Hormonal sensitivity and responsiveness in sea raven hepatocytes: changes with fasting and collagenase exposure

1993 ◽  
Vol 71 (9) ◽  
pp. 1755-1762 ◽  
Author(s):  
Glen D. Foster ◽  
T. W. Moon
Keyword(s):  
Carbohydrate Metabolism ◽  
Glucose Production ◽  
Sea Raven ◽  
High Insulin ◽  
Collagenase Perfusion ◽  
Hepatocyte Metabolism ◽  
Gluconeogenesis From Alanine ◽  
Total Glucose ◽  
Glucagon And Insulin ◽  
Hemitripterus Americanus

Changes in the apparent sensitivity and responsiveness of carbohydrate metabolism to glucagon and insulin were examined in hepatocytes isolated from fed and 6-week-fasted sea ravens (Hemitripterus americanus), with and without collagenase. The fasted group demonstrated higher rates of total glucose production (TGP) and gluconeogenesis from alanine than the fed group. Metabolic sensitivity to glucagon was increased with fasting, while the maximal responsiveness to both hormones was decreased with fasting; this latter effect may result from elevated control rates in the fasted group. Glucagon increased CO2 production from alanine in the fed group and decreased it in the fasted group. Insulin antagonized the effects of glucagon with respect to TGP and CO2 production, while the effects of the two hormones on gluconeogenesis were additive at high insulin concentrations in the fasted group. Hepatocytes isolated without collagenase perfusion had lower TGP, decreased sensitivity to glucagon, and decreased responsiveness to insulin than cells prepared with collagenase. Furthermore, the additive effects of insulin and glucagon on gluconeogenesis were not apparent when cells were isolated in the absence of collagenase. These results indicate that the response of hepatocyte carbohydrate metabolism to glucagon and insulin is affected by nutritional status, and that collagenase preparation significantly affects sea raven hepatocyte metabolism.

Effect of somatostatin on glucose homeostasis in conscious long-fasted dogs

1987 ◽  
Vol 253 (4) ◽  
pp. E435-E442 ◽  
Author(s):  
R. W. Stevenson ◽  
K. E. Steiner ◽  
G. K. Hendrick ◽  
A. D. Cherrington
Keyword(s):  
Carbohydrate Metabolism ◽  
Plasma Insulin ◽  
Control Period ◽  
Glucose Production ◽  
Glucose Levels ◽  
Glucose Clearance ◽  
Before And After ◽  
Initial Control ◽  
Lactate Uptake ◽  
Total Glucose

The effects of somatostatin plus intraportal insulin and glucagon replacement (pancreatic clamp) on carbohydrate metabolism were studied in conscious dogs fasted for 7 days so that gluconeogenesis was a major contributor to total glucose production. By use of [3-3H]glucose, glucose production (Ra) and utilization (Rd) and glucose clearance were assessed before and after implementation of the pancreatic clamp. After an initial control period, somatostatin (0.8 microgram . kg-1 . min-1) was infused with intraportal replacement amounts of glucagon (0.42 ng . kg-1 . min-1) and insulin. The insulin infusion rate was varied to maintain euglycemia and then kept constant (68 +/- 16 microU . kg-1 . min-1) for 250 min. Plasma glucagon was similar (84 +/- 14 and 89 +/- 19 pg/ml) before and during somatostatin infusion, while plasma insulin was lower (9.3 +/- 0.9 and 6.6 +/- 0.5 microU/ml, P less than 0.05). Plasma glucose levels remained similar (89 +/- 2 and 96 +/- 9 mg/dl), while Ra and Rd and the ratio of glucose clearance to plasma insulin were significantly (P less than 0.05) increased (from 2.18 +/- 0.12 to 3.21 +/- 0.35 and 2.30 +/- 0.09 to 3.26 +/- 0.38 mg . kg-1 . min-1, and 0.30 +/- 0.03 to 0.59 +/- 0.11, respectively). Net hepatic lactate uptake and [14C]alanine plus [14C]lactate conversion to [14C]glucose increased (P greater than 0.05) (from 9.32 +/- 0.47 to 16.54 +/- 2.97 mumol . kg-1 . min-1 and 100 to 263 +/- 37%, respectively). In conclusion, somatostatin alters glucose clearance in 7-day fasted dogs, resulting in changes in several indices of carbohydrate metabolism.

Branched-chain amino acid supplementation during bed rest: effect on recovery

2003 ◽  
Vol 94 (4) ◽  
pp. 1345-1352 ◽  
Author(s):  
T. P. Stein ◽  
M. R. Donaldson ◽  
M. J. Leskiw ◽  
M. D. Schluter ◽  
D. W. Baggett ◽  
...  
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Glucose Production ◽  
Bed Rest ◽  
Recovery Phase ◽  
Whole Body ◽  
N Retention ◽  
Gluconeogenesis From Alanine ◽  
Total Glucose

Bed rest is associated with a loss of protein from the weight-bearing muscle. The objectives of this study are to determine whether increasing dietary branched-chain amino acids (BCAAs) during bed rest improves the anabolic response after bed rest. The study consisted of a 1-day ambulatory period, 14 days of bed rest, and a 4-day recovery period. During bed rest, dietary intake was supplemented with either 30 mmol/day each of glycine, serine, and alanine ( group 1) or with 30 mmol/day each of the three BCAAs ( group 2). Whole body protein synthesis was determined with U-15N-labeled amino acids, muscle, and selected plasma protein synthesis withl-[2H5]phenylalanine. Total glucose production and gluconeogenesis from alanine were determined with l-[U-13C3]alanine and [6,6-2H2]glucose. During bed rest, nitrogen (N) retention was greater with BCAA feeding (56 ± 6 vs. 26 ± 12 mg N · kg−1 · day−1, P < 0.05). There was no effect of BCAA supplementation on either whole body, muscle, or plasma protein synthesis or the rate of 3-MeH excretion. Muscle tissue free amino acid concentrations were increased during bed rest with BCAA (0.214 ± 0.066 vs. 0.088 ± 0.12 nmol/mg protein, P < 0.05). Total glucose production and gluconeogenesis from alanine were unchanged with bed rest but were significantly reduced ( P < 0.05) with the BCAA group in the recovery phase. In conclusion, the improved N retention during bed rest is due, at least in part, to accretion of amino acids in the tissue free amino acid pools. The amount accreted is not enough to impact protein kinetics in the recovery phase but does improve N retention by providing additional essential amino acids in the early recovery phase.

scholarly journals Metabolic effects of cortisol treatment in a marine teleost, the sea raven

1996 ◽  
Vol 199 (7) ◽  
pp. 1509-1514
Author(s):  
M M Vijayan ◽  
T P Mommsen ◽  
H C Glémet ◽  
T W Moon
Keyword(s):  
Fatty Acid ◽  
Amino Acid ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Coconut Oil ◽  
Glucose Production ◽  
Tyrosine Aminotransferase ◽  
Metabolic Effects ◽  
Hepatic Glycogen ◽  
Sea Raven ◽  
Hemitripterus Americanus

Sea raven (Hemitripterus americanus) given intraperitoneal implants of coconut oil containing cortisol (50 mg kg-1) and sampled 5 days later had plasma cortisol, glucose and urea concentrations higher than in a sham-implanted group. No differences in plasma ammonia, free amino acid or fatty acid concentrations were apparent between the cortisol- and sham-treated groups. There was no change in hepatic glycogen content, whereas glutamine synthetase, allantoicase, arginase, aspartate aminotransferase, tyrosine aminotransferase, alanine aminotransferase, glutamate dehydrogenase, phosphoenolpyruvate carboxykinase and 3-hydroxyacyl-coenzyme A dehydrogenase activities were higher in the cortisol-treated fish liver compared with the sham-implanted fish. On the basis of these general increases in enzyme activities, our results suggest that cortisol stimulates nitrogen metabolism in the sea raven. Amino acid catabolism may be a major source of substrate for gluconeogenesis and/or oxidation, while fatty acid mobilization may provide the fuel for endogenous use by the liver in cortisol-treated sea raven. These results further support the hypothesis that cortisol plays a role in the regulation of glucose production in stressed fish.

Hepatic metabolism of genetically diabetic (db/db) mice. I. Carbohydrate metabolism

1975 ◽  
Vol 229 (6) ◽  
pp. 1702-1712 ◽  
Author(s):  
TM Chan ◽  
KM Young ◽  
NJ Hutson ◽  
FT Brumley ◽  
JH Exton
Keyword(s):  
Carbohydrate Metabolism ◽  
Glycogen Synthesis ◽  
Glucose Production ◽  
Hepatic Metabolism ◽  
Diabetic Mouse ◽  
Body Water ◽  
The Body ◽  
Genetically Diabetic Mice ◽  
Gluconeogenesis From Alanine

Hepatic carbohydrate metabolism in genetically diabetic mice (db/db) and their normal littermates has been studied. In db/db mice, body water was below normal and declined with age. The liver of db/db mice was abnormally large in relation to the metabolic mass of the body at all ages studied. In db/db mice, hepatic glycogenolysis, glycogen synthesis, glycogen synthetase, and phosphorylase were markedly increased. Gluconeogenesis from alanine or lactate in perfused livers of db/db mice was greater than normal per 100 g body water. Activities of fructose-1, 6-biophosphatase, glucose-6-phosphatase, glucokinase + hexokinase, and pyruvate kinase were elevated in livers of db/db mice. Diabetic mouse livers perfused with lactate showed a markedly reduced concentration of P-enolpyruvate and clear "forward crossover" between fructose-1, 6-P2 and fructose-6-P. In vivo glucose clearance, measured with [3-3H]glucose, in db/db mice was 170% that of normal mice. Data presented indicate that in livers of db/db mice: 1) glucose production is elevated prior to hyperglycemia, 2) glycogen turns over more rapidly, and 3) glycolytic and gluconeogenic enzymes are elevated paradoxically. These abnormalities are discussed from the viewpoint of their etiology.

Contribution of pancreatic hormone responses to the elevation in carbohydrate metabolism with reduced PaO2

1995 ◽  
Vol 268 (6) ◽  
pp. E1174-E1183
Author(s):  
B. A. Zinker ◽  
R. Wilson ◽  
D. H. Wasserman
Keyword(s):  
Carbohydrate Metabolism ◽  
Blood Lactate ◽  
Control Period ◽  
Glucose Production ◽  
Experimental Period ◽  
Insulin Levels ◽  
Arterial Blood ◽  
Glucagon And Insulin ◽  
Glucose Output ◽  
Pancreatic Hormone

Reduced O2 availability, as might occur under some physiological and pathological conditions, stimulates insulin and glucagon release and increases glucose fluxes and muscle carbohydrate metabolism. The aim of this study was to determine the role of reduced PO2, independent of changes in glucagon and insulin. In six dogs, in paired studies separated by 2 wk, glucagon and insulin levels were fixed throughout by infusion of somatostatin with basal intraportal glucagon and insulin replacement. A control period was followed by 90 min of breathing 21% (NO) or 8% (LO) O2. Isotopic and arteriovenous methods were used to assess carbohydrate metabolism. Measured variables were constant over time in NO. Arterial PO2 (Pao2) was approximately 100 mmHg in NO and approximately 30 mmHg in LO, resulting in a 50% fall in O2 content. Insulin, glucagon, and catecholamine levels were similar in NO and LO. Cortisol was significantly increased in LO. Arterial glucose was unchanged in both groups. In the last 45 min of the experimental period in LO, 1) glucose production (14 +/- 1 to 18 +/- 1 mumol.kg-1.min-1), glucose disappearance (15 +/- 1 to 17 +/- 1 mumol.kg-1.min-1), and net hepatic glucose output (11 +/- 1 to 15 +/- 1 mumol.kg-1.min-1) rose, 2) limb pyruvate oxidation (11 +/- 2 to 24 +/- 5 mumol/min) and estimated glycogenolysis (9 +/- 3 to 42 +/- 9 mumol/min) increased, 3) percentages of CO2 from limb pyruvate and glucose increased, and percentage of lactate from blood glucose decreased, and 4) arterial blood lactate was approximately 100% more, although net limb and hepatic lactate balances were unaltered, which suggests that neither liver nor muscle is the source of increased blood lactate. Comparison of these results with our previous study [Zinker et al. Am. J. Physiol. 266 (Endocrinol. Metab. 29): E921-E929, 1994] shows that the response to reduced PaO2, although present, is reduced when glucagon and insulin levels are fixed at basal. The majority of stimulation of glucose production by decreased PaO2 is still present when pancreatic hormones are clamped at basal, while the response by the hindlimb tissues is greatly reduced.

Effect of murine strain on metabolic pathways of glucose production after brief or prolonged fasting

2005 ◽  
Vol 289 (1) ◽  
pp. E53-E61 ◽  
Author(s):  
Shawn C. Burgess ◽  
F. Mark H. Jeffrey ◽  
Charles Storey ◽  
Angela Milde ◽  
Natasha Hausler ◽  
...  
Keyword(s):  
Genetic Manipulation ◽  
Glucose Production ◽  
Tca Cycle ◽  
Inbred Strains ◽  
Mouse Strains ◽  
Background Strain ◽  
Metabolic Fluxes ◽  
Inbred Strains Of Mice ◽  
Total Glucose

Background strain is known to influence the way a genetic manipulation affects mouse phenotypes. Despite data that demonstrate variations in the primary phenotype of basic inbred strains of mice, there is limited data available about specific metabolic fluxes in vivo that may be responsible for the differences in strain phenotypes. In this study, a simple stable isotope tracer/NMR spectroscopic protocol has been used to compare metabolic fluxes in ICR, FVB/N (FVB), C57BL/6J (B6), and 129S1/SvImJ (129) mouse strains. After a short-term fast in these mice, there were no detectable differences in the pathway fluxes that contribute to glucose synthesis. However, after a 24-h fast, B6 mice retain some residual glycogenolysis compared with other strains. FVB mice also had a 30% higher in vivo phospho enolpyruvate carboxykinase flux and total glucose production from the level of the TCA cycle compared with B6 and 129 strains, while total body glucose production in the 129 strain was ∼30% lower than in either FVB or B6 mice. These data indicate that there are inherent differences in several pathways involving glucose metabolism of inbred strains of mice that may contribute to a phenotype after genetic manipulation in these animals. The techniques used here are amenable to use as a secondary or tertiary tool for studying mouse models with disruptions of intermediary metabolism.

scholarly journals Markedly Diminished Lipolysis and Partial Restoration of Glucose Metabolism, without Changes in Fat Distribution after Extended Discontinuation of Protease Inhibitors in Severe Lipodystrophic Human Immunodeficient Virus-1-Infected Patients

2004 ◽  
Vol 89 (7) ◽  
pp. 3554-3560 ◽  
Author(s):  
Marc van der Valk ◽  
Gideon Allick ◽  
Gerrit Jan Weverling ◽  
Johannes A. Romijn ◽  
Mariette T. Ackermans ◽  
...  
Keyword(s):  
Glucose Production ◽  
Fat Distribution ◽  
Dual Energy ◽  
Glucose Disposal ◽  
Computed Tomography Scan ◽  
X Ray ◽  
Lipodystrophy Syndrome ◽  
Total Glucose ◽  
Tomography Scan ◽  
Hiv 1

Abstract Treatment for HIV-1 infection is often complicated by a lipodystrophy syndrome associated with insulin resistance and an elevated rate of lipolysis. In eight HIV-1 infected men with lipodystrophy syndrome, we studied the effects of replacement of protease inhibitor (PI) by abacavir on insulin sensitivity and lipolysis by hyperinsulinemic euglycemic clamp and on fat distribution assessed by dual-energy x-ray absorptiometry and computed tomography scan. Glucose metabolism and lipolysis were assessed by tracer dilution employing [6,6-2H2]glucose and [2H5]glycerol, respectively. Data are expressed as mean ± sd or 95% confidence interval (CI), as appropriate. There were no significant changes in fat distribution assessed by dual-energy x-ray absorptiometry and computed tomography scan at wk 36 and wk 96. The fasting total glucose production decreased from 16.1 ± 2.5 at study entry by 1.1 (range, −2.1 to −0.1) to 15.0 ± 1.5 μmol/kg·min after PI withdrawal at wk 36 (n = 8). In an analysis restricted to the patients on treatment at wk 96 (n = 6), the decrease was 0.9 (range, −2.1 to 0.3) μmol/kg·min. During insulin infusion, glucose oxidation (as percent of total glucose disposal) increased from 36.8 ± 12.7% by 11.0% (range, 1.3–20.8) to 47.9 ± 13.9% in the wk 36 analysis. In the analysis restricted to the patients on treatment at wk 96 (n = 6) the increase was 7.7 (−4.0 to 19.4)%. Fasting lipolysis decreased from 2.7 ± 0.6 μmol/kg·min by 0.9 (−1.6 to −0.2) to 1.8 ± 0.3 μmol/kg·min in the wk-96 analysis (n = 6). The replacement of the studied PIs by abacavir in severe lipodystrophic HIV-1-infected patients results in a marked reduction of lipolysis. In contrast, fasting glucose production and insulin-stimulated glucose oxidation improve moderately, whereas insulin-stimulated glucose disposal and fat distribution do not change.

scholarly journals Absorption and metabolism of glucose by the mesenteric-drained viscera of sheep fed on dried-grass or ground, maize-based diets

1985 ◽  
Vol 54 (2) ◽  
pp. 449-458 ◽  
Author(s):  
A. N. Janes ◽  
T. E. C. Weekes ◽  
D. G. Armstrong
Keyword(s):  
Small Intestine ◽  
Turnover Rate ◽  
Glucose Utilization ◽  
Venous Blood ◽  
Glucose Production ◽  
Glucose Absorption ◽  
Endogenous Glucose Production ◽  
Whole Body ◽  
Glucose Turnover ◽  
Total Glucose

1. Sheep fitted with re-entrant canulas in the proximal duodenum and terminal ileum were used to determine the amount of α-glucoside entering, and apparently disappearing from, the small intestine when either dried-grass or ground maize-based diets were fed. The fate of any α-glucoside entering the small intestine was studied by comparing the net disappearance of such a-glucoside from the small intestine with the absorption of glucose into the mesenteric venous blood.2. Glucose absorption from the small intestine was measured in sheep equipped with catheters in the mesenteric vein and carotid artery. A continuous infusion of [6-3H]glucose was used to determine glucose utilization by the mesenteric-drained viscera and the whole-body glucose turnover rate (GTR).3. The amounts of α-glucoside entering the small intestine when the dried-grass and maize-based diets were given were 13.9 (SE 1.5) and 95.4 (SE 16.2) g/24 h respectively; apparent digestibilities of such α-glucoside in the small intestine were 60 and 90% respectively.4. The net absorption of glucose into the mesenteric venous blood was —2.03 (SE 1.20) and 19.28 (SE 0.75) mmol/h for the dried-grass and maize-based diets respectively. Similarly, total glucose absorption amounted to 1.52 (SE 1.35) and 23.33 (SE 1.86) mmol/h (equivalent to 7 and 101 g/24 h respectively). These values represented 83 and 11 1% of the a-glucoside apparently disappearing from the small intestine, determined using the re-entrant cannulated sheep.5. Total glucose absorption represented 8 and 61% of the whole-body GTR for the dried-grass and maize-based diets respectively. Endogenous glucose production was significantly lower when the sheep were fed on the maize-based diet compared with the dried-grass diet.6. The mesenteric-drained viscera metabolized a small amount of glucose, equivalent to 234 and 17% of the total glucose absorbed for the dried-grass and maize-based diets respectively.7. It is concluded that a large proportion of the starch entering the small intestine of sheep given a maize-based diet is digested and absorbed as glucose, and thus contributes to the whole-body GTR.

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