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Biomedical subjects

D M Bier

Publications and source records attributed to D M Bier.

At least 127 records · Page 7Linked to original sources
PubMed1983

Identification of type I diabetic patients at increased risk for hypoglycemia during intensive therapy.

During intravenous insulin infusions (40 mU per kilogram of body weight per hour for up to 100 minutes), 9 of 22 patients with insulin-requiring diabetes mellitus had neurologic signs or symptoms of hypoglycemia, plasma glucose concentrations that were below 35 mg per deciliter (1.9 mmol per liter) and continued to decline, or both. This inadequate glucose counterregulation resulted from the combined effect of deficient glucagon and epinephrine responses. In 8 of the 9 patients with inadequate counterregulation severe hypoglycemia developed during subsequent intensive therapy, whereas such episodes occurred in only 1 of 13 patients with adequate counterregulation. Thus, an intravenous insulin-infusion test can prospectively identify patients who are at increased risk for recurrent severe hypoglycemia during intensive therapy for diabetes.

Adolescent↗
PubMed1983

Direct alpha-adrenergic stimulation of hepatic glucose production in human subjects.

Six normal humans each underwent infusions of 1) saline; 2) propranolol; 3) somatostatin; 4) somatostatin with propranolol; and 5) somatostatin with propranolol plus phentolamine on separate occasions. Propranolol alone had no effect on glucose production or plasma glucose. Somatostatin alone produced the expected initial decrease followed by an increase in both hepatic glucose production and plasma glucose. beta-Adrenergic blockade with propranolol displaced the glucose production (MANOVA, P = 0.0220) and plasma glucose (MANOVA, P = 0.0057) somatostatin response curves to higher levels, whereas alpha-adrenergic blockade with phentolamine combined with beta-adrenergic blockade displaced the glucose production (MANOVA, P = 0.0281) and plasma glucose (MANOVA, P = 0.0134) somatostatin response curves to lower levels. Because plasma insulin, C-peptide, and glucagon were suppressed comparably under all three conditions and plasma glucose concentrations were comparable initially, this represents direct alpha-adrenergic stimulation of hepatic glucose production in postabsorptive humans demonstrable when the primary glucoregulatory hormones are withdrawn and beta-adrenergic mechanisms are blocked. It is best attributed to sympathetic neural norepinephrine release.

Adult↗
PubMed1983

Hypoglycemia, hepatic dysfunction, muscle weakness, cardiomyopathy, free carnitine deficiency and long-chain acylcarnitine excess responsive to medium chain triglyceride diet.

Fraternal twins who had fasting hypoglycemia, hypoketonemia, muscle weakness, and hepatic dysfunction are reported. The hepatic dysfunction occurred only during periods of caloric deprivation. The surviving patient developed a cardiomyopathy. In this sibling, muscle weakness and cardiomyopathy were markedly improved by a diet high in medium chain triglycerides. There was a marked deficiency of muscle total carnitine and a mild deficiency of hepatic total carnitine. Unlike patients with systemic carnitine deficiency, serum and muscle long-chain acylcarnitine were elevated and renal reabsorption of carnitine was normal. It was postulated that the defect in long-chain fatty acid oxidation in this disorder is caused by an abnormality in the mitochondrial acylcarnitine transport. Detailed studies of the cause of the hypoglycemia revealed that insulin, growth hormone, cortisol, and glucagon secretion were appropriate and that it is unlikely that there was a major deficiency of a glycolytic or gluconeogenic enzyme. Glucose production and alanine conversion to glucose were in the low normal range when compared to normal children in the postabsorptive state. The hypoglycemia in our patients was probably due to a modest increase in glucose consumption, secondary to the decreased oxidation of fatty acids and ketones, alternate fuels which spare glucose utilization, plus a modest decrease in hepatic glucose production secondary to decreased available hepatic energy substrates.

Cardiomyopathies↗
PubMed1983

Exercise and blood pressure: nutritional considerations.

Exercise dramatically alters metabolic fuel balance and thus affects nutrient requirements. Because amino acids only serve a minor fuel role in exercise, the effect of work on protein requirements has received little recent attention. However, current research into the regulatory roles of amino acids (notably leucine) on muscle metabolism has led to renewed investigation of the substrate homeostatic functions of amino acids during exercise. These interests, coupled with reassessment of the limitations of recommendations for dietary amino acid intake obtained by the balance method and introduction of new tracer kinetic approaches for estimating nutrient requirements, have raised the possibility that exercise of high intensity or long duration may alter dietary amino acid needs to an extent not previously appreciated.

Amino Acids↗
PubMed1982

The stimulus-secretion coupling of amino acid-induced insulin release. Metabolic response of pancreatic islets of L-glutamine and L-leucine.

L-Glutamine markedly enhances insulin release evoked by L-leucine in rat pancreatic islets. The metabolic situation found in the islets exposed to both L-glutamine and L-leucine was investigated. L-Leucine slightly decreased the rate of L-glutamine deamidation, inhibited the conversion of glutamate to 2-ketoglutarate by transamination, increased the oxidative deamination of L-glutamate, stimulated the recirculation of 2-ketoglutarate to glutamate and inhibited the further oxidative metabolism of 2-ketoglutarate. L-Glutamine slightly decreased the rate of L-leucine conversion to 2-ketoisocaproate, but inhibited more severely the conversion of 2-ketoisocaproate to acetoacetate and CO2. Several of these findings appeared attributable to activation of glutamate dehydrogenase by L-leucine. When allowance was made for the influence of exogenous amino acids on the oxidation of endogenous fatty acids, a close parallelism was found between the rate of generation of reducing equivalents or O2 uptake and the insulin secretory response to L-leucine and/or L-glutamine. These findings reinforce the view that the process of nutrient-stimulated insulin release coincides with and may be attributable to an increase in catabolic fluxes in the islet cells.

Animals↗
PubMed1982

Hepatic ultrastructure in leprechaunism. Hepatic ultrastructural evidence suggesting a syndrome with defective hepatic glucose release.

Leprechaunism is a congenital syndrome with characteristic habitus and facies, with fasting hypoglycemia and hyperinsulinism. In response to a glucose challenge there is prolonged severe hyperglycemia with an increased hyperinsulinemia. Our studies on such a patient showed a normal response of the serum glucose to glucagon stimulation in the fed state but no response in the postabsorptive state. Ultrastructural studies on the hepatocytes demonstrated that a lack of hepatic glycogen was not responsible for the biochemical features, since there was abundant normal beta-glycogen in both the fed and fasting state, the granules being smaller in the fasted state. We speculate that carbohydrate intolerance in leprechaunism may be due to a relative insulin resistance of cell receptors in the fed state. Reactive hyperinsulinemia persisting into the postabsorptive phase appears to antagonize the usual glycogenolytic response to glucagon during fasting, resulting in hypoglycemia despite the presence of large hepatic glycogen stores.

Child, Preschool↗
PubMed1982

Glucose and insulin effects on the novo amino acid synthesis in young men: studies with stable isotope labeled alanine, glycine, leucine, and lysine.

We have explored interrelationships between te dynamic aspects of whole body glucose and alanine and glycine metabolism in adult humans. Using a primed, continuous intravenous infusion of [1-13C] leucine or lysine given simultaneously with [2H3] or [15N]alanine or [15N]glycine, respectively, whole body alanine and glycine fluxes and their rates of de novo synthesis were determined in three experiments with healthy young men. Subjects were studied in the post-absorptive state and during a 150 min period of an intravenous infusion with unlabeled glucose, at a rate of 4 mg.kg-1 min-1. In one experiment, insulin was given together with the glucose infusion to maintain normoglycemia. In the other two studies, subjects received glucose alone. For the post-absorptive state, alanine flux (mean +/- SEM) was 381 +/- 26 and 317 +/- 18 mumole.kg-1 hr-1 in two separate experiments and glycine flux was 240 +/- 22 mumole.kg-1 hr-1. De novo synthesis of alanine and glycine accounted for 75%-81% and 81% of flux, respectively. Infusion with glucose alone raised plasma glucose to a mean level of 152 mg/dl and increased alanine flux, due to a rise in alanine synthesis of 98 mumole.kg-1 hr-1 (p less than 0.01). Glycine flux and synthesis rate were unaffected by the glucose infusion. When insulin was given with glucose to maintain normoglycemia, the rate of alanine synthesis was unchanged. Because glucose uptake rate, measured with [6,6-2H2] glucose was the same whether glucose was infused along or with exogenous insulin, these results support the view that the circulating plasma glucose level itself may affect alanine synthesis and that the hyperglycemic state is an important factor in regulating interorgan nitrogen transfer, via alanine, in various pathophysiologic states.

Adult↗
PubMed1982

The conversion of phenylalanine to tyrosine in man. Direct measurement by continuous intravenous tracer infusions of L-[ring-2H5]phenylalanine and L-[1-13C] tyrosine in the postabsorptive state.

Steady state phenylalanine and tyrosine turnover and the rate of conversion of phenylalanine of tyrosine in vivo were determined in 6 healthy postabsorptive adult volunteers. Continuous infusions of tracer amounts of L-[ring-2H5]phenylalanine were determined intravenously for 13-14 hr. After 9-10 hr, a priming dose followed by a continuous infusion of L-[1-13C]tyrosine was added and maintained, along with the [2H5]phenylalanine infusion, for 4 hr. Venous plasma samples were obtained before the initiation of each infusion and every 30 min during the course of the combined [2H5]phenylalanine and [13C]tyrosine infusion for determination of isotopic enrichments of [2H5]phenylalanine, [13C]tyrosine, and [2H4]tyrosine by gas chromatograph-mass spectrometric analysis of the N-trifluoroacetyl-, methyl ester derivatives of the amino acids. Calculated from the observed enrichments, free phenylalanine and tyrosine turnover rates were 36.1 +/- 5.1 mumole . kg-1 . h-1 and 39.8 +/- 3.5 mumole . kg-1 . h-1, respectively. Phenylalanine was converted to tyrosine at the rate of 5.83 +/- 0.59 mumole . kg-1 . h-1, accounting for approximately 16% of either the phenylalanine or the tyrosine flux. The results indicate that the normal basal steady state phenylalanine hydroxylase activity in vivo in man is lower than that obtained from phenylalanine loading studies. This supports the existence of some type of substance activation of the enzyme as reflected in the previously reported exponential relationship between phenylalanine concentration and phenylalanine hydroxylase activity in vitro. The use of continuous simultaneous infusions of tracer amounts of stable isotope-labeled phenylalanine and tyrosine provides a direct means for studying physiological regulation of phenylalanine hydroxylase activity in vivo.

Absorption↗
PubMed1982

Relationship of plasma leucine and alpha-ketoisocaproate during a L-[1-13C]leucine infusion in man: a method for measuring human intracellular leucine tracer enrichment.

The keto analog of leucine, alpha-ketoisocaproate (KIC), is formed intracellularly from leucine and is released, in part, into the systemic circulation. Therefore. KIC can be used to estimate intracellular leucine tracer enrichment in man during labeled-leucine tracer experiments without requiring tissue biopsy samples. This approach was studied in young, healthy, male adults maintained on different dietary protein intakes from generous (1.5 g kg-1d-1) to deficient (0.0 g kg-1d-1) for 5-7 day periods. At the end of each dietary period, the volunteers were given a primed, continuous infusion of L-[1-13C]leucine either after an overnight fast (postabsorptive state) or while being fed hourly aliquots of the same diet. The plasma concentrations of all 3 branched-chain amino and keto acid pairs were measured from early morning blood samples taken from 4 subjects at 4 different levels of protein intake. Leucine concentration showed a weak correlation, and valine concentration showed a strong correlation with protein intake; isoleucine and the 3 keto acids did not. However, each branched-chain amino acid concentration was strongly correlated with its corresponding keto acid concentration. In plasma samples obtained during the L-[1-13C]leucine infusions, the ratio of [1-13C]KIC to [1-13C]leucine enrichment ratio remained relatively constant (77 +/- 1% over the wide range of dietary protein intakes and for both the fed and postabsorptive states. For the tissues from which the plasma KIC originates, the rate of plasma leucine into cells will account for approximately 77% of the intracellular leucine flux with the remaining 23% coming primarily from leucine release via protein breakdown. The constant nature of the plasma KIC to leucine 13C enrichment ratio implies that relative changes in leucine kinetics will appear the same under many dietary circumstances regardless of whether plasma leucine or KIC enrichments are used for the calculations.

Adult↗
PubMed1982

Galactose intolerance in individuals with double heterozygosity for Duarte variant and galactosemia.

The most frequent cause for an abnormal result during screening of newborn infants for galactosemia is double heterozygosity for Duarte variant and galactosemia, in which galactose-1-phosphate uridyl transferase activity is reduced to approximately 17% of normal. Thirty-nine oral galactose tolerance tests were performed in 27 infants and children with this condition. In comparison to age-matched controls, all children with this genetic variant reached much higher levels of blood galactose and galactose-1-phosphate following oral galactose challenge. The integrated plasma galactose response increased with the age of the child, whereas integrated erythrocyte galactose-1-phosphate responses were elevated to the same degree at all ages. Although all children appeared clinically normal, the marked abnormalities in the ability to dispose of ingested galactose raise questions concerning appropriate dietary recommendations for such children.

Blood Glucose↗
PubMed1982

Lipid transport in the human newborn. Palmitate and glycerol turnover and the contribution of glycerol to neonatal hepatic glucose output.

Free fatty acid (FFA) transport was measured in 11 and glycerol turnover in 5 newborns with continuous tracer infusion of [1-(13)C]palmitate or [2-(13)C]glycerol, respectively. In addition, simultaneous determination of glucose production in the latter group with [6,6-(2)H(2)]glucose tracer and measurement of the appearance rate of [(13)C]glucose derived from [(13)C]glycerol allowed calculation of gluconeogenesis from glycerol.The average FFA inflow rate was 11.5+/-1.7 mumol kg(-1)min(-1), 2.5-4.5 h after the last feeding, and 16.7+/-2.8 mumol kg(-1)min(-1), 5-12 h after the last meal. These rates are comparable to those found in adults only after 8-16 h and approximately 72 h of fasting, respectively. FFA inflow in the newborn was directly correlated with time of fasting, plasma FFA level, and plasma glycerol level. Palmitate clearance and fractional removal were inversely related to palmitate level. Glycerol flux averaged 4.4+/-0.5 mumol kg(-1)min(-1), a value three- to fourfold that of the postabsorptive adult. Approximately 75% of transported glycerol was converted to glucose and represented 5.0+/-0.6% of hepatic glucose production. Furthermore, there was a direct relationship between glycerol turnover and the fraction of glucose coming from glycerol. Despite the absolutely elevated neonatal FFA and glycerol transport rates, these were quantitatively similar to values found in adults with comparable elevated substrate levels. Furthermore, other similarities with the adult in the relationships between inflow transport and substrate values, and between transport and fractional removal suggest that the regulatory aspects of lipid transport in man are already well developed by the first day of life.

Blood Glucose↗
PubMed1982

Quantitative aspects of glucose production and metabolism in healthy elderly subjects.

The metabolic basis for the reduced glucose tolerance that occurs during aging in humans has been explored with the aid of a primed constant intravenous infusion method of labeled glucose (6-3H; 6,6,2H- and U-13C-glucose). Healthy young adult men and women (24 +/- 3 yr) and elderly men and women (75 +/- 4 yr) participated in a series of studies designed to quantify rates of plasma glucose appearance, oxidation, and recycling while subjects were in the postabsorptive (basal) state and to determine rates of hepatic glucose production and glucose disappearance in response to intravenous glucose at approximately 1 and 2 mg x kg-1min-1 and also 4 mg x kg-1min-1 without or with a simultaneous infusion of insulin to maintain normoglycemia. Basal rates of glucose production were 2.41 +/- 0.06 and 2.18 /+/- 0.05 mg x kg-1min-1 in the young adults and elderly, respectively (P less than 0.05). Recycling of glucose carbon and glucose oxidation rates did not differ significantly between the two age groups. Infusion of unlabeled glucose reduced hepatic glucose production to the same extent in the two groups, indicating that the mechanisms responsible for altered hepatic glucose production with intravenous glucose administration remain intact during human aging. Plasma insulin changes were similar in young adult and elderly subjects receiving 4 mg x kg-1min-1 unlabeled glucose except that the higher plasma glucose levels in the elderly were associated with higher insulin levels. For elderly subjects, the amount of exogenous insulin required to maintain normoglycemia at the 4 mg x kg-1min-1 glucose infusion rate was about twice that necessary in young adults.

Adult↗
PubMed1982

Whole body leucine metabolism in adolescents with Crohn's disease and growth failure during nutritional supplementation.

The adaptive response of whole body leucine metabolism to nutritional supplementation was determined in 6 adolescents with Crohn's disease and growth failure. Five healthy adolescents served as controls for body composition studies. In the first study period, all subjects received a constant diet comparable to usual intakes. In the second period, the patients were given overnight intragastric supplemental feedings that increased dietary protein and energy intakes approximately 40% (to 3.2 g/kg . day and 96 kcal/kg . day, respectively). During each dietary period, O2 consumption, nitrogen balance, whole body potassium (40K), and urinary creatinine measurements were obtained on all adolescents, and the patients received a primed, constant, intravenous infusion of [13C]leucine for 4 h in the fed state. Plasma leucine and expired carbon dioxide 13C-enrichments were determined by mass spectrometric techniques. In the first study, O2 consumption and nitrogen balances were similar between groups; in patients, 40K and urinary creatinine were reduced by 30% and 36%, respectively. With nutritional supplementation, nitrogen balance increased fourfold; O2 consumption and 40K increased by 32% and 10%, respectively. Similarly, whole body leucine flux increased from 166.9 +/- 5.9 to 201.3 +/- 11.2 mumol/kg . h (p less than 0.05) due to a 66% increase in leucine incorporation into body protein (p less than 0.01) and a 41% decrease in leucine oxidation (p less than 0.05). Thus, these studies demonstrate that the mechanisms responsible for lean body mass accretion during nutritional supplementation in adolescents with Crohn's disease and growth failure are increased rates of amino acid incorporation into body protein (via protein synthesis) and decreased rates of amino acid oxidation.

Adolescent↗
PubMed1982

Stable isotope dilution method for measurement of palmitate content and labeled palmitate tracer enrichment in microliter plasma samples.

In studies where [1-13C]palmitic acid is employed as isotopic tracer in vivo, we have described a selected ion monitoring gas-liquid chromatography-mass spectrometry micro-method which allows plasma tracer enrichment as well as plasma palmitate content to be determined in the same 100-microliter sample through the use of [5,5,6,6-2H4]palmitic acid as assay internal standard. For standard solutions in the range equivalent to plasma palmitic acid concentrations of 10--2500 microM, assay precision was +/- 5%. For plasma samples in the physiologic range (approximately 30--200 microM palmitate) assay precision averaged better than +/- 2%. The use of the method is illustrated by measuring palmitate turnover in a 12-hr-old human infant.

Carbon Isotopes↗
PubMed1982

Stable isotope tracer methods for in vivo investigations.

During the last two decades, in parallel with the growth of modern electronics, several new techniques have been developed for measuring stable isotopic enrichments in biochemistry and medicine. The development and potential of these techniques are discussed. Of these methods, mass spectrometry has been developed and refined the fullest to quantitate stable isotope tracers in very minute samples and for very large dilutions of tracer. No single mass spectrometric technique can measure this entire range, and different techniques are used for different applications. Examples of the different methods are presented for determining whole-body amino acid and protein dynamics in humans with stable isotopically labeled amino acid tracers.

Activation Analysis↗
PubMed1982

Endocrine-metabolic relationships in patients with leprechaunism.

Leprechaunism is a rare, heritable syndrome, associated with multiple dysmorphic and pathologic features, suggestive of an endocrine dysfunction. Few endocrine and metabolic studies have been obtained because of the rarity of the syndrome, and the small size and early demise of these infants. The authors present here the clinical, anatomic, and endocrine-metabolic studies of three patients, with a view toward careful delineation of the syndrome and further characterization of the metabolic defect.The most striking and consistent metabolic derangements present in all of these patients were fasting hypoglycemia (less than 20 mg/dL), postprandial hyperglycemia (more than 250 mg/dL), marked hyperinsulinemia (more than 2000 μU/mL), and severe insulin resistance (less than a 20 percent decrease in blood sugar with 0.3 to 1.0 U/kg of regular insulin IV). Hyperinsulinemia was observed in response to oral feedings and glucose infusion, and after tolbutamide. Insulin secretion was less marked with amino acid infusions. Normal increments in blood glucose occurred following alanine, galactose, and glycerol. Glucagon caused a rise in glucose 4 hours after a meal, but no response was seen after a 12-hour fast. Pituitary, gonadal, and adrenal hormone levels were normal, and there was a normal response pattern to GnRH and TRH. Hyperinsulinemia would appear to be the biochemical hallmark of this disease. Our previous studies were suggestive of a postreceptor defect in insulin action. The present endocrine-metabolic studies are compatible with this hypothesis. Interaction of supraphysiologic concentrations of plasma insulin with growth factor receptors, this may provide a partial explanation for some of the dysmorphic features seen in the disorder.

Adult↗