Gluconeogenesis: Biosynthesis of GLUCOSE from nonhexose or non-carbohydrate precursors, such as LACTATE; PYRUVATE; ALANINE; and GLYCEROL.Lactates: Salts or esters of LACTIC ACID containing the general formula CH3CHOHCOOR.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Phosphoenolpyruvate Carboxykinase (GTP): An enzyme of the lyase class that catalyzes the conversion of GTP and oxaloacetate to GDP, phosphoenolpyruvate, and carbon dioxide. This reaction is part of gluconeogenesis in the liver. The enzyme occurs in both the mitochondria and cytosol of mammalian liver. (From Dorland, 27th ed) EC 4.1.1.32.Phosphoenolpyruvate Carboxykinase (ATP): An enzyme of the lyase class that catalyzes the conversion of ATP and oxaloacetate to ADP, phosphoenolpyruvate, and carbon dioxide. The enzyme is found in some bacteria, yeast, and Trypanosoma, and is important for the photosynthetic assimilation of carbon dioxide in some plants. EC 4.1.1.49.Glucose-6-Phosphatase: An enzyme that catalyzes the conversion of D-glucose 6-phosphate and water to D-glucose and orthophosphate. EC 3.1.3.9.PyruvatesGlucose: A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.Glucagon: A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal GLUCAGON-LIKE PEPTIDES. Glucagon is secreted by PANCREATIC ALPHA CELLS and plays an important role in regulation of BLOOD GLUCOSE concentration, ketone metabolism, and several other biochemical and physiological processes. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1511)Dihydroxyacetone: A ketotriose compound. Its addition to blood preservation solutions results in better maintenance of 2,3-diphosphoglycerate levels during storage. It is readily phosphorylated to dihydroxyacetone phosphate by triokinase in erythrocytes. In combination with naphthoquinones it acts as a sunscreening agent.Glycogenolysis: The release of GLUCOSE from GLYCOGEN by GLYCOGEN PHOSPHORYLASE (phosphorolysis). The released glucose-1-phosphate is then converted to GLUCOSE-6-PHOSPHATE by PHOSPHOGLUCOMUTASE before entering GLYCOLYSIS. Glycogenolysis is stimulated by GLUCAGON or EPINEPHRINE via the activation of PHOSPHORYLASE KINASE.Pyruvic Acid: An intermediate compound in the metabolism of carbohydrates, proteins, and fats. In thiamine deficiency, its oxidation is retarded and it accumulates in the tissues, especially in nervous structures. (From Stedman, 26th ed)Ketone Bodies: The metabolic substances ACETONE; 3-HYDROXYBUTYRIC ACID; and acetoacetic acid (ACETOACETATES). They are produced in the liver and kidney during FATTY ACIDS oxidation and used as a source of energy by the heart, muscle and brain.Lactic Acid: A normal intermediate in the fermentation (oxidation, metabolism) of sugar. The concentrated form is used internally to prevent gastrointestinal fermentation. (From Stedman, 26th ed)Liver Glycogen: Glycogen stored in the liver. (Dorland, 28th ed)Deuterium Oxide: The isotopic compound of hydrogen of mass 2 (deuterium) with oxygen. (From Grant & Hackh's Chemical Dictionary, 5th ed) It is used to study mechanisms and rates of chemical or nuclear reactions, as well as biological processes.Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent.Fructose-Bisphosphatase: An enzyme that catalyzes the conversion of D-fructose 1,6-bisphosphate and water to D-fructose 6-phosphate and orthophosphate. EC 3.1.3.11.TriosesPyruvate Kinase: ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.Oxaloacetates: Derivatives of OXALOACETIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include a 2-keto-1,4-carboxy aliphatic structure.Pyruvate Carboxylase: A biotin-dependent enzyme belonging to the ligase family that catalyzes the addition of CARBON DIOXIDE to pyruvate. It is occurs in both plants and animals. Deficiency of this enzyme causes severe psychomotor retardation and ACIDOSIS, LACTIC in infants. EC 6.4.1.1.Starvation: Lengthy and continuous deprivation of food. (Stedman, 25th ed)GlycogenMethenamine: An anti-infective agent most commonly used in the treatment of urinary tract infections. Its anti-infective action derives from the slow release of formaldehyde by hydrolysis at acidic pH. (From Martindale, The Extra Pharmacopoeia, 30th ed, p173)Blood Glucose: Glucose in blood.Fasting: Abstaining from all food.Picolinic AcidsGlycolysis: A metabolic process that converts GLUCOSE into two molecules of PYRUVIC ACID through a series of enzymatic reactions. Energy generated by this process is conserved in two molecules of ATP. Glycolysis is the universal catabolic pathway for glucose, free glucose, or glucose derived from complex CARBOHYDRATES, such as GLYCOGEN and STARCH.Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases IMMUNITY, and provides energy for muscle tissue, BRAIN, and the CENTRAL NERVOUS SYSTEM.Citric Acid Cycle: A series of oxidative reactions in the breakdown of acetyl units derived from GLUCOSE; FATTY ACIDS; or AMINO ACIDS by means of tricarboxylic acid intermediates. The end products are CARBON DIOXIDE, water, and energy in the form of phosphate bonds.Acetoacetates: Salts and derivatives of acetoacetic acid.Hydroxybutyrates: Salts and esters of hydroxybutyric acid.Insulin: A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).Quinolinic AcidsAminooxyacetic Acid: A compound that inhibits aminobutyrate aminotransferase activity in vivo, thereby raising the level of gamma-aminobutyric acid in tissues.PhosphoenolpyruvateMalatesHepatocytes: The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.Perfusion: Treatment process involving the injection of fluid into an organ or tissue.Glutamine: A non-essential amino acid present abundantly throughout the body and is involved in many metabolic processes. It is synthesized from GLUTAMIC ACID and AMMONIA. It is the principal carrier of NITROGEN in the body and is an important energy source for many cells.Carbon Isotopes: Stable carbon atoms that have the same atomic number as the element carbon, but differ in atomic weight. C-13 is a stable carbon isotope.3-Hydroxybutyric Acid: BUTYRIC ACID substituted in the beta or 3 position. It is one of the ketone bodies produced in the liver.Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Hypoglycins: Methylene cyclopropyl alanine and congeners isolated from the unripe edible fruit of the AKEE plant (BLIGHIA SAPIDA). Hypoglycin B is the gamma-glutamyl congener of hypoglycin A. They are very toxic and teratogenic, causing a syndrome called Jamaican vomiting sickness that includes a fall in blood glucose due to the interference of FATTY ACIDS and LEUCINE metabolism which leads to VOMITING, liver damage, CONVULSIONS and DEATH.Fatty Acids, Nonesterified: FATTY ACIDS found in the plasma that are complexed with SERUM ALBUMIN for transport. These fatty acids are not in glycerol ester form.Transaldolase: An enzyme of the transferase class that catalyzes the reaction sedoheptulose 7-phosphate and D-glyceraldehyde 3-phosphate to yield D-erythrose 4-phosphate and D-fructose phosphate in the PENTOSE PHOSPHATE PATHWAY. (Dorland, 27th ed) EC 2.2.1.2.Propionates: Derivatives of propionic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxyethane structure.Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus.Fructosediphosphates: Diphosphoric acid esters of fructose. The fructose-1,6- diphosphate isomer is most prevalent. It is an important intermediate in the glycolysis process.Carbohydrate Metabolism: Cellular processes in biosynthesis (anabolism) and degradation (catabolism) of CARBOHYDRATES.Radioisotope Dilution Technique: Method for assessing flow through a system by injection of a known quantity of radionuclide into the system and monitoring its concentration over time at a specific point in the system. (From Dorland, 28th ed)Glyceraldehyde 3-Phosphate: An aldotriose which is an important intermediate in glycolysis and in tryptophan biosynthesis.Fructose: A monosaccharide in sweet fruits and honey that is soluble in water, alcohol, or ether. It is used as a preservative and an intravenous infusion in parenteral feeding.Mitochondria, Liver: Mitochondria in hepatocytes. As in all mitochondria, there are an outer membrane and an inner membrane, together creating two separate mitochondrial compartments: the internal matrix space and a much narrower intermembrane space. In the liver mitochondrion, an estimated 67% of the total mitochondrial proteins is located in the matrix. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p343-4)Phosphofructokinase-1: An allosteric enzyme that regulates glycolysis by catalyzing the transfer of a phosphate group from ATP to fructose-6-phosphate to yield fructose-1,6-bisphosphate. D-tagatose- 6-phosphate and sedoheptulose-7-phosphate also are acceptors. UTP, CTP, and ITP also are donors. In human phosphofructokinase-1, three types of subunits have been identified. They are PHOSPHOFRUCTOKINASE-1, MUSCLE TYPE; PHOSPHOFRUCTOKINASE-1, LIVER TYPE; and PHOSPHOFRUCTOKINASE-1, TYPE C; found in platelets, brain, and other tissues.Glucokinase: A group of enzymes that catalyzes the conversion of ATP and D-glucose to ADP and D-glucose 6-phosphate. They are found in invertebrates and microorganisms, and are highly specific for glucose. (Enzyme Nomenclature, 1992) EC 2.7.1.2.Adenine NucleotidesCarbon Radioisotopes: Unstable isotopes of carbon that decay or disintegrate emitting radiation. C atoms with atomic weights 10, 11, and 14-16 are radioactive carbon isotopes.Hyperglycemia: Abnormally high BLOOD GLUCOSE level.Glucose-6-Phosphate: An ester of glucose with phosphoric acid, made in the course of glucose metabolism by mammalian and other cells. It is a normal constituent of resting muscle and probably is in constant equilibrium with fructose-6-phosphate. (Stedman, 26th ed)Ketoglutaric Acids: A family of compounds containing an oxo group with the general structure of 1,5-pentanedioic acid. (From Lehninger, Principles of Biochemistry, 1982, p442)Oleic Acids: A group of fatty acids that contain 18 carbon atoms and a double bond at the omega 9 carbon.Epinephrine: The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.Radioactive Tracers: Radioactive substances added in minute amounts to the reacting elements or compounds in a chemical process and traced through the process by appropriate detection methods, e.g., Geiger counter. Compounds containing tracers are often said to be tagged or labeled. (Hawley's Condensed Chemical Dictionary, 12th ed)Hypoglycemia: A syndrome of abnormally low BLOOD GLUCOSE level. Clinical hypoglycemia has diverse etiologies. Severe hypoglycemia eventually lead to glucose deprivation of the CENTRAL NERVOUS SYSTEM resulting in HUNGER; SWEATING; PARESTHESIA; impaired mental function; SEIZURES; COMA; and even DEATH.Metformin: A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289)Caprylates: Derivatives of caprylic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain a carboxy terminated eight carbon aliphatic structure.Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.Kinetics: The rate dynamics in chemical or physical systems.Glutamates: Derivatives of GLUTAMIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure.Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals.Energy Metabolism: The chemical reactions involved in the production and utilization of various forms of energy in cells.Hypoglycemic Agents: Substances which lower blood glucose levels.Food Deprivation: The withholding of food in a structured experimental situation.Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).Urea: A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids.Fatty Acids: Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed)CitratesKidney Cortex: The outer zone of the KIDNEY, beneath the capsule, consisting of KIDNEY GLOMERULUS; KIDNEY TUBULES, DISTAL; and KIDNEY TUBULES, PROXIMAL.Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as AMMONIUM HYDROXIDE.Fructose-Bisphosphate Aldolase: An enzyme of the lyase class that catalyzes the cleavage of fructose 1,6-biphosphate to form dihydroxyacetone phosphate and glyceraldehyde 3-phosphate. The enzyme also acts on (3S,4R)-ketose 1-phosphates. The yeast and bacterial enzymes are zinc proteins. (Enzyme Nomenclature, 1992) E.C. 4.1.2.13.GlyoxylatesHep G2 Cells: A human liver tumor cell line used to study a variety of liver-specific metabolic functions.Oxymetazoline: A direct acting sympathomimetic used as a vasoconstrictor to relieve nasal congestion. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1251)Glycerol Kinase: An enzyme that catalyzes the formation of glycerol 3-phosphate from ATP and glycerol. Dihydroxyacetone and L-glyceraldehyde can also act as acceptors; UTP and, in the case of the yeast enzyme, ITP and GTP can act as donors. It provides a way for glycerol derived from fats or glycerides to enter the glycolytic pathway. EC 2.7.1.30.Insulin Resistance: Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS.Oxygen Consumption: The rate at which oxygen is used by a tissue; microliters of oxygen STPD used per milligram of tissue per hour; the rate at which oxygen enters the blood from alveolar gas, equal in the steady state to the consumption of oxygen by tissue metabolism throughout the body. (Stedman, 25th ed, p346)KetonesAcetates: Derivatives of ACETIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxymethane structure.Carbon: A nonmetallic element with atomic symbol C, atomic number 6, and atomic weight [12.0096; 12.0116]. It may occur as several different allotropes including DIAMOND; CHARCOAL; and GRAPHITE; and as SOOT from incompletely burned fuel.Glycogen Phosphorylase: An enzyme that catalyzes the degradation of GLYCOGEN in animals by releasing glucose-1-phosphate from the terminal alpha-1,4-glycosidic bond. This enzyme exists in two forms: an active phosphorylated form ( PHOSPHORYLASE A) and an inactive un-phosphorylated form (PHOSPHORYLASE B). Both a and b forms of phosphorylase exist as homodimers. In mammals, the major isozymes of glycogen phosphorylase are found in muscle, liver and brain tissue.C-Peptide: The middle segment of proinsulin that is between the N-terminal B-chain and the C-terminal A-chain. It is a pancreatic peptide of about 31 residues, depending on the species. Upon proteolytic cleavage of proinsulin, equimolar INSULIN and C-peptide are released. C-peptide immunoassay has been used to assess pancreatic beta cell function in diabetic patients with circulating insulin antibodies or exogenous insulin. Half-life of C-peptide is 30 min, almost 8 times that of insulin.Diabetes Mellitus, Type 2: A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING).Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.

Role of glutamine in human carbohydrate metabolism in kidney and other tissues. (1/1508)

Glutamine is the most abundant amino acid in the human body and is involved in more metabolic processes than any other amino acid. Until recently, the understanding of many aspects of glutamine metabolism was based on animal and in vitro data. However, recent studies using isotopic and balance techniques have greatly advanced the understanding of glutamine metabolism in humans and its role in glucose metabolism in the kidney and other tissues. There is now evidence that in postabsorptive humans, glutamine is an important glucose precursor and makes a significant contribution to the addition of new carbon to the glucose carbon pool. The importance of alanine for gluconeogenesis, viewed in terms of the addition of new carbons, is less than previously assumed. It appears that glutamine is predominantly a renal gluconeogenic substrate, whereas alanine gluconeogenesis is essentially confined to the liver. As shown recently, renal gluconeogenesis contributes 20 to 25% to whole-body glucose production. Moreover, glutamine has been shown not only to stimulate net muscle glycogen storage but also to stimulate gluconeogenesis in normal humans. Finally, in humans with type II diabetes, conversion of glutamine to glucose is increased (more so than that of alanine). The available evidence on the hormonal regulation of glutamine gluconeogenesis in kidney and liver and its alterations under pathological conditions are discussed.  (+info)

Inactivation of the winged helix transcription factor HNF3alpha affects glucose homeostasis and islet glucagon gene expression in vivo. (2/1508)

Mice homozygous for a null mutation in the winged helix transcription factor HNF3alpha showed severe postnatal growth retardation followed by death between P2 and P12. Homozygous mutant mice were hypoglycemic despite unchanged expression of HNF3 target genes involved in hepatic gluconeogenesis. Whereas insulin and corticosteroid levels were altered as expected, plasma glucagon was reduced markedly in the mutant animals despite the hypoglycemia that should be expected to increase glucagon levels. This correlated with a 70% reduction in pancreatic proglucagon gene expression. We also showed that HNF3alpha could bind to and transactivate the proglucagon gene promoter. These observations invoke a central role for HNF3alpha in the regulatory control of islet genes essential for glucose homeostasis in vivo.  (+info)

Contributions of net hepatic glycogenolysis and gluconeogenesis to glucose production in cirrhosis. (3/1508)

Net hepatic glycogenolysis and gluconeogenesis were examined in normal (n = 4) and cirrhotic (n = 8) subjects using two independent methods [13C nuclear magnetic resonance spectroscopy (NMR) and a 2H2O method]. Rates of net hepatic glycogenolysis were calculated by the change in hepatic glycogen content before ( approximately 11:00 PM) and after ( approximately 7:00 AM) an overnight fast using 13C NMR and magnetic resonance imaging. Gluconeogenesis was calculated as the difference between the rates of glucose production determined with an infusion of [6,6-2H2]glucose and net hepatic glycogenolysis. In addition, the contribution of gluconeogenesis to glucose production was determined by the 2H enrichment in C-5/C-2 of blood glucose after intake of 2H2O (5 ml/kg body water). Plasma levels of total and free insulin-like growth factor I (IGF-I) and IGF-I binding proteins-1 and -3 were significantly decreased in the cirrhotic subjects (P < 0.01 vs. controls). Postprandial hepatic glycogen concentrations were 34% lower in the cirrhotic subjects (P = 0.007). Rates of glucose production were similar between the cirrhotic and healthy subjects [9.0 +/- 0.9 and 10.0 +/- 0.8 micromol. kg body wt-1. min-1, respectively]. Net hepatic glycogenolysis was 3.5-fold lower in the cirrhotic subjects (P = 0.01) and accounted for only 13 +/- 6% of glucose production compared with 40 +/- 10% (P = 0.03) in the control subjects. Gluconeogenesis was markedly increased in the cirrhotic subjects and accounted for 87 +/- 6% of glucose production vs. controls: 60 +/- 10% (P = 0.03). Gluconeogenesis in the cirrhotic subjects, as determined from the 2H enrichment in glucose C-5/C-2, was also increased and accounted for 68 +/- 3% of glucose production compared with 54 +/- 2% (P = 0.02) in the control subjects. In conclusion, cirrhotic subjects have increased rates of gluconeogenesis and decreased rates of net hepatic glycogenolysis compared with control subjects. These alterations are likely important contributing factors to their altered carbohydrate metabolism.  (+info)

Enhanced gluconeogenesis and hepatic insulin resistance in insulin-like growth factor binding protein-1 transgenic mice. (4/1508)

Fasting hyperglycemia is observed in transgenic mice which overexpress insulin-like growth factor binding protein-1. In an attempt to understand the mechanisms underlying this observation we have examined glycogenolysis and gluconeogenesis in isolated hepatocytes from wild-type and transgenic mice. Glucose production from pyruvate was significantly less responsive to inhibition by insulin in hepatocytes from transgenic mice compared to hepatocytes from wild-type mice. Serum from transgenic mice resulted in more glucose production by hepatocytes than serum from wild-type mice. Serum alanine was increased while serum lactate was significantly reduced in transgenic mice compared to wild-type mice. Serum free fatty acids and beta-hydroxybutyrate were similar in both groups of mice. These data suggest that fasting hyperglycemia is due to enhanced gluconeogenesis, hepatic insulin resistance and increased serum gluconeogenic substrate in transgenic mice.  (+info)

Resistance to insulin's acute direct hepatic effect in suppressing steady-state glucose production in individuals with type 2 diabetes. (5/1508)

We and others have shown that insulin acutely suppresses glucose production in fasting nondiabetic humans and dogs, by both a direct hepatic effect and an indirect (extrahepatic) effect, and in diabetic dogs by an indirect effect alone. In type 2 diabetes, there is resistance to insulin's ability to suppress hepatic glucose production, but it has not previously been determined whether the resistance is primarily at the level of the hepatocyte or the peripheral tissues. To determine whether the diabetic state reduces the direct effect of insulin in humans, we studied nine patients with untreated type 2 diabetes who underwent three studies each, 4-6 weeks apart. 1) Portal study (POR): intravenous tolbutamide was infused for 3 h with calculation of pancreatic insulin secretion from peripheral plasma C-peptide. 2) Peripheral study (PER): equidose insulin was infused by peripheral vein. 3) Half-dose peripheral insulin study (1/2 PER): matched peripheral insulin levels with study 1. In all studies, glucose was clamped at euglycemia, glucose turnover was measured with the constant specific activity method, and 3-[3H]glucose was purified by high-performance liquid chromatography. Peripheral insulin was lower in POR versus PER but slightly higher in POR versus 1/2 PER, although most of the difference could be accounted for by higher proinsulin levels in POR (stimulated by tolbutamide). Calculated portal insulin was approximately 1.3-fold higher in POR versus PER and approximately 2.2-fold higher in POR versus 1/2 PER. In the final 30 min of the clamp, glucose production reached a lower steady-state level in PER than in POR (4.0 +/- 0.4 vs. 5.3 +/- 0.5 pmol(-1) x kg(-1) x min(-1), P < 0.05), despite the higher hepatic insulin level in POR. In contrast with our studies in nondiabetic individuals, glucose production was not more suppressed at steady state in POR versus 1/2 PER (5.3 +/- 0.4 micromol x kg(-1) x min(-1)), despite much higher hepatic insulin levels in POR. In conclusion, this is the first study in patients with type 2 diabetes to characterize insulin resistance to the acute direct suppressive effect of insulin on hepatic glucose production.  (+info)

Gluconeogenesis in very low birth weight infants receiving total parenteral nutrition. (6/1508)

Very low birth weight (VLBW) infants are dependent on total parenteral nutrition (TPN) to prevent hypoglycemia and provide a sufficient energy intake. However, diminished tolerance for parenteral glucose delivered at high rates frequently provokes hyperglycemia. We hypothesized that when their glucose supply is reduced to prevent hyperglycemia, VLBW infants can maintain normoglycemia via gluconeogenesis from glycerol and amino acids. Twenty infants born at 27 +/- 0.2 (mean +/- SE) gestational weeks and having a birth weight of 996 +/- 28 g, received lipids (1.6 +/- 0.1 mg x kg(-1) x min(-1)), protein (2.2 +/- 0.1 mg x kg(-1) x min(-1)), and glucose (3.1 +/- 0.1 mg x kg(-1) x min(-1) [17.1 +/- 0.2 micromol x kg(-1) x min(-1)]) parenterally over a period of 8-12 h on day 5.0 +/- 0.2 of life. Gluconeogenesis was estimated using [U-13C]glucose (n = 8) or [2-(13)C] glycerol (n = 6) and mass isotopomer distribution analysis (MIDA), or 2H2O (n = 6) and the rate of deuterium incorporation in carbon 6 of glucose. Blood glucose averaged 3.0 +/- 0.1 mmol/l; plasma glucose appearance rate (glucose Ra), 28.8 +/- 1.1 micromol x kg(-1) x min(-1); and glucose production rate (GPR), 10.7 +/- 1.0 micromol x kg(-1) x min(-1). The [U-13C]glucose and [2-(13)C]glycerol tracers provided similar estimates of gluconeogenesis, averaging 28 +/- 2 and 26 +/- 2% of glucose Ra and 72 +/- 5 and 73 +/- 9% of GPR, respectively. Glycerol contributed 64 +/- 5% of total gluconeogenesis. Gluconeogenesis measured by 2H2O, which does not include the contribution from glycerol, was comparable to the nonglycerol fraction of gluconeogenesis derived by the [2-(13)C]glycerol MIDA. We conclude that in VLBW infants receiving TPN, normoglycemia was maintained during reduced glucose infusion by glucose production primarily derived from gluconeogenesis, and that glycerol was the principal gluconeogenic substrate.  (+info)

Acn9 is a novel protein of gluconeogenesis that is located in the mitochondrial intermembrane space. (7/1508)

Previous studies have indicated that the Acn9 protein is involved in gluconeogenesis. Yeast mutants defective in the ACN9 gene display phenotypes identical with mutants defective in metabolic enzymes required for carbon assimilation. These phenotypes include the inability to utilize acetate as a carbon and energy source, elevated levels of enzymes of the glyoxylate cycle, gluconeogenesis and acetyl-CoA mobilization, and a deficiency in de novo synthesis of glucose from ethanol. The ACN9 gene was isolated by functional complementation of the acetate growth defect of an acn9 mutant. The open reading frame corresponds to YDR511w, and encodes a protein of unknown function. Homologs have been identified in human, mouse, and nematode databases. Two mutant alleles were sequenced. The mutations altered amino acid residues that are conserved among members of the new gene family. ACN9 gene expression was slightly repressed by glucose, and the level of the transcript was approximately 100-fold lower than that of glyoxylate or tricarboxylic acid cycle enzymes. A functional epitope-tagged form of Acn9 was expressed to study expression and the subcellular localization of the protein. The tagged protein was localized to the mitochondrial intermembrane space.  (+info)

Effects of a high-fat diet and voluntary wheel running on gluconeogenesis and lipolysis in rats. (8/1508)

The purpose of the present study was to determine the effects of diet composition and exercise on glycerol and glucose appearance rate (Ra) and on nonglycerol gluconeogenesis (Gneo) in vivo. Male Wistar rats were fed a high-starch diet (St, 68% of energy as cornstarch, 12% corn oil) for a 2-wk baseline period and then were randomly assigned to one of four experimental groups: St (n = 7), high-fat (HF; 35% cornstarch, 45% corn oil; n = 8), St with free access to exercise wheels (StEx; n = 7), and HF with free access to exercise wheels (HFEx; n = 7). After 8 wk, glucose Ra when using [3-3H]glucose, glycerol Ra when using [2H5]glycerol (estimate of whole body lipolysis), and [3-13C]alanine incorporation into glucose (estimate of alanine Gneo) were determined. Body weight and fat pad mass were significantly (P < 0.05) decreased in exercise vs. sedentary animals only. The average amount of exercise was not significantly different between StEx (3,212 +/- 659 m/day) and HFEx (3,581 +/- 765 m/day). The ratio of glucose to alanine enrichment and absolute glycerol Ra (micromol/min) were higher (P < 0.05) in HF and HFEx compared with St and StEx rats. In separate experiments, the ratio of 3H in C-2 to C-6 of glucose from 3H2O (estimate of Gneo from pyruvate) was also higher (P < 0.05) in HF (n = 5) and HFEx (n = 5), compared with St (n = 5) and StEx (n = 5) rats. Voluntary wheel running did not significantly increase estimated alanine or pyruvate Gneo or absolute glycerol Ra. Voluntary wheel running increased (P < 0.05) glycerol Ra when normalized to fat pad mass. These data suggest that a high-fat diet can increase in vivo Gneo from precursors that pass through pyruvate. They also suggest that changes in the absolute rate of glycerol Ra may contribute to the high-fat diet-induced increase in Gneo.  (+info)

  • A gene expression microarray screen followed by constraint-based modeling (CBM) predicting metabolic changes imposed by the transcriptomic changes suggested a role for p53 in enhancing gluconeogenesis ( de novo synthesis of glucose). (biomedcentral.com)
  • However, on a ketogenic diet, because protein and calories are not scarce, any excess dietary protein will be readily utilized to bolster gluconeogenesis. (drhoffman.com)
  • Any excess protein will shift metabolism back to glycolysis and away from lipolysis/ketosis via gluconeogenesis. (drhoffman.com)
  • Once gluconeogenesis is established, our bodies can readily make glucose from the protein we eat. (blogspot.com)
  • Covers all of the steps of gluconeogenesis clearly whilst giving students an insight into protein structure. (origamiorganelles.com)
  • What is the recommended low carb diet daily protein amount to avoid gluconeogenesis? (allnaturalideas.com)
  • Will eating lots of protein if you're low carb lead to gluconeogenesis? (allnaturalideas.com)
  • Based on what is known of these proteins from prior research, they are involved in a variety of cellular processes including protein turnover, detoxification, purine biosynthesis, gluconeogenesis, lipid metabolism and mobility, ketone body formation, cell structure, and redox balance. (mcponline.org)
  • Generally, consumption of gluconeogenic substrates in food does not result in increased gluconeogenesis. (wikipedia.org)
  • In asexual spores, mRNAs for gluconeogenic, glyoxylate cycle, and β-oxidation enzymes as well as peroxisomes are present, indicating that gluconeogenesis may be significant for spore survival and germination via the use of stored lipids. (asmscience.org)
  • It is known that odd-chain fatty acids can be oxidized to yield propionyl-CoA, a precursor for succinyl-CoA, which can be converted to pyruvate and enter into gluconeogenesis. (wikipedia.org)
  • The ATP required for gluconeogenesis is supplied by the oxidation of long-chain fatty acids. (guwsmedical.info)
  • During both fasting and recovery from prolonged exercise, the substantial energy cost of gluconeogenesis is met primarily by concurrent b-oxidation of fatty acids to acetyl-CoA in the liver. (reachingfordreams.com)
  • The location of the enzyme that links these two parts of gluconeogenesis by converting oxaloacetate to PEP, PEP carboxykinase, is variable by species: it can be found entirely within the mitochondria, entirely within the cytosol, or dispersed evenly between the two, as it is in humans. (wikibooks.org)
  • Therefore species that lack intra-mitochondrial PEP, oxaloacetate must be converted into malate or asparate, exported from the mitochondrion, and converted back into oxaloacetate in order to allow gluconeogenesis to continue. (wikibooks.org)
  • Gluconeogenesis is the reverse of glycolysis, with an extra step, which means it is a process that requires energy to be put into the reaction in order for it to occur. (study.com)
  • A maximal rate of net gluconeogenesis can therefore be estimated from the uptake of all possible substrates by the liver (let us consider only this organ for the sake of simplicity) ( 1 , 20 , 28 ). (physiology.org)
  • Gluconeogenesis is a biochemical process through which the organs or cells can synthesize glucose from non-carbohydrate carbon substrates and is important for blood glucose homeostasis. (tamu.edu)
  • In addition, the HFru and HSu groups showed increased lipogenesis, gluconeogenesis, reduced beta-oxidation and antioxidant imbalance compared with the SC animals. (rsc.org)
  • An autosomal recessive metabolic disorder caused by absent or decreased pyruvate carboxylase activity, the enzyme that regulates gluconeogenesis, lipogenesis, and neurotransmitter synthesis. (icd10data.com)
  • Studies found that Pck-1 gene is often down-regulated by anti-diabetic drugs, as its enzyme is responsible for catalyzing the rate-limiting step of gluconeogenesis. (ahajournals.org)
  • I am using the term gluconeogenesis in this lecture to denote any new formation of carbohydrate from non-carbohydrates. (royalsocietypublishing.org)
  • MAPK phosphatase 3 can promote gluconeogenesis by dephosphorylating FoxO1 in mouse liver and PP2A was reported to be a phosphatase which can dephosphorylate FoxO1/3a in vitro and in cells. (tamu.edu)
  • Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. (nih.gov)
  • Gluconeogenesis helps in clearing certain metabolites produced in the tissues, which accumulates in the blod, e.g. (ittopic4.xyz)