Action of α-methyl-DL-tryptophan in vivo on catabolism of amino acids and their conversion to liver glycogen

1969 ◽  
Vol 47 (2) ◽  
pp. 179-184 ◽  
Author(s):  
M. Oravec ◽  
T. L. Sourkes
Keyword(s):  
Carbon Dioxide ◽  
Amino Acids ◽  
Body Temperature ◽  
Adrenal Glands ◽  
Liver Glycogen ◽  
Hepatic Glycogen ◽  
Stimulatory Action ◽  
Tryptophan Pyrrolase ◽  
Adrenalectomized Rats

AMTP (α-methyl-DL-tryptophan) stimulates the incorporation of (labeled) alanine, glutamate, leucine, isoleucine, histidine, threonine, tryptophan, pyruvate, and acetate into hepatic glycogen. Accompanying this phenomenon is an enhanced rate of oxidation of these substances to carbon dioxide, except for acetate whose oxidation is not influenced by AMTP. AMTP also causes an increased excretion of urea and a rise in body temperature. Presence of the adrenal glands is necessary for the stimulatory action of AMTP on the oxidation of alanine, glutamate, isoleucine, and pyruvate. AMTP-stimulated oxidation of leucine and threonine is only partially dependent upon the adrenal gland. The oxidation of histidine is increased to the same extent by AMTP in both intact and adrenalectomized rats. The ability of AMTP to increase the level of tryptophan pyrrolase activity and, thereby, to create an imbalance of the proportion of amino acids in the rat is implicated in the mechanism responsible for its glyconeogenic property and ability to increase catabolism of amino acids.

scholarly journals Glycogen synthesis in the perfused liver of adrenalectomized rats

1976 ◽  
Vol 156 (3) ◽  
pp. 585-592 ◽  
Author(s):  
P D Whitton ◽  
D A Hems
Keyword(s):  
Intact Animal ◽  
Glycogen Synthesis ◽  
Hepatic Metabolism ◽  
Hepatic Glycogen ◽  
Perfused Liver ◽  
Short Term ◽  
Glycogen Accumulation ◽  
Glycogen Deposition ◽  
Adrenalectomized Rats

1. A total loss of capacity for net glycogen synthesis was observed in experiments with the perfused liver of starved adrenalectomized rats. 2. This lesion was corrected by insulin or cortisol in vivo (over 2-5h), but not by any agent tested in perfusion. 3. The activity of glycogen synthetase a, and its increase during perfusion, in the presence of glucose plus glucogenic substrates, were proportional to the rate of net glycogen accumulation. 4. This complete inherent loss of capacity for glycogen synthesis after adrenalectomy is greater than any defect in hepatic metabolism yet reported in this situation, and is not explicable by a decrease in the rate of gluconegenesis (which supports glycogen synthesis in the liver of starved rats). The short-term (2-5h) stimulatory effect of glucocorticoids in the intact animal, on hepatic glycogen deposition, may be mediated partly through insulin action, although neither insulin or cortisol appear to act directly on the liver to stimulate glycogen synthesis.

PAF increases hepatic vascular resistance and glycogenolysis in vivo

1991 ◽  
Vol 260 (3) ◽  
pp. G471-G480 ◽  
Author(s):  
K. L. Hines ◽  
A. Braillon ◽  
R. A. Fisher
Keyword(s):  
Blood Flow ◽  
Blood Glucose ◽  
Glucose Concentration ◽  
Glycogen Phosphorylase ◽  
Blood Glucose Concentration ◽  
Portal Pressure ◽  
Hepatic Glycogen ◽  
Hepatic Portal ◽  
Adrenalectomized Rats

Administration of platelet-activating factor (PAF) to portal venous circulation of anesthetized fed rats produced decreases in mean arterial pressure and increases in hepatic portal pressure and blood glucose concentration. These responses to PAF were dose dependent with ED50 values of 0.02-0.05 micrograms/kg and specific as lyso- and enantio-PAF did not reproduce effects of PAF. Specific PAF receptor antagonist SRI 63-675 (75 micrograms/kg) inhibited significantly these PAF (0.1 micrograms/kg)-induced responses in rats. Administration of prazosin (500 micrograms/kg) and propranolol (400 micrograms/kg) to rats abolished phenylephrine (50 micrograms/kg)-induced increases in mean arterial pressure, hepatic portal pressure, and blood glucose concentration but did not prevent PAF (1 microgram/kg)-induced alterations in these parameters. Glycogen phosphorylase alpha levels were increased significantly in livers of rats after administration of PAF (1 microgram/kg) or phenylephrine (50 micrograms/kg). Administration of prazosin and propranolol to rats inhibited phenylephrine- but not PAF-induced activation of hepatic glycogen phosphorylase. Hepatic adenosine 3',5'-cyclic monophosphate (cAMP) concentration was increased slightly by PAF, but these increases were eliminated by adrenergic blockade, suggesting that activation of hepatic glycogen phosphorylase by PAF is not dependent on increases in cAMP. Increases in hepatic portal pressure and blood glucose concentration in response to PAF (0.1 micrograms/kg) were not attenuated in adrenalectomized rats. Moreover, PAF (0.1 micrograms/kg) stimulated increases in hepatic portal pressure after administration of the ganglionic blocking agent chlorisondamine (2.5 mg/kg) to adrenalectomized rats. Administration of PAF (0.05 micrograms/kg) to rats instrumented with pulse Doppler flow probes produced decreases in hepatic arterial and portal vein blood flow and increases in hepatic arterial and portal vascular resistance. These observations provide direct evidence that PAF regulates hepatic hemodynamics and glycogenolysis in vivo. It is suggested that PAF plays an important role in regulating hepatic blood flow and supplying extrahepatic tissues with energy substrates by sympathetic-independent mechanism(s) after its release in acute pathophysiological situations.

Mechanism of delayed hepatic glycogen synthesis after an oral galactose load vs. an oral glucose load in adult rats

1992 ◽  
Vol 263 (1) ◽  
pp. E42-E49 ◽  
Author(s):  
C. B. Niewoehner ◽  
B. Neil
Keyword(s):  
Glucose Concentration ◽  
Glycogen Synthesis ◽  
Liver Glycogen ◽  
Hepatic Glycogen ◽  
Oral Glucose ◽  
Glucose Load ◽  
Adult Rats ◽  
Glycogen Accumulation ◽  
Glucose Administration

We have compared the effects of administration of oral galactose or glucose (1 g/kg) to 24-h fasted rats to examine the mechanism by which galactose regulates its own incorporation into liver glycogen in vivo. Liver glycogen increased to a maximum more slowly after galactose than after glucose administration (0.14 vs. 0.29 mumol.g liver-1.min-1). Glycogen accumulation after the galactose load was 70% of that after the glucose load (149 vs. 214 mumol), and the net increase in liver glycogen represented the same proportion (24 vs. 22%) of added carbohydrate after urinary loss of galactose was accounted for. Slower glycogen accumulation after galactose vs. glucose loading could not be explained by galactosuria, by differences in the active forms of synthase or phosphorylase, by end product (glycogen) inhibition of synthase phosphatase, or by different concentrations of the known allosteric effectors of synthase R plus I and phosphorylase a. Similar increases in glucose 6-phosphate were observed after both hexoses. AMP and ADP increased only transiently after galactose administration, and ATP, UTP, and Pi concentrations were unchanged. The UDP-glucose concentration decreased, whereas the UDP-galactose concentration increased two- to threefold after galactose but not glucose administration. The UDP-glucose pyrophosphorylase reaction is inhibited competitively by UDP-galactose. This could explain the decreased UDP-glucose concentration and the reduced rate of glycogen synthesis after galactose was given.

Measurement of hepatic Ra UDP-glucose in vivo in rats: relation to glycogen deposition and labeling patterns

1997 ◽  
Vol 272 (1) ◽  
pp. E155-E162 ◽  
Author(s):  
M. K. Hellerstein ◽  
A. Letscher ◽  
J. M. Schwarz ◽  
D. Cesar ◽  
C. H. Shackleton ◽  
...  
Keyword(s):  
Liver Glycogen ◽  
Hepatic Glycogen ◽  
Distribution Analysis ◽  
Basic Principles ◽  
Intravenous Glucose ◽  
Isotopic Method ◽  
Mass Isotopomer Distribution Analysis ◽  
Common Precursor ◽  
Glycogen Deposition

We previously described an isotopic method for quantifying the rate of appearance of hepatic UDP-glucose (Ra UDP-Glc) and the direct entry of glucose into hepatic UDP-Glc in humans. Here, the method is tested in depth in rats. The basic principles are that dilution of labeled galactose in hepatic UDP-Glc, sampled noninvasively by the xenobiotic glucuronate (GlcUA) method, reveals Ra UDP-Glc. First, labeling patterns in secreted acetaminophen-GlcUA were compared with hepatic glycogen and plasma glucose by use of mass isotopomer distribution analysis from [2-(13)C]glycerol. Labeling was consistent with common precursor pools of glucose 6-phosphate and triose-phosphate for all end products studied in fasted and in intravenous glucose- and fructose-infused states. Next, [1-(3)H]galactose was administered. After a 24-h fast, Ra UDP-Glc was 25.0 +/- 1.7 mumol.kg body wt-1.min-1 and rose to 57.7 and 72.7 mumol.kg-1.min-1 at intravenous glucose infusion rates of 111 and 167-194 mumol.kg-1.min-1, respectively. Liver glycogen deposition correlated closely with Ra UDP-Glc (R2 = 0.76), although the turnover value was approximately 50% higher than the net deposition rate. In conclusion, the turnover of an intrahepatic metabolite, UDP-Glc, can be measured noninvasively, and Ra UDP-Glc correlates with liver glycogen deposition in rats.

scholarly journals Overexpression of β2-adrenergic receptors in mouse liver alters the expression of gluconeogenic and glycolytic enzymes

2005 ◽  
Vol 288 (4) ◽  
pp. E715-E722 ◽  
Author(s):  
Loubna Erraji-Benchekroun ◽  
Dominique Couton ◽  
Catherine Postic ◽  
Isabelle Borde ◽  
Jesintha Gaston ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Adenylyl Cyclase ◽  
Adrenergic Receptors ◽  
Mammalian Species ◽  
Physiological Role ◽  
Glucose Production ◽  
Liver Glycogen ◽  
Hepatic Glycogen ◽  
Physiological Conditions

In the livers of humans and many other mammalian species, β2-adrenergic receptors (β2-ARs) play an important role in the modulation of glucose production by glycogenolysis and gluconeogenesis. In male mice and rats, however, the expression and physiological role of hepatic β2-ARs are rapidly lost with development under normal physiological conditions. We previously described a line of transgenic mice, F28 (André C, Erraji L, Gaston J, Grimber G, Briand P, and Guillet JG. Eur J Biochem 241: 417–424, 1996), which carry the human β2-AR gene under the control of its own promoter. In these mice, hepatic β2-AR levels are shown to increase rapidly after birth and, as in humans, be maintained at an elevated level in adulthood. F28 mice display strongly enhanced adenylyl cyclase responses to β-AR agonists in their livers and, compared with normal mice, have increased basal hepatic adenylyl cyclase activity. In this report we demonstrate that, under normal physiological conditions, this increased β2-AR activity affects the expression of the gluconeogenic and glycolytic key enzymes phospho enolpyruvate carboxykinase, glucose-6-phosphatase, and l-pyruvate kinase and considerably decreases hepatic glycogen levels. Furthermore, we show that the effects of β-adrenergic ligands on liver glycogen observed in humans are reproduced in these mice: liver glycogen levels are strongly decreased by the β2-AR agonist clenbuterol and increased by the β-AR antagonist propranolol. These transgenic mice open new perspectives for studying in vivo the hepatic β2-AR system physiopathology and for testing the effects of β-AR ligands on liver metabolism.

scholarly journals Effects of adrenalectomy before weaning in the genetically obese Zucker rat (fa/fa)

1986 ◽  
Vol 56 (1) ◽  
pp. 141-151 ◽  
Author(s):  
J. M. Fletcher
Keyword(s):  
Body Composition ◽  
Lipid Content ◽  
Plasma Concentrations ◽  
Liver Glycogen ◽  
Tyrosine Aminotransferase ◽  
Zucker Rats ◽  
Hepatic Glycogen ◽  
Phenotypic Differences ◽  
Reduced Body ◽  
Adrenalectomized Rats

1. Lean (Fa/?) and obese (fa/fa) Zucker rats were adrenalectomized or sham-operated at 19 d of age (3 d before weaning). Injection of corticosterone for 3 d after weaning (1.0 mg/d) was necessary to ensure survival of adrenalectomized fa/fa but not Fa/? rats. Intact and adrenalectomized fa/fa rats had a lower rectal temperature than Fa/? animals before and 3 d after adrenalectomy. The post-weaning survival of adrenalectomized fa/fa rats was enhanced by maintenance at an ambient temperature of 30° rather than 22°.2. Adrenalectomized and sham-operated rats were therefore kept at 30°, fed ad-lib. and killed at 34 d. Adrenalectomy had only small effects on the growth, body composition and appetite of Fa/? rats. The hyperphagia, greater lipid content, reduced protein content and hyperinsulinaemia of fa/fa rats were completely abolished by adrenalectomy.3. Intact fu/fa rats had higher liver glycogen contents and higher activities of the hepatic enzymes tyrosine aminotransferase (EC 2. 6. 1. 5) and acetyl CoA carboxylase (EC 6. 4. 1. 2) than intact Fa/? animals. Adrenalectomy abolished these phenotypic differences.4. Injection of adrenalectomized rats with 1.0 mg corticosterone-21-acetate daily from weaning to 34 d restored the abnormal body composition, hyperphagia, hyperinsulinaemia, higher hepatic glycogen and enzyme activities of fa/fa rats.5. In a second experiment adrenalectomized rats were injected with 1.0 mg corticosterone-21-acetate daily from weaning to 34 d and kept at 22°, fa/fu rats adrenalectomized and injected with corticosterone had a reduced body lipid content compared with intact fa/fa rats but still contained more lipid than intact or similarly treated Fa/? animals.6. In both experiments adrenalectomized Fa/? and fa/fa rats injected daily with corticosterone had the same plasma concentrations of this hormone when killed 3 h after the last injection at 34 d. It is concluded that corticosterone is required for expression of the abnormal appetite, hyperinsulinaemia and body composition of the fa/fa rat.

MAINTENANCE OF BODY TEMPERATURE OF RESTRAINED ADRENALECTOMIZED RATS EXPOSED TO COLD: EFFECT OF ADRENAL CORTICAL HORMONES

1956 ◽  
Vol 34 (4) ◽  
pp. 721-729
Author(s):  
P. F. Iampietro ◽  
M. J. Fregly ◽  
E. R. Buskirk
Keyword(s):  
Body Temperature ◽  
Cooling Rate ◽  
Adrenal Glands ◽  
Cold Effect ◽  
Desoxycorticosterone Acetate ◽  
Pass Through ◽  
Colonic Temperature ◽  
Higher Doses ◽  
Adrenalectomized Rats

Experiments were performed to determine the role of the adrenal glands in the maintenance of colonic temperature of rats which were restrained and exposed to air at 5 °C. Colonic temperature decreased linearly with time in the cold air; hence, colonic cooling rate (CCR) was adopted as a measure of response to cold. Bilateral adrenalectomy increased CCR. Administration of cortisone acetate, adrenal cortical extract (ACE) or desoxycorticosterone acetate to adrenalectomized rats decreased CCR. Maximal decrease occurred with administration of 1.00 mgm. cortisone/rat/day or 0.25 ml. ACE/rat/day; higher doses of each hormone were less and less effective in returning CCR toward that of sham-operated rats. An adrenalectomized rat could not be rendered normal with respect to CCR no matter what dose of either ACE or cortisone was administered. In contrast, only the highest dose of DOCA administered (4.0 mgm./rat/day) significantly reduced CCR to that of sham-operated rats. The cooling test is similar to the standard growth test in that the response to administration of cortisone and ACE passes through a maximum and then declines with increasing dosage. The lower colonic temperature of adrenalectomized rats in air at 25 °C. was returned to that of sham-operated rats when cortisone (1.00 mgm. or more) or ACE (0.25 ml. or more) was administered; however, colonic temperature did not appear either to increase incrementally or to pass through a maximum with increasing doses of either hormone. DOCA had no effect on initial colonic temperature. Untreated adrenalectomized rats rarely survived lowering of colonic temperature to 22.5 °C; hence, the minimum colonic temperature to which adrenalectomized rats can be cooled and subsequently survive is considerably above that for normal rats (LD50 15.3 °C). Administration of any of the above hormones increased survival even in those doses which did not affect CCR.

The mechanism by which glucagon induces the release of amino acids from muscle and its relevance to fasting

1977 ◽  
Vol 196 (1124) ◽  
pp. 347-365 ◽  
Keyword(s):  
Amino Acids ◽  
Blood Glucose ◽  
Skeletal Muscles ◽  
Muscle Protein ◽  
Liver Glycogen ◽  
Blood Levels ◽  
Hepatic Glycogen ◽  
Systemic Injection ◽  
Arterial Blood ◽  
Glucose Synthesis

A raised level of glucagon was attained rapidly, and maintained steadily, for an hour or more in the circulation of fed, or of fasted, rabbits. During this time the concentrations of 18 amino acids, of glucose and of insulin, were measured in samples of arterial blood and of blood leaving the skeletal muscles, taken simultaneously. The glucagon raised the level of glucose in the arterial blood, while, at the same time, decreasing the levels of most of the amino acids. The rate of release of amino acids from the skeletal muscles increased during this time. When the store of hepatic glycogen had been depleted by a previous injection of glucagon, or by fasting, glucagon still caused a rise in blood glucose, but the rise was less, and was less well sustained, than that seen when the glycogen stores of the liver were normal. The second injection of glucagon, or fasting, caused the glycogen depleted liver to convert certain amino acids, obtained from the blood, into glucose, lowering the blood levels of these amino acids. The muscles now released amino acids. There was no detectable difference in the release of amino acids from muscle whether glucagon was given systemically or into the artery supplying the muscles. However, a systemic injection of L-alanine, together with glucagon, abolished the fall in the level of amino acids in the blood, and suppressed their release from muscle. During fasting a steady fall in the blood levels of five amino acids occurred, probably due to their use by the liver for glucose synthesis; the temporary rise in the levels of other amino acids, which are not readily used for glucose synthesis, seems to be due to their concomitant release, from the breakdown of muscle protein. We conclude that the elevated level of glucagon, which is found in fasting, ensures that an acceptable level of the blood glucose is maintained by means of two mechanisms; first by releasing glucose from liver glycogen, and then, when fasting is prolonged, by causing the liver to synthesize glucose from certain of the amino acids in the blood, thus decreasing their concentration in the blood. This fall in the levels of these amino acids in the blood is, we believe, the stimulus which leads first to the release of amino acids from the muscles, and then to the breakdown of muscle protein to replace these released amino acids, and thus to maintain a continuous supply of these amino acids for glucose synthesis.

MAINTENANCE OF BODY TEMPERATURE OF RESTRAINED ADRENALECTOMIZED RATS EXPOSED TO COLD: EFFECT OF ADRENAL CORTICAL HORMONES

1956 ◽  
Vol 34 (1) ◽  
pp. 721-729 ◽  
Author(s):  
P. F. Iampietro ◽  
M. J. Fregly ◽  
E. R. Buskirk
Keyword(s):  
Body Temperature ◽  
Cooling Rate ◽  
Adrenal Glands ◽  
Cold Effect ◽  
Desoxycorticosterone Acetate ◽  
Pass Through ◽  
Colonic Temperature ◽  
Higher Doses ◽  
Adrenalectomized Rats

Experiments were performed to determine the role of the adrenal glands in the maintenance of colonic temperature of rats which were restrained and exposed to air at 5 °C. Colonic temperature decreased linearly with time in the cold air; hence, colonic cooling rate (CCR) was adopted as a measure of response to cold. Bilateral adrenalectomy increased CCR. Administration of cortisone acetate, adrenal cortical extract (ACE) or desoxycorticosterone acetate to adrenalectomized rats decreased CCR. Maximal decrease occurred with administration of 1.00 mgm. cortisone/rat/day or 0.25 ml. ACE/rat/day; higher doses of each hormone were less and less effective in returning CCR toward that of sham-operated rats. An adrenalectomized rat could not be rendered normal with respect to CCR no matter what dose of either ACE or cortisone was administered. In contrast, only the highest dose of DOCA administered (4.0 mgm./rat/day) significantly reduced CCR to that of sham-operated rats. The cooling test is similar to the standard growth test in that the response to administration of cortisone and ACE passes through a maximum and then declines with increasing dosage. The lower colonic temperature of adrenalectomized rats in air at 25 °C. was returned to that of sham-operated rats when cortisone (1.00 mgm. or more) or ACE (0.25 ml. or more) was administered; however, colonic temperature did not appear either to increase incrementally or to pass through a maximum with increasing doses of either hormone. DOCA had no effect on initial colonic temperature. Untreated adrenalectomized rats rarely survived lowering of colonic temperature to 22.5 °C; hence, the minimum colonic temperature to which adrenalectomized rats can be cooled and subsequently survive is considerably above that for normal rats (LD50 15.3 °C). Administration of any of the above hormones increased survival even in those doses which did not affect CCR.

scholarly journals Effects in vivo of food deprivation and 3-mercaptopicolinate in the glycogen-storage-disease (gsd/gsd) rat

1985 ◽  
Vol 231 (3) ◽  
pp. 755-759 ◽  
Author(s):  
D G Clark ◽  
M Brinkman ◽  
S D Neville ◽  
W D Haynes
Keyword(s):  
Blood Glucose ◽  
Food Deprivation ◽  
Intraperitoneal Injection ◽  
Storage Disease ◽  
Liver Glycogen ◽  
Glycogen Storage ◽  
Hepatic Glycogen ◽  
Glycogen Stores ◽  
Female Control

Intraperitoneal injection of 3-mercaptopicolinate into 24 h-food-deprived 27-week-old female control (GSD/GSD) rats lowered the concentration of circulating glucose by 66%, but glycerol and lactate concentrations were increased up to 3- and 4-fold respectively. In phosphorylase b kinase-deficient (gsd/gsd) rats the corresponding changes for blood glucose, lactate and glycerol were half those observed in the controls. Although the concentration of liver glycogen (approx. 12%, w/w) in the gsd/gsd rats was not altered during food deprivation, total hepatic glycogen was decreased by 17%. It is suggested that the gradual breakdown of the extensive hepatic glycogen stores during starvation assists in the maintenance of normoglycaemia in the gsd/gsd rat.

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