— A method has been developed for the simultaneous measurement of the rates of glucose consumption in the various structural and functional components of the brain in vivo. The method can be applied to most laboratory animals in the conscious state. It is based on the use of 2-deoxy-D-[14C]glucose ([14C]DG) as a tracer for the exchange of glucose between plasma and brain and its phosphorylation by hexokinase in the tissues. [14C]DG is used because the label in its product, [14C]deoxyglucose-6-phosphate, is essentially trapped in the tissue over the time course of the measurement. A model has been designed based on the assumptions of a steady state for glucose consumption, a first order equilibration of the free [14C]DG pool in the tissue with the plasma level, and relative rates of phosphorylation of [14C]DG and glucose determined by their relative concentrations in the precursor pools and their respective kinetic constants for the hexokinase reaction. An operational equation based on this model has been derived in terms of determinable variables. A pulse of [14C]DG is administered intravenously and the arterial plasma [14C]DG and glucose concentrations monitored for a preset time between 30 and 45min. At the prescribed time, the head is removed and frozen in liquid N2-chilled Freon XII, and the brain sectioned for autoradiography. Local tissue concentrations of [14C]DG are determined by quantitative autoradiography. Local cerebral glucose consumption is calculated by the equation on the basis of these measured values.

The method has been applied to normal albino rats in the conscious state and under thiopental anesthesia. The results demonstrate that the local rates of glucose consumption in the brain fall into two distinct distributions, one for gray matter and the other for white matter. In the conscious rat the values in the gray matter vary widely from structure to structure (54-197 μmol/100 g/min) with the highest values in structures related to auditory function, e.g. medial geniculate body, superior olive, inferior colliculus, and auditory cortex. The values in white matter are more uniform (i.e. 33–40 μmo1/100 g/min) at levels approximately one-fourth to one-half those of gray matter. Heterogeneous rates of glucose consumption are frequently seen within specific structures, often revealing a pattern of cytoarchitecture. Thiopental anesthesia markedly depresses the rates of glucose utilization throughout the brain, particularly in gray matter, and metabolic rate throughout gray matter becomes more uniform at a lower level.

The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat.

Metformin, Independent of AMPK, Inhibits mTORC1 in a Rag GTPase-Dependent Manner

Localization of the primary metabolic block produced by 2-deoxyglucose.

http://materiais.dbio.uevora.pt/BD/Crescimento/Mitohormesis.pdf

How increased oxidative stress promotes longevity and metabolic health: The concept of mitochondrial hormesis (mitohormesis)

Publisher Summary It is now recognized that a number of factors can influence the uptake of glucose by muscle. Some are of physiological importance and these include hormones, notably insulin, growth hormone, corticosteroids, and adrenaline and possibly thyroxine and glucagon, and nonhormonal factors such as the availability of oxygen, the contractile activity of the tissue, the concentration of glucose in extracellular water, arid the availability for respiration of other substrates, such as ketone bodies and fatty acids. Other factors that influence glucose uptake arc of interest because of their hypoglycemic effects in diabetic patients and animals, notably salicylate and 2 ,4-dinitrophenol. The uptake of glucose by muscle is a complex process, which is thought to involve, in sequence, passage of the sugar from capillaries to the muscle cell membrane, transfer across the cell membrane, and metabolism within the cell by multienzyme systems with their various cofactors.

Regulation of Glucose Uptake by Muscle

SummaryThe effect of 6-deoxy-6-fluoroglucose (6-FG) on oxidation of glucose has been examined in vitro in rat epididymal adipose and rat diaphragm tissue. It was found that 6-FG at all concentrations studied was an effective inhibitor of the oxidation of glucose. However, at high 6-FG concentrations, inhibition curve of glucose oxidation approaches a maximum at approximately 75% and 50% for adipose and diaphragm tissue respectively. The inhibition curve obtained with 2-deoxyglucose, which was used for comparison purposes, appeared to asymptotically approach 100% inhibition of glucose oxidation in these tissues. These results have been interpreted to mean that 2 or more pathways previous to the hexokinase reaction appear to exist for oxidation of glucose in these tissues, and that only one of these pathways is inhibited by 6-FG.

Henry I. Nakada

Papers

Localization of the primary metabolic block produced by 2-deoxyglucose.

Influence of 6-Deoxy-6-Fluoroglucose on Glucose Utilization in Rat Epididymal Adipose Tissue and Rat Diaphragm.∗:

Glyoxylic acid oxidation by rat liver.

The effect of 2-deoxyglucose on the metabolism of glucose, fructose, and galactose by rat diaphragm

Glucosamine degradation by Escherichia coli. II. The isomeric conversion of glucosamine 6-PO4 to fructose 6-PO4 and ammonia.