Respective Control Values Research Articles

Protection by nicotinamide against streptozotocin-induced reduction in pancreatic TRH.

The concentration of thyrotrophin-releasing hormone (TRH) immunoreactivity was determined in pancreatic islets and acini in the rat. In addition, time-course changes in TRH in response to an iv injection of streptozotocin (65 mg/kg body weight) with or without nicotinamide (500 mg/kg body weight) were examined in the whole pancreas. Furthermore, pancreatic TRH was measured in diabetic rats treated with insulin for 3 weeks. The TRH concentration in rat islets was 42-fold higher than in exocrine glands, indicating that the majority of pancreatic TRH is of islet origin. The mean concentration of pancreatic TRH decreased to 60 and 65% of the respective control values at 4 and 7 h after administration of streptozotocin, respectively. AT 24 h, it fell to 10% of control values without significant changes in TRH levels in the hypothalamus and gastrointestinal tract. In contrast, no significant change in pancreatic TRH was noted in rats given combined treatment with streptozotocin and nicotinamide. The injection of streptozotocin alone resulted in severe hypoglycaemia at 7 h and hyperglycaemia at 24 h, whereas neither resulted from the combined treatment. Insulin therapy had no influence on the decreased TRH concentrations in the diabetic pancreas. These results suggest that TRH may be localized to the B cells of pancreatic islets, and that the marked reduction in TRH in diabetic pancreases is not a metabolic consequence of insulin deficiency.

Biochemical composition of muscle in normal and semistarved human subjects: relevance to anthropometric measurements

Anthropometric methods aimed at assessing muscle size in undernourished subjects assume a constant proportionality between the mass (i.e., size) and composition (specifically protein-energy content) of this tissue. This assumption was examined in three autopsy groups: controls (n = 11, sudden traumatic death), early semistarvation (n = 6), acute preterminal disease), and chronic semistarvation (n = 34, severe weight loss over time). Results of semistarved groups were expressed relative to respective control value. Early semistarvation produced no detectable change in muscle mass, protein, or total energy content (per gram wet weight), although RNA and glycogen were -50 to -70% of control value (p less than 0.05). Chronic semistarvation caused muscle atrophy (-54.2%), but not all measured constituents were reduced to the same degree. The results were H2O--52.9%, collagen--46%, noncollagen proteins--65.3%, total lipids--40%, DNA--54.1%, RNA--81.7%, glycogen--90.3%, and total energy--59.6%. Muscle per unit mass in chronic semistarvation thus reflects relatively more H2O and less protein and energy when compared to normal tissue. About 85 to 95% of muscle protein-energy loss can be detected by anthropometric measurements of muscle size; the remaining 5 to 15% depletion of protein and energy is masked by muscle compositional changes. Proper interpretation of anthropometric data requires an understanding of these unmeasured but important compositional differences in normal and semistarved muscle.

Changes in the blood chemistry of rainbow trout, Salmo gairdneri Rich, in relation to dietary protein level, and an anabolic steroid hormone, ethylestrenol

The effect of feeding isocaloric test diets containing 35, 45 and 55% protein, with and without inclusion of the anabolic steroid hormone, ethylestrenol, was studied in rainbow trout, Salmo gairdneri, in relation to blood chemistry. The control (no hormone) and experimental diets (hormone‐supplemented), were fed for a total of 60 days, after which time all groups of fish were fed an identical commercial diet with no hormone for a further 30 days (withdrawal period). After 60 days, the body weights offish fed the 35 and 45% experimental diets were significantly greater than their respective controls, and after hormone withdrawal, increased growth was still apparent in the 35% experimental group.No significant changes in serum amino acid nitrogen (AAN), protein, or glucose in relation to the dietary protein level, or inclusion of steroid, were observed after 30 days. Serum creatinine, however, increased with an increase in dietary protein, and was significantly higher in the 35% experimental group than the respective control. After 60 days, the most significant observation was the marked increase in serum glucose with an increase in dietary protein, but respective control and experimental values were not significantly different at this time. Following a 30‐day withdrawal period, serum AAN in the 55% experimental group was significantly higher than the control, whereas serum protein, creatinine, and glucose stabilized to similar concentrations in all groups. Over the 90‐day period of feeding, in both control and experimental groups, serum AAN and protein tended to increase, serum creatinine and glucose to decrease, whilst haematocrit remained constant. It is concluded that addition of ethylestrenol to trout diets has apparently little effect on serum metabolite concentrations and haematocrit, the most significant variations being related more to diet composition and duration of study.

Mineralocorticoid escape in man: role of renal prostaglandins.

The role of renal prostaglandins (PGE2 and PGF2 alpha) and kallikrein in the renal escape from excess mineralocorticoid has been evaluated in 10 normal volunteers on a high sodium diet. Escape from 9-alpha-fluorohydrocortisone (9-alpha-FF) administered for 12 days (0.6 mg daily) occurred within 4-5 days when 345 +/- 50 mmol sodium had accumulated. Indomethacin, a cyclooxygenase inhibitor, was then administered for 3 days while maintaining 9-alpha-FF. This was followed by a further cumulative gain of 105 +/- 28 mmol sodium after which escape resumed. Potassium balance remained negative throughout the study. Both PGE2 and PGF2 alpha excretion increased significantly under 9-alpha-FF from respective control values of 220 +/- 50 and 818 +/- 86 ng/24 h. to 610 +/- 317 and 1213 +/- 132 ng/24 h at the time of escape. Concomitantly urinary kallikrein increased from 1.1 +/- 0.2 to 2.5 +/- 0.3 units/24 h. Creatinine clearance increased from a mean baseline value of 111 +/- 4 to 123 +/- 4 ml/min during the same period. Indomethacin produced an inhibition of prostaglandin excretion without significant alteration of kallikrein excretion. Overall these results and particularly the transient sodium retention induced by indomethacin at the time of mineralocorticoid escape, suggest that prostaglandins may contribute to the escape phenomenon, whereas the role of kallikrein does not appear to be determinant.

Resetting of baroreflex sensitivity after induced hypotension.

The effect of sodium nitroprusside (SNP)-induced hypotension on the sensitivity of the baroreflex was studied in 11 informed patients anesthetized with morphine (M) or halothane (H). PaCO2 was controlled at 28 to 32 mmHg with a respirator. Baroreflex sensitivity was assessed with a depressor test using a small dose of SNP (4–6 μg/kg, iv) to decrease the systolic pressure (SP) rapidly by about 30 mmHg. The slope of the regression line (in ms/mmHg) relating SP and the succeeding pulse interval (PI, R-R interval) was used as an index for the sensitivity of baroreflex control of heart rate. In control measurements, SP-PI slopes were 6.4 ms/mmHg for the morphine group and 3.2 ms/mmHg for the halothane group, indicating that baroreflex sensitivity is greater during morphine than during halothane anesthesia. This difference in baroreflex sensitivity might explain the differences in dose requirements for SNP in patients anesthetized with either morphine or halothane. Following a control test, SNP was infused at a rate adjusted to maintain the mean arterial pressure between 55 and 60 mmHg. The duration of hypotension was in accordance with surgical needs. SNP infusion was then discontinued and SP was allowed to recover spontaneously. When SP recovered to its control level, PI was significantly prolonged by 18 per cent in patients anesthetized with morphine and by 13 per cent in those anesthetized with halothane over the respective control values. Immediately after the recovery of SP following the discontinuation of SNP infusion, another baroreflex sensitivity test was made; the SP-PI slopes increased markedly by 105 per cent in patients anesthetized with morphine and by 179 per cent in those with halothane over the respective control values, indicating a resetting of the baroreflex. These changes may have significant implications in hemodynamic adjustments following induced hypotension in patients during general anesthesia.

Hepatic levels of S-adenosylethionine and S-adenosylmethionine in rats and hamsters during subchronic feeding of DL-ethionine.

The levels of S-adenosylethionine (AdoEt) and of S-adenosylmethionine (AdoMet) in the livers of weanling male rats and male and female hamsters fed ethionine for 1-6 weeks were determined. Ethionine was fed at levels of 0, 0.1, and 0.3% in the diet, and the animals were sacrificed after 0, 1, 3 and 6 weeks of treatment. In both species the hepatic contents of AdoEt were dependent upon the level of ethionine in the diet. For the 6-week experimental period the hepatic levels of AdoEt average 81 microgram/g liver in male hamsters fed 0.1% ethionine in the diet and 160 microgram/g in those fed 0.3% ethionine; the corresponding AdoEt levels in female hamsters were 104 and 191 microgram/g liver, respectively. No marked shifts in hepatic AdoEt levels were seen in either male or female hamsters although a gradual rise in hepatic AdoEt from 145 to 233 microgram/g was noted in the female hamsters receiving 0.3% ethionine in the diet for 1-6 weeks. AdoEt levels in the livers of rats fed 0.3% ethionine were quite variable with values of 123, 305 and 127 microgram/g liver noted at weeks 1, 3 and 6 respectively. In rats fed the 0.1% ethionine diet the liver AdoEt levels dropped from 103 to 61 microgram/g from weeks 1 to 6, In animals fed the ethionine-free diet, the hepatic contents of AdoMet were relatively constant throughout the 6-week experimental period, with average values of 25, 17, and 29 microgram/g liver respectively in the male rats, male hamsters and female hamsters. Chronic ethionine administration always suppressed hepatic AdoMet levels. This suppression was generally greater in animals fed the 0.1% ethionine than in those fed the 0.3% ethionine diet. Thus, the average hepatic AdoMet level in rats, male hamsters and female hamsters receiving the 0.1% ethionine diet for 3-6 weeks were 32, 18, and 45% respectively, of the corresponding AdoMet levels in control animals: however, the corresponding AdoMet levels in animals receiving the 0.3% ethionine diet were 66, 42, and 62% of the respective control values. Feeding 0.1% ethionine to male hamsters led to exceedingly low levels of liver AdoMet (1.4-2.9 microgram/g). No direct correlations could be made between the effects of ethionine feeding on the hepatic AdoEt and AdoMet levels in rats and hamsters and the previously reported differences in carcinogenicity by ethionine in these species.

Protective effect of diethylmaleate pretreatment on carbon tetrachloride hepatotoxicity

The administration of diethylmaleate (DEM) to fed and fasted rats produced a marked depletion of hepatic reduced glutathione (GSH) to 26 and 20% of respective saline control values 30 min after drug administration. When carbon tetrachloride (CCl 4) was administered to fasted animals pretreated with saline or DEM, the serum enzymes GOT, GPT, and ICDH were elevated 24 hr after intoxication, but the increases were greater in the saline-pretreated group ( p < 0.05). The administration of CCl 4 to fed animals produced elevations in serum GOT, GPT, and ICDH 24 hr after intoxication that were of similar magnitude in the saline- and DEM-pretreated groups ( p > 0.05). CCl 4 administration to fed rats produced altered hepatocellular architecture that was of similar magnitude in saline- and DEM-pretreated animals. However, in fasted animals, the histological changes following CCl 4 administration were more severe in saline-pretreated animals when compared to the DEM-pretreated group. The data suggest that DEM pretreatment exerts a protective effect against CCl 4-induced hepatic injury in fasted rats that may be related to the ability of DEM to inhibit hepatic microsomal drug metabolism.

Effect of oxaminiquine on pentobarbital-induced sleeping time in rats

Oxaminiquine (OMQ) injected intramuscularlyinrats prolonged the Pentobarbital (PNB) induced sleeping time by 76% over respective control values. This OMQ-effect was noticed at a significant level as long as 22 hr. after one administration of the antihelminthic. On the other hand, the approximate minimal dose of OMQ capable of prolonging the barbiturate effect was 12.5 mg/Kg.

The effect of acute hypoxia on synaptosomes from rat brain.

Abstract: Synaptosomes have been isolated from the brains of nonanesthetized and nembutal‐anesthetized rats subjected to 30 min hypoxia induced by breathing 7% oxygen in nitrogen. The respiratory rate was depressed in synaptosomes from starved hypoxic animals but was not significantly different from the respective control values in preparations from fed hypoxic animals, anesthetized animals, and hypoxic nonanesthetized animals allowed to recover from the hypoxic episode by 60 min of normoxic conditions. Observations are also reported concerning the levels of various metabolites in the synaptosomes isolated from the brains of the same groups of animals. It is suggested that hypoxia results in damage to the synaptosomal and/or mitochondrial membrane, which modifies substrate oxidation in the mitochondria and decreases availability of reducing equivalents for the respiratory chain. Results obtained on afflicted and recovered animals indicate that synaptosomal preparations provide a useful model for the study of hypoxic damage.

Changes in glucose-6-phosphatase activity in liver and kidney of rats treated with a single large dose of fluoride

Changes in glucose-6-phosphatase activities in the liver and kidney were investigated in rats after ip administration of a large dose of fluoride (NaF, 35 mg/kg body wt). The glucose-6-phosphatase activity in the liver and kidney of fluoride-treated rats increased 2.37 and 3.42 times that of respective control values. These elevations in hepatic and renal glucose-6-phosphatase activity were suppressed by pretreatments of actinomycin D or cycloheximide.

Inducing a possible state of senescence in developing barley seedlings by applying the α‐chloroacetamide propachlor

Summary:Propachlor (5, 50, 500 M) applied to the roots of barley (Hordeum vulgare L.) seedlings after 7 and 10 days, respectively, induces decreasing accumulation of fresh matter and dry matter; shoot length and root length are reduced. There was observed higher Hill activity, but lower O2‐evolution per unit dry weight and per seedling as calculated from Hill measurements. In the herbicide treated seedlings lower amounts of chlorophylls and carotenoids were found with decreasing ratios of chlorophylls/carotenoids and higher ratios of xanthophylls/β‐carotene. The ratios of chlorophyll a/benzoquinones decreased with regard to the control data. The accumulation of the single benzoquinones (on a chlorophyll basis), as related to the respective control values, is greater for α‐tocopherol, less for plastoquinone‐9 and even less for α‐tocoquinone. From the data obtained it is assumed that propachlor induces a state of senescence in the chloroplast. Propachlor seems to antagonize the known effects of exogenous indol‐3‐acetic acid. Questions of interaction of herbicide/phytohormone in this connection are discussed.

Effects of saturated and polyunsaturated fat diets on the chemical composition and metabolism of low density lipoproteins in man.

This study examined the effects of dietary saturated and polyunsaturated fat on the chemical composition and metabolism of low density lipoproteins (LDL) in eight normal male subjects. The influence of these diets on fecal sterol excretion was also measured in four of the subjects. When compared with the saturated fat diet, the polyunsaturated diet lowered both plasma cholesterol polyunsaturated diet lowered both plasma cholesterol (23%, P less than 0.001) and triglyceride (14%, P less than 0.001) levels. Sixty-seven percent of the reduction in the former lipid resulted from a fall in LDL cholesterol (23%, P less than 0.001), although very low density (VLDL) and high density lipoprotein (HDL) cholesterol levels also fell (by 27% and 20% of their respective control value). These changes were accompanied by significant alterations in LDL composition. Specifically, during polyunsaturated fat feeding, the relative percentage cholesterol in the LDL fraction fell while that of phospholipid rose. There was no change in the percentage protein or triglyceride. The fatty acid components of LDL triglyceride, cholesteryl esters, and phospholipid were also affected by dietary fat saturation level. Overall, polyunsaturated fat feeding produced an enrichment in linoleate with reciprocal changes in palmitate, stearate, and oleate which affected triglycerides more than cholesteryl esters and phospholipids. The above changes in LDL composition were associated with alterations in the metabolism of LDL apoprotein (apoLDL). The polyunsaturated deit lowered plasma apoLDL by 13% (P less than 0.05). This resulted from an increase in the fractional catabolic rate of LDL (whether determined by plasma decay curve analysis (P less than 0.05) or urine/plasma radioactivity ratios (P less than 0.001) without significant alteration of its corporeal distribution or synthetic rate. The polyunsaturated fat diet did not cause a consistent change in fecal neutral or acidic steroid excretion. We conclude that the hypocholesterolemic action of polyunsaturated fat diets is effected by multiple mechanisms whose expression may vary from patient to patient.

A method for determining the statistical significance of mutation frequencies

AbstractA method is devised for determining the statistical significance of the difference between a mutation frequency observed after treatment with a potential mutagen and its control frequency. This procedure, however, can be used only when the respective control value is based on large and reliable material (“stable” controls), a requirement that seems to be met in at least part of the systems used for mutagenesis screening. The procedure proposed has some advantages when compared with the 2 and the KASTENBAUM‐BOWMAN test, the most important one being that it can be employed when these two tests cannot (because of expected frequencies &lt;5 in the 2 test and limited tabulations of the N and p values in the KASTENBAUM‐BOWMAN test). After explaining the procedure, an instruction how to carry it out is presented and illustrated by two examples (recessive sex‐linked lethal mutations in Drosophila melanogaster and dicentric chromosomes in human lymphocytes).

Sex differences in biochemical manifestations of selenium deficiency in rat liver with special reference to heme metabolism

In addition to its well-known effect on glutathione peroxidase, selenium deficiency causes: (1) a defect in hepatic heme metabolism characterized by a phenobarbital-mediated increase in microsomal heme oxygenase activity, and (2) an increase in hepatic glutathione S-transferase activity. Since these effects were reported in selenium-deficient male rats, and since female rats have a lower selenium requirement than males, we examined whether these effects were sex-dependent. Weanling male rats, female rats, castrated male rats, and testosterone-treated female rats were fed either a selenium-deficient or a control diet. After 8 weeks, selenium-dependent hepatic glutathione peroxidase activity was 1 per cent of respective control values in each of the selenium-deficient groups. Hepatic glutathione, S-transferase activity was doubled by selenium deficiency in normal, unoperated males but was unaffected in the other groups. In control diet fed rats phenobarbital given as a single injection caused either no significant change or a decrease in the activity of hepatic microsomal heme oxygenase, the rate-limiting enzyme in heme degradation. In contrast, microsomal heme oxygenase activity was stimulated by phenobarbital in all selenium-deficient rats. The stimulation was greatest in males and least in females with intermediate values in castrated males and testosterone-treated females. These results demonstrate a marked effect of sex, castration of males, and testosterone treatment of females on the response of hepatic heme metabolism to phenobarbital and on glutathione S-transferase activity in selenium deficiency even though glutathione peroxidase was reduced to the same extent by selenium deficiency in all groups.

Changes in composition of chlorophylls, carotenoids, and prenylquinones in green seedlings of Hordeum and Raphanus induced by the herbicide San 6706—an effect possibly antagonistic to phytochrome action

The substituted pyridazinone herbicide San 6706 (4-chloro-5-(dimethylamino)-2-(α,α,α-trifluoro- m-tolyl)-3-(2 H)-pyridazinone) inhibits accumulation of chlorophylls and carotenoids to about the same degree in Hordeum and Raphanus seedlings under continuous illumination. Stronger inhibition of pigment accumulation in general is correlated with a stronger inhibition of the prenylquinones plastoquinone-9,α-tocopherol, and α-tocoquinone; but the amounts of inhibition are much lower for the prenylquinones. Such an inhibition pattern, which is observed in the two plants of different ages and when different herbicide concentrations are applied, points to a site of action which regulates the biosynthesis of these prenyllipids together. There is a different degree in the change of the relative proportions (percentages of herbicide-treated plants as related to the respective control values) of the single carotenoids induced by the herbicide. In this sense there was the highest increase for zeaxanthin and lowest for β-carotene both in Hordeum and Raphanus. The order of relative change of the carotenoids analyzed is about the same as in etiolated barley seedlings of equal age illuminated with white light—but with an opposite sign. The relative proportions of the benzoquinones might be changed in an analogous way. It is suggested, that with respect to carotenoid synthesis and perhaps also benzoquinone synthesis San 6706 acts on the same reaction chain like phytochrome but in an antagonistic way, possibly at the cytoplasmic ribosomes.

Cardiopulmonary changes in the crying neonate.

To determine hemodynamic effects of crying, 12 newborn infants recovering from the respiratory distress syndrome (RDS) were studied. When crying, the range of inspiratory esophageal pressure was -18.8 to -32.5 cm H2O and the range of espiratory pressure was +6.2 to 34.4 cm H2O. The esophageal pressure remained positive for a mean value of 66% of the respiratory cycle. There was a mean significant increase in heart rate of 19 beats/min. The systolic and diastolic blood pressures increased significantly at the beginning of strain to 115 and 135% of the respective control values. There was a progressive decrease in systolic and diastolic pressures during the period of strain and the systolic pressures reached values significantly less than control. With the decrease in systolic and diastolic pressures, there were pronounced reductions in pulse pressures. Three infants reached pulse pressure values less than 1% of control when cries were sustained for nine cardiac cycles. There was a significant mean decrease in arterial oxygen tension (PaO2) of 16.8 mm Hg. There were no changes in arterial carbon dioxide tension (PaCO2), pH, or base excess.

Echocardiographic analysis of human left ventricular diastolic volume and cardiac performance during halothane anesthesia.

Using M-mode echocardiography we found that 0.5, 1.0, and 1.5% end-tidal halothane induced dose-related increases in left ventricular volume and decreases in left ventricular performance in seven normal unpremedicated subjects. During controlled respiration with normocarbia, the diastolic minor axis of the heart, which is related to the cube root of left ventricular volume, increased to a maximum of 107. 7 +/- 1.9 (% +/- SE of control) at 1.5% end-tidal halothane from a control value of 43.5 +/- 1.3 (mm +/- SE). Two ejection-phase performance variables, percentage shortening and mean velocity of circumferential shortening decreased to 60.1 +/- 6.1 (% +/- SE of control) and 62.4 +/- 6.5, (% +/- SE of control) at 1.5% halothane from respective control values of 29.7 +/- 2.61 (% +/- SE) and 0.94 +/- 0.08 (circumferences/second +/- SE). Surgical stimulation did not significantly affect these changes. Under these experimental conditions, we conclude that halothane dilates the heart, and that echocardiography can be used to monitor the depressant effect of halothane on the heart.

Testosterone and Testosterone Binding Globulin (TeBG) in Young Men during Prolonged Stress

The effect of prolonged physical and psychological stress on the testicular function was studied in 8 students (age 22–25 years) of the Norwegian Academy of War during a combat course of 5 days' duration. The average urinary excretion of free cortisol and 17‐ketogenic steroids was 81 and 129% higher than the respective control values one week after the course. Plasma cortisol levels increased from 21.7 μg/100 ml at 8 a. m. before the course to 24.6 (P &lt; 0.05), and serum HGH rose from undetectable levels, &lt; 0.08 ng/ml, to an average value of 12.9 ng/ml ± 3.7 (SD) at 8 a. m. during the course.A marked suppressive effect on plasma testosterone levels from 5.6 ng/ml ± 1.4 to 0.9 ± 0.5, and no adjustment to stress was observed over a 5 day period. TeBG increased gradually from 26.9 nmol/l ± 9.9 to 52.7 ± 17.7 on day 6, followed by a slow decrease without reaching control values on day 12, suggesting that the decreased plasma testosterone levels probably reflect reduced production and not increased metabolism of testosterone. LH fluctuated during the course, but was significantly higher in the morning immediately following the end of the course than at the start (P &lt; 0.02). It is postulated that the effect of stress on the plasma testosterone levels is mediated via an action both on the hypothalamus‐pituitary level and on the testis.

Systemic hemodynamics in nephrotoxic acute renal failure.

Cardiac output (CO) and renal blood flow (RBF) were simultaneously evaluated (microsphere method) in awake rats, 3, 6, and 24 h after induction of acute renal failure by mercuric chloride (HgCl2; 4.7 mg/kg body weight). 3 h after injection of HgCl2, CO and RBF decreased to 77 and 72% of respective control values of 32.0 +/- 2.4 and 4.65 +/- 0.44 ml/min/100 g. Renal vascular resistance (RVR) and total peripheral resistance (TPR) were significantly increased compared to control at this time. Similar results were observed 6 h after administration of HgCl2. Volume expansion with plasma (2% of body weight) restored CO, RBF, TPR, and RVR to normal 3 h after injection of HgCl2. Despite significantly elevated blood urea nitrogen 24h after injection of HgCl2 (103.7 mg%), all hemodynamic parameters were within control range. Plasma volume was normal 3 h after HgCl2 but was significantly elevated compared to control 24 h after HgCl2 (4.73 vs. 3.92 ml/100 g, p less than 0.01). These findings indicate that factors other than preferential renal vasoconstriction may be involved in the transient renal ischemia of HgCl2-induced acute renal failure.

Effect of glucagon on metabolite compartmentation in isolated rat liver cells during gluconeogenesis from lactate

1. The subcellular distribution of adenine nucleotides, acetyl-CoA, CoA, glutamate, 2-oxoglutarate, malate, oxaloacetate, pyruvate, phosphoenolpyruvate, 3-phosphoglycerate, glucose 6-phosphate, aspartate and citrate was studied in isolated hepatocytes in the absence and presence of glucagon by using a modified digitonin procedure for cell fractionation. 2. In the absence of glucagon, the cytosol contains about two-thirds of cellular ATP, some 40-50% of ADP, acetyl-CoA, citrate and phosphoenolpyruvate, more than 75% of total 2-oxoglutarate, glutamate, malate, oxaloacetate, pyruvate, 3-phosphoglycerate and aspartate, and all of glucose 6-phosphate. 3. In the presence of glucagon the cytosolic space shows an increase in the content of malate, phosphoenolpyruvate and 3-phosphoglycerate by more than 60%, and those of aspartate and glucose 6-phosphate rise by about 25%. Other metabolites remain unchanged. After glucagon treatment, cytosolic pyruvate is decreased by 37%, whereas glutamate and 2-oxoglutarate decrease by 70%. The [NAD(+)]/[NADH] ratios calculated from the cytosolic concentrations of the reactants of lactate dehydrogenase and malate dehydrogenase were the same. Glucagon shifts this ratio and also that of the [NADP(+)]/[NADPH] couple towards a more reduced state. 4. In the mitochondrial space glucagon causes an increase in the acetyl-CoA and ATP contents by 25%, and an increase in [phosphoenolpyruvate] by 50%. Other metabolites are not changed by glucagon. Oxaloacetate in the matrix is only slightly decreased after glucagon, yet glutamate and 2-oxoglutarate fall to about 25% of the respective control values. The [NAD(+)]/[NADH] ratios as calculated from the [3-hydroxybutyrate]/[acetoacetate] ratio and from the matrix [malate]/[oxaloacetate] couple are lowered by glucagon, yet in the latter case the values are about tenfold higher than in the former. 5. Glucagon and oleate stimulate gluconeogenesis from lactate to nearly the same extent. Oleate, however, does not produce the changes in cellular 2-oxoglutarate and glutamate as observed with glucagon. 6. The changes of the subcellular metabolite distribution after glucagon are compatible with the proposal that the stimulation of gluconeogenesis results from as yet unknown action(s) of the hormone at the mitochondrial level in concert with its established effects on proteolysis and lipolysis.