Bjørn Quistorff

Bio: Bjørn Quistorff is an academic researcher from University of Copenhagen. The author has contributed to research in topics: Skeletal muscle & Carbohydrate metabolism. The author has an hindex of 38, co-authored 146 publications receiving 5080 citations. Previous affiliations of Bjørn Quistorff include Hvidovre Hospital.

Blood Lactate is an Important Energy Source for the Human Brain

Abstract: ��������� � �� ���������� Lactate is a potential energy source for the brain. The aim of this study was to establish whether systemic lactate is a brain energy source. We measured in vivo cerebral lactate kinetics and oxidation rates in 6 healthy individuals at rest with and without 90 mins of intravenous lactate infusion (36 lmol per kg bw per min), and during 30 mins of cycling exercise at 75% of maximal oxygen uptake while the lactate infusion continued to establish arterial lactate concentrations of 0.89±0.08, 3.9±0.3, and 6.9±1.3 mmol/L, respectively. At rest, cerebral lactate utilization changed from a net lactate release of 0.06±0.01 to an uptake of 0.16±0.07 mmol/min during lactate infusion, with a concomitant decrease in the net glucose uptake. During exercise, the net cerebral lactate uptake was further increased to 0.28±0.16 mmol/min. Most 13 C-label from cerebral [1- 13 C]lactate uptake was released as 13 CO2 with 100%±24%, 86%±15%, and 87%±30% at rest with and without lactate infusion and during exercise, respectively. The contribution of systemic lactate to cerebral energy expenditure was 8%±2%, 19%±4%, and 27%±4% for the respective conditions. In conclusion, systemic lactate is taken up and oxidized by the human brain and is an important substrate for the brain both under basal and hyperlactatemic conditions.

Impact of short-term high-fat feeding on glucose and insulin metabolism in young healthy men

Abstract: A high-fat, high-calorie diet is associated with obesity and type 2 diabetes. However, the relative contribution of metabolic defects to the development of hyperglycaemia and type 2 diabetes is controversial. Accumulation of excess fat in muscle and adipose tissue in insulin resistance and type 2 diabetes may be linked with defective mitochondrial oxidative phosphorylation. The aim of the current study was to investigate acute effects of short-term fat overfeeding on glucose and insulin metabolism in young men. We studied the effects of 5 days’ high-fat (60% energy) overfeeding (+50%) versus a control diet on hepatic and peripheral insulin action by a hyperinsulinaemic euglycaemic clamp, muscle mitochondrial function by 31P magnetic resonance spectroscopy, and gene expression by qrt-PCR and microarray in 26 young men. Hepatic glucose production and fasting glucose levels increased significantly in response to overfeeding. However, peripheral insulin action, muscle mitochondrial function, and general and specific oxidative phosphorylation gene expression were unaffected by high-fat feeding. Insulin secretion increased appropriately to compensate for hepatic, and not for peripheral, insulin resistance. High-fat feeding increased fasting levels of plasma adiponectin, leptin and gastric inhibitory peptide (GIP). High-fat overfeeding increases fasting glucose levels due to increased hepatic glucose production. The increased insulin secretion may compensate for hepatic insulin resistance possibly mediated by elevated GIP secretion. Increased insulin secretion precedes the development of peripheral insulin resistance, mitochondrial dysfunction and obesity in response to overfeeding, suggesting a role for insulin per se as well GIP, in the development of peripheral insulin resistance and obesity.

Lactate, glucose and O2 uptake in human brain during recovery from maximal exercise.

Abstract: Controversy exists as to whether the metabolic activity of the brain as a whole increases during physical exercise. For example, there appears to be no change in brain O2 uptake during cycling (Zobl et al. 1965; Madsen et al. 1993), whereas during vigorous exercise on the treadmill an increase in brain O2 uptake and a tendency for glucose uptake to increase has been reported (Scheinberg et al. 1954). In the case of mental stress, there is no appreciable change in brain O2 uptake but there is an increase in cerebral glucose uptake (Madsen et al. 1995a). Thus, the rate of glucose uptake is enhanced compared to that of O2. Interestingly, the ‘uncoupling’ between the O2 and glucose uptake rates is sustained even after the cessation of brain activation (Madsen et al. 1995a,b) and may be associated with a decrease in the glycogen level in the brain (Madsen et al. 1995a). During maximal exercise, blood lactate increases to as much as 30 mmol l−1 (Nielsen, 1999) and the brain is known to take up lactate (Ahlborg & Wahren, 1972). Lactate transport across mammalian plasma membranes is mainly carrier mediated (Poole et al. 1993) and a monocarboxylate transporter is found in rat brain endothelium cells (Gerhart et al. 1997). Brain tissue, including neurons (Dringen et al. 1993) and astrocytes (Tildon et al. 1993), possesses the capacity to take up and utilise lactate as an energy source. In fact, lactate rather than glucose may be the primary energy source during neuronal activation (Larrabee, 1996) when lactate is supplied by the glial cells to the neurons (Poitry-Yamate et al. 1995). A positive arterial-jugular venous concentration difference (a–v difference) for lactate has been demonstrated in the dog (Nemoto et al. 1974; Avogaro et al. 1990) and in humans during cardiopulmonary resuscitation (Rivers et al. 1991). Taken together, these reports led us to hypothesise that the metabolic rate for the brain is increased during exercise and also in the recovery phase when lactate, in addition to glucose and O2, is taken into consideration as a metabolic substrate. Therefore, we investigated the a–v differences for glucose, lactate and O2 at rest, during exercise and in the immediate recovery period. Since arterial CO2 tension increases during moderate exercise and decreases during maximal exercise (Jorgensen et al. 1992), we applied an index of the metabolic rate of the brain that would be independent of flow, i.e. we calculated the O2/carbohydrate uptake ratio. In a separate experiment in the rat, we investigated whether an increase in blood lactate per se would influence brain uptake of lactate.

Lactate fuels the human brain during exercise

Abstract: The human brain releases a small amount of lactate at rest, and even an increase in arterial blood lactate during anesthesia does not provoke a net cerebral lactate uptake. However, during cerebral activation associated with exercise involving a marked increase in plasma lactate, the brain takes up lactate in proportion to the arterial concentration. Cerebral lactate uptake, together with glucose uptake, is larger than the uptake accounted for by the concomitant O2 uptake, as reflected by the decrease in cerebral metabolic ratio (CMR) [the cerebral molar uptake ratio O2/(glucose+½ lactate)] from a resting value of 6 to <2. The CMR also decreases when plasma lactate is not increased, as during prolonged exercise, cerebral activation associated with mental activity, or exposure to a stressful situation. The CMR decrease is prevented with combined β1- and β2-adrenergic receptor blockade but not with β1-adrenergic blockade alone. Also, CMR decreases in response to epinephrine, suggesting that a β2-adrenergic ...

Heat production in human skeletal muscle at the onset of intense dynamic exercise

Abstract: 1. We hypothesised that heat production of human skeletal muscle at a given high power output would gradually increase as heat liberation per mole of ATP produced rises when energy is derived from oxidation compared to phosphocreatine (PCr) breakdown and glycogenolysis. 2. Five young volunteers performed 180 s of intense dynamic knee-extensor exercise ( approximately 80 W) while estimates of muscle heat production, power output, oxygen uptake, lactate release, lactate accumulation and ATP and PCr hydrolysis were made. Heat production was determined continuously by (i) measuring heat storage in the contracting muscles, (ii) measuring heat removal to the body core by the circulation, and (iii) estimating heat transfer to the skin by convection and conductance as well as to the body core by lymph drainage. 3. The rate of heat storage in knee-extensor muscles was highest during the first 45 s of exercise (70-80 J s-1) and declined gradually to 14 +/- 10 J s-1 at 180 s. 4. The rate of heat removal by blood was negligible during the first 10 s of exercise, rising gradually to 112 +/- 14 J s-1 at 180 s. The estimated rate of heat release to skin and heat removal via lymph flow was < 2 J s-1 during the first 5 s and increased progressively to 24 +/- 1 J s-1 at 180 s. The rate of heat production increased significantly throughout exercise, being 107 % higher at 180 s compared to the initial 5 s, with half of the increase occurring during the first 38 s, while power output remained essentially constant. 5. The contribution of muscle oxygen uptake and net lactate release to total energy turnover increased curvilinearly from 32 % and 2 %, respectively, during the first 30 s to 86 % and 8 %, respectively, during the last 30 s of exercise. The combined energy contribution from net ATP hydrolysis, net PCr hydrolysis and muscle lactate accumulation is estimated to decline from 37 % to 3 % comparing the same time intervals. 6. The magnitude and rate of elevation in heat production by human skeletal muscle during exercise in vivo could be the result of the enhanced heat liberation during ATP production when aerobic metabolism gradually becomes dominant after PCr and glycogenolysis have initially provided most of the energy.

Preparation of isolated rat liver cells.

Abstract: Publisher Summary This chapter discusses preparation of isolated rat liver cells The early mechanical and chemical methods for liver-cell preparation were relatively successful in converting liver tissue to a suspension of isolated cells The successful preparation of intact liver cells by perfusion with collagenase is technically quite difficult The major method for preparation of nonparenchymal liver cells is based on the selective sensitivity of parenchymal cells toward proteases By incubation of rat liver minces with pronase, most of the liver parenchyma is digested, while nonparenchymal cells remain intact and can be recovered from the incubate Similar results have been reported with trypsin digestion of collagenase-dispersed liver minces, but pronase appears to be more effective The most common procedure is to perfuse the liver briefly with pronase before it is minced and incubated with the enzyme Such direct pronase methods have been used by several investigators with yields of nonparenchymal liver cells reported to be in the range 2–15 × 10 6 cells/gm liver

Creatine and Creatinine Metabolism

Abstract: The goal of this review is to present a comprehensive survey of the many intriguing facets of creatine (Cr) and creatinine metabolism, encompassing the pathways and regulation of Cr biosynthesis an...

Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production

Abstract: The first suggestion that physical exercise results in free radical-mediated damage to tissues appeared in 1978, and the past three decades have resulted in a large growth of knowledge regarding exercise and oxidative stress. Although the sources of oxidant production during exercise continue to be debated, it is now well established that both resting and contracting skeletal muscles produce reactive oxygen species and reactive nitrogen species. Importantly, intense and prolonged exercise can result in oxidative damage to both proteins and lipids in the contracting myocytes. Furthermore, oxidants can modulate a number of cell signaling pathways and regulate the expression of multiple genes in eukaryotic cells. This oxidant-mediated change in gene expression involves changes at transcriptional, mRNA stability, and signal transduction levels. Furthermore, numerous products associated with oxidant-modulated genes have been identified and include antioxidant enzymes, stress proteins, DNA repair proteins, and mitochondrial electron transport proteins. Interestingly, low and physiological levels of reactive oxygen species are required for normal force production in skeletal muscle, but high levels of reactive oxygen species promote contractile dysfunction resulting in muscle weakness and fatigue. Ongoing research continues to probe the mechanisms by which oxidants influence skeletal muscle contractile properties and to explore interventions capable of protecting muscle from oxidant-mediated dysfunction.

AMPK in Health and Disease

Abstract: The function and survival of all organisms is dependent on the dynamic control of energy metabolism, when energy demand is matched to energy supply. The AMP-activated protein kinase (AMPK) αβγ hete...