modified strains, will reveal ways to optimize xylose fermentation. In this paper, we report our results on analyzing the expression of genes in the glycolitic and alcoholic fermentation pathways using microarray technology. We also report the results on the analysis of the activities of the selected enzymes for ethanol production during co-fermentation of glucose and xylose to ethanol by one of our effective glucose/xylose co-fermenting yeasts 424A(LNH-ST).

Electron flow to photosystem I from stromal reductants in vivo: the size of the pool of stromal reductants controls the rate of electron donation to both rapidly and slowly reducing photosystem I units.

Electron donation from stromal reductants to photosystem I (PSI) was studied using the kinetics of P700(+) (the oxidized primary donor of PSI) reduction in the dark after irradiation of barley ( Hordeum vulgare L.) leaves. The leaves were treated with diuron and methyl viologen to abolish both the electron flow from PSII and PSI-driven cyclic electron transport. The redox state of P700 was monitored using the absorbance changes at 830 nm (Delta A(830)). Two exponentially decaying components with half-times of about 3 s (the slow component) and about 0.6 s (the fast one) were distinguished in the kinetic curves of Delta A(830) relaxation after a 1-s pulse of far-red light. The complex kinetics of P700(+) reduction thus manifested two types of PSI unit differing in the rate of electron input from stromal reductants. The rates of both kinetic components assayed after 1-s pulses were increased about 20-fold by a short (2-5 min) heat-pretreatment of leaves, indicating the accelerated input of electrons to both types of PSI unit. The increased rates of electron flow to P700(+) were even observed 1.5 h after the action of heat had been completed. Both kinetic components were dramatically slowed down upon irradiation of heat-treated leaves for 20-30 s. Their rates were restored after a short (20-30 s) period of darkness. A 5-min leaf exposure at 38 degrees C was sufficient to stimulate by severalfold the reduction of P700(+) pre-oxidized by a brief light pulse. In contrast, the acceleration of P700(+) reduction after a 1-min irradiation was observed only if leaves were subjected to temperatures above 40 degrees C. Neither heat treatment of leaves nor light-dark modulations in the rates of the fast and the slow components of P700(+) dark reduction influenced the relative magnitudes of the two kinetic components, providing strong additional evidence in favor of two distinct types of PSI existing per se in barley leaves. The key role in the control of the activity of electron donation to P700(+) in both rapidly and slowly reducing PSI units was attributed to the amount of stromal reductants available for P700(+) reduction. The latter was expected to be reduced under illumination in the presence of methyl viologen, while increased again in the dark. The regeneration of the pool of stromal reductants in the dark was likely provided by starch breakdown within the chloroplast stroma, but not by import of reducing equivalents from the cytosol. This was evidenced by much lower rates, compared with 1-h dark-adapted leaves, of dark reduction of both components of P700(+) in leaves stored for 24 h in the dark and thus depleted of starch but containing large amounts of glucose, the respiratory substrate.

Roles of glucose and acetate as carbon sources inl-histidine production withBrevibacterium flavum FERM1564 revealed by metabolic flux analysis

The metabolic flux pattern forl-histidine production was analyzed when glucose and/or acetate were used as carbon sources. Totall-histidine production was enhanced when mixed substrate (glucose and acetate) was used, compared with that when either glucose or acetate was used as the sole carbon source. Theoretical maximum carbon fluxes through the main pathways forl-histidine production, cell growth, and ATP consumption for cell maintenance were obtained by the linear programming (LP) method. By comparison of the theoretical maximum carbon fluxes with actual ones, it was found that a large amount of glucose was actually used for maintenance of cell viability. On the other hand, acetate was used for cell growth. After depletion of acetate in the mixed substrate culture, the flux for glucose tol-histidine synthesis was markedly enhanced. A strategy for effectivel-histidine production using both carbon sources was proposed.

Grand Larceny: Oxidant corrupts protein by filching crucial atom (Oxidative damage; Cardiovascular disease)

A new study reveals how oxidants undermine an enzyme that helps keep our blood vessels open and clear of clots. These molecular vandals steal an atom of zinc that helps hold the protein together--not only harming the enzyme in the process but also stimulating the production of more of the cell-wrecking chemicals. By gnawing on proteins and other molecules, oxidants drive heart disease, diabetes, and aging--or so the theory goes (see "The Two Faces of Oxygen" ). These hungry molecules, such as superoxide and peroxynitrite, are spawned in the normal course of metabolism. How they could wreak so much destruction is an enigma, considering that only 1 in 1000 to 1 in 10,000 amino acids in a cell show signs of oxidative wounds, says Jay Heinecke of Washington University in St. Louis, Missouri, an authority on these baneful molecules. Zou and colleagues uncovered the effects of oxidants on one of the body's key enzymes, nitric oxide synthase, which comprises two identical halves coupled by a bridge containing zinc and sulfur. True to its name, nitric oxide synthase makes nitric oxide, a versatile and vital signaling molecule that opens blood vessels and inhibits clot formation. The researchers exposed nitric oxide synthase to peroxynitrite and tracked the enzyme's response. Even small amounts of peroxynitrite broke the protein in half by swiping zinc from the bridge. The same changes occurred when the researchers treated the enzyme with a molecule that locks up zinc, confirming that the parting of the protein resulted from removing the metal. What's more, cells bathed in abnormally large amounts of glucose and cells from diabetic mice showed the same breakup of nitric oxide synthase--which suggests that damage to the enzyme might contribute to diabetes. Broken nitric oxide synthase doesn't simply fail to produce nitric oxide. Oxidation brings out the enzyme's alter ego, which instead makes superoxide. This promiscuous oxidant can react with nitric oxide to produce yet more peroxynitrite--setting off a runaway process of peroxynitrite formation. Although previous work had suggested that nitric oxide synthase might spawn peroxynitrite, this study is the first to clarify the mechanism and to show how sensitive the enzyme is, even to low concentrations of the oxidant. Both consequences of oxidation might compromise health, says biochemist Ming-Hui Zou of Boston University School of Medicine. Reduced amounts of nitric oxide narrow blood vessels and spur clotting, which worsen cardiovascular disease. Peroxynitrite also attacks a molecule that prevents constriction of blood vessels, which might explain why the arteries of diabetics expand reluctantly, Zou adds. According to Heinecke, the results also back a nontraditional view of how oxidants wreak havoc. The conventional notion--that their attack cripples proteins--is hard to square with the rarity of oxidants in the body's cells. A more plausible idea, says Heinecke, is that oxidants pervert proteins instead of wrecking them: "You are damaging a protein in a way that produces a gain in function. It's doing something bad instead of something good." --Mitch Leslie M.-H. Zou, C. Shi, R. A. Cohen, Oxidation of the zinc-thiolate complex and uncoupling of endothelial nitric oxide synthase by peroxynitrite. J. Clin. Invest. 109 , 817-826 (2002). [Abstract] [Full Text]

No Take Backs: Mice that can't get rid of insulin develop signs of diabetes (Insulin resistance; Diabetes)

If the remnants of a meal aren't tidied, they can turn into a big mess, whether it's in your kitchen or your body. Insulin normally coordinates the cleanup of leftovers in the bloodstream. But cells can turn recalcitrant and ignore the hormone's directives. Researchers have blamed overproduction of insulin for this state, known as insulin resistance, which becomes increasingly common as people age and can lead to diabetes. But new work in mice suggests that ineptitude at getting rid of insulin after a sugar surge can also cause the trouble. Eat a Krispy Kreme doughnut, and feel your blood sugar soar. In response, the pancreas produces insulin, which tells muscle, fat, and liver cells to soak up the sweets. Insulin sets off a chain reaction when it attaches to a cell surface receptor. The receptor adds a phosphate group to other proteins, which enables them to prod cells to absorb sugar and store it. As sugar concentration in the blood falls, liver cells take up insulin to shut off this response. Previous work hinted at a player involved in this insulin clearance pathway. Researchers had determined that a protein called CEACAM1 receives a phosphate group when cultured liver cells are treated with insulin and that cultured cells lacking CEACAM1 can't reabsorb the signaling molecule. But they didn't know whether CEACAM1 helps intact animals soak up insulin. To answer that question, Poy and colleagues engineered a mutant mouse whose liver cells produce a version of CEACAM1 that lacks the site where phosphate attaches. The creatures are chubbier and carry more tummy fat than control animals do; in addition, two to five times the normal amount of insulin courses through the mutants' blood. To find out whether the mice produce extra insulin or can't get rid of what they make, the team injected radioactively labeled insulin into the animals' tails. After 1 hour, the mutant mice retained two to three times as much insulin in their blood as wild-type mice did. These and other experiments suggest that CEACAM1-defective mice can't efficiently remove insulin from the bloodstream. The mutant mice also exhibit hallmarks of insulin resistance. They have abnormally large amounts of glucose in their blood and recover unusually slowly when the researchers inject them with the sugar. In addition, liver cells from mutant mice display fewer insulin receptors than do those from their wild-type siblings. Muscle and fat cells, however, retain their insulin sensitivity, indicating that the animals do not develop diabetes. Together, the results suggest that problems in insulin uptake can stimulate insulin resistance, although additional deficiencies are needed to trigger diabetes. The results are provocative, says cell biologist Morris Birnbaum of the University of Pennsylvania in Philadelphia. But he cautions that the experiments on mice are "a far cry from showing that this ever really happens in people, much less is related to human disease." The work suggests, however, that telling the cleaning crew to go home once the job is done might be good for your health. --R. John Davenport M. N. Poy, Y. Yang, K. Rezaei, M. A. Fernström, A. D. Lee, Y. Kido, S. K. Erickson, S. M. Najjar, CEACAM1 regulates insulin clearance in liver. Nature Genet. , 19 February 2002 [e-pub ahead of print]. [Abstract] [Full Text]

Quantitative Glucose Metabolism in Lactating Mink ( Mustela vison ) - Effects of Dietary Levels of Protein, Fat and Carbohydrates

Glucose metabolism was measured during two consecutive years, 4 weeks postpartum, in a total of 36 yearling female mink, fitted with jugular vein catheters and raising litters of six to seven kits. The dams were fed ad libitum from parturition on diets with different ratios of metabolizable energy (ME) derived from protein:fat:carbohydrates (experiment 1: 61:37:2, 46:37:17, 31:37:32; experiment 2: 61:38:1, 47:52:1, 33:66:1). After 3 h fasting the dams were fed 210 kJ ME of the experimental diets. Two hours postprandially a single dose of 50 w Ci U- 14 C- and 2- 3 H-labelled glucose was administered to each dam and blood samples were drawn 5, 10, 20, 30, 45 and 60 min after the tracer administration. Glucose turnover rates were 4-5% min -1 in all dams, and the approximate daily glucose flux was 12-17 g day -1 ; however, these were not significantly affected by dietary treatment. In conclusion, the mink is able both to synthesize large amounts of glucose de novo and to utilize high levels of dietary digestible carbohydrates, and thereby to tolerate large variations in dietary carbohydrate supply.