Does a glucose load inhibit hepatic sugar output? C14 glucose studies in eviscerated dogs

1959 ◽  
Vol 197 (1) ◽  
pp. 60-62 ◽  
Author(s):  
Robert Steele ◽  
Jonathan S. Bishop ◽  
Rachmiel Levine
Keyword(s):  
Plasma Glucose ◽  
Glucose Concentration ◽  
Alternative Explanation ◽  
Specific Activity ◽  
The Body ◽  
Glucose Load ◽  
Hepatic Glucose Output ◽  
Minute Amount ◽  
Hepatic Glucose ◽  
Glucose Output

A sequence of changes in plasma glucose specific activity is observed in intact dogs when a large amount of C12 glucose is injected intravenously following the tagging of the circulating glucose by injection of a minute amount of C14 glucose. Similar changes are observed when the same procedure is applied to eviscerated dogs in which the plasma glucose concentration is being maintained by a continuous infusion of C12 glucose, this infusion being continued unchanged after the C12 glucose load is given. These results show that inhibition of hepatic glucose output is not the only or the necessary explanation for the cessation in the exponential fall of plasma glucose specific activity which is seen in the intact dog following an intravenous C12 glucose load. An alternative explanation of the effect is offered which is based on the slowness of mixing of the injected C12 glucose load with a part of the body glucose pool.

Effect of phlorizin on hepatic glucose output

1962 ◽  
Vol 202 (1) ◽  
pp. 149-154 ◽  
Author(s):  
Edwin H. Kolodny ◽  
Robert Kline ◽  
Norman Altszuler
Keyword(s):  
Plasma Glucose ◽  
Vena Cava ◽  
The Body ◽  
Hepatic Veins ◽  
Hepatic Glucose Output ◽  
Direct Stimulation ◽  
Indwelling Catheters ◽  
Glucose Levels ◽  
Hepatic Glucose ◽  
Glucose Output

Using phlorizin as an experimental tool, an investigation of the mechanisms responsible for the maintenance of plasma glucose levels was undertaken. Infusion of phlorizin has been shown to produce a prompt glucosuria and increase in hepatic glucose output (HGO), but without discernable hypoglycemia. This raises the question as to the nature of the stimulus for the increased HGO. The effect of phlorizin on net HGO was studied in anesthetized dogs with indwelling catheters in the portal and hepatic veins. Infusion of phlorizin into normal dogs produced a prompt glucosuria and a concomitant increase in HGO, without significant changes in the plasma glucose concentration in the portal vein. In functionally nephrectomized dogs, phlorizin did not change HGO nor circulating glucose levels. In dogs with intact kidneys, when glucosuria was prevented by urine recirculation into the inferior vena cava, the infusion of phlorizin again failed to alter HGO or circulating glucose levels. The data indicate that the phlorizin-induced increase in HGO is dependent on loss of glucose from the body. The enhancement of HGO could not be ascribed to a direct stimulation of the liver, kidney, or endocrine glands, or to an impairment of glucose utilization. Possible mechanisms to explain this effect of phlorizin are discussed.

Estimation of Hepatic Glucose Output in Non-Steady State. The Simultaneous Use of 2-3H-glucose and 14C-glucose in the Dog

1974 ◽  
Vol 52 (2) ◽  
pp. 215-224 ◽  
Author(s):  
Thomas B. Issekutz ◽  
Bela Issekutz Jr. ◽  
Dariush Elahi
Keyword(s):  
Steady State ◽  
Specific Activity ◽  
Base Line ◽  
Glucose Load ◽  
Hepatic Glucose Output ◽  
Constant Rate ◽  
Hepatic Glucose ◽  
Glucose Output ◽  
Infusion Technique ◽  
Single Exponential Function

The rate of appearance of glucose (Ra) was estimated in a non-steady state caused by the infusion of glucose (exogenous increase of Ra) or glucagon (increase of hepatic glucose output) in unanesthetized dogs with indwelling arterial and venous catheters. First, Ra was measured with 2-3H-glucose according to the primed constant rate infusion technique in steady state, then with the onset of the perturbation the infusion of a second tracer, (U) 14C-glucose, was started. Exponential functions were fitted to the two specific activity curves. The second tracer made it possible to calculate Ra during the non-steady state without the need to assume a definite value for the "miscible" glucose space (V). The latter could also be calculated and it proved to be a single exponential function of time elapsed from the start of the perturbation. In the first few minutes the glucose load (10 or 15 mg/kg min for 120 min) caused a sharp fall of hepatic glucose output. This was followed by a rise of various degrees before the endogenous glucose output reached the steady state at about 50 or 70% below the base-line values. During the glucose load, in steady state (U) 14C-glucose as a tracer gave about 10% lower values for Ra than tritiated glucose.

scholarly journals Measurement of Hepatic Glucose Output, Krebs Cycle, and Gluconeogenic Fluxes by NMR Analysis of a Single Plasma Glucose Sample

1998 ◽  
Vol 263 (1) ◽  
pp. 39-45 ◽  
Author(s):  
John G. Jones ◽  
Rui A. Carvalho ◽  
Byron Franco ◽  
A.Dean Sherry ◽  
Craig R. Malloy
Keyword(s):  
Plasma Glucose ◽  
Krebs Cycle ◽  
Nmr Analysis ◽  
Hepatic Glucose Output ◽  
Hepatic Glucose ◽  
Glucose Output ◽  
Single Plasma

Influence of somatostatin on glucagon- and epinephrine-stimulated hepatic glucose output in the dog.

1979 ◽  
Vol 236 (2) ◽  
pp. E113
Author(s):  
L Saccà ◽  
R Sherwin ◽  
P Felig
Keyword(s):  
Plasma Glucose ◽  
Glucose Production ◽  
Conscious Dogs ◽  
Insulin Deficiency ◽  
Hepatic Glucose Output ◽  
Glucose Kinetics ◽  
Insulin Levels ◽  
Hepatic Glucose ◽  
Glucose Output ◽  
Insulin Replacement

Glucose kinetics were measured using [3-3H]glucose in conscious dogs during the infusion of: 1) glucagon alone; 2) glucagon plus somatostatin with insulin replacement; 3) epinephrine alone; and 4) epinephrine plus somatostatin with insulin and glucagon replacement. Infusion of glucagon alone resulted in a 10-15 mg/dl rise in plasma glucose and a transient 45% rise in glucose production. When somatostatin and insulin were added, a four- to fivefold greater rise in plasma glucose and glucose production was observed. Glucagon levels were comparable to those achieved with infusion of glucagon alone, whereas peripheral insulin levels increased three- to fourfold above baseline, suggesting adequate replacement of preinfusion portal insulin levels. Infusion of epinephrine alone produced a 40% rise in plasma glucose and a 100% rise in glucose production. When somatostatin, insulin, and glucagon were added to epinephrine, the rise in glucose production was reduced in 65% despite replacement of glucagon levels and presumably mild portal insulin deficiency. These findings suggest that somatostatin: 1) potentiates the stimulatory effect of physiologic hyperglucagonemia on glucose production independent of insulin availability and 2) blunts the stimulatory effect of physiologic increments of epinephrine independent of glucagon availability.

Regulation of hepatic glucose output during exercise by circulating glucose and insulin in humans

1986 ◽  
Vol 250 (3) ◽  
pp. R411-R417 ◽  
Author(s):  
A. B. Jenkins ◽  
S. M. Furler ◽  
D. J. Chisholm ◽  
E. W. Kraegen
Keyword(s):  
Plasma Glucose ◽  
Insulin Infusion ◽  
Cycle Ergometer ◽  
Constant Infusion ◽  
Hepatic Glucose Output ◽  
Fixed Rate ◽  
Ergometer Exercise ◽  
Hepatic Glucose ◽  
Glucose Output ◽  
Simple Difference

We have tested the hypothesis that hepatic glucose output (Ra) during exercise in humans is subject to feedback control by circulating glucose within a control range that is determined by the circulating insulin concentration. Three exercise protocols based on 60-min cycle ergometer exercise at 55% maximal O2 consumption were used: 1) control, 2) insulin infusion with a euglycemic clamp, and 3) insulin infusion with a fixed-rate glucose infusion. Ra was measured using a constant infusion of [3H]glucose. During the glucose clamp there was no Ra response to exercise. There were significant inverse relationships between Ra and plasma glucose during control exercise (r = -0.73, P less than 0.001) and exercise with fixed-rate glucose and insulin infusion (r = -0.96, P less than 0.001). During the fixed-rate glucose and insulin infusion, plasma glucose fell from the commencement of exercise but stabilized at a lower level. These results are interpreted in terms of a simple difference controller where Ra is proportional to the deviation of plasma glucose from a defined set point. Insulin affects Ra and regulates the steady-state glucose level by altering the sensitivity of this control system.

Selective insulinization of liver in conscious diabetic dogs

1985 ◽  
Vol 249 (2) ◽  
pp. E152-E159
Author(s):  
R. S. Spangler
Keyword(s):  
Steady State ◽  
Glucose Utilization ◽  
Dose Range ◽  
Lipid Vesicles ◽  
Glucose Load ◽  
Hepatic Glucose Output ◽  
Hepatic Glucose ◽  
Diabetic Dogs ◽  
Glucose Output ◽  
Hepatic Glucose Uptake

Insulin encapsulated in lipid vesicles and targeted to hepatocytes by means of a digalactosyl diglyceride moiety [(designated vesicle encapsulated insulin (VEI)] was administered intravenously to conscious catheterized diabetic dogs to determine the effects of hepatic and extrahepatic glucose utilization. Our results indicate that VEI administered intravenously to diabetic dogs over a dose range of 0.5 to 2.0 mU X kg-1 X min-1 reduces hepatic glucose output or induces hepatic glucose uptake without causing any significant alteration in the rate of extrahepatic glucose utilization. Steady-state comparisons of 1.0 mU X kg-1 X min-1 VEI with intraportal and peripherally administered insulin revealed that VEI and intraportal insulin result in significantly less extrahepatic glucose utilization than does an equivalent dose of peripherally administered insulin (6.36 +/- 1.21 and 5.08 +/- 0.97 vs. 8.82 +/- 1.61 mg X kg-1 X min-1; P less than 0.03). Through the use of VEI, we were able to significantly alter the deposition of intravenously administered glucose from 11% hepatic and 89% extrahepatic noted with peripheral insulin to 35% hepatic and 65% extrahepatic with VEI (P less than 0.03). Thus, by encapsulating insulin into a lipid carrier specifically targeted to the liver, selective hepatic insulinization can be achieved. As a result of this approach, one can alter the distribution of a glucose load to favor hepatic deposition.

Measurement of hepatic glucose output and hepatic blood flow in response to glucagon

1959 ◽  
Vol 196 (2) ◽  
pp. 315-318 ◽  
Author(s):  
William C. Shoemaker ◽  
Theodore B. Van Itallie ◽  
William F. Walker
Keyword(s):  
Blood Flow ◽  
Hepatic Blood Flow ◽  
Glucose Concentration ◽  
Base Line ◽  
Hepatic Glucose Output ◽  
Marked Rise ◽  
Hepatic Glucose ◽  
The Mean ◽  
Glucose Output ◽  
Venous Glucose

Arterial, portal and hepatic venous glucose concentrations and hepatic blood flow were simultaneously measured in nine dogs in the postabsorptive state, and after intravenous administration of glucagon. A marked rise in hepatic venous glucose concentration occurred promptly after glucagon administration. This rise coincided with a mean increase in estimated hepatic blood flow of approximately 100%. This increase in hepatic blood flow following the administration of glucagon was regularly observed in all animals; the increase in blood flow ranged from 41 to 204% in this series. Hepatic glucose output was calculated by multiplying the portal-hepatic vein gradient by the hepatic blood flow. The mean hepatic glucose output of the series increased from base line of 73 mg/min. to a maximum of 381 mg/min. in response to glucagon.

Plasma glucose and insulin responses to oral and intravenous glucose in cold-exposed humans

1988 ◽  
Vol 65 (6) ◽  
pp. 2395-2399 ◽  
Author(s):  
A. L. Vallerand ◽  
J. Frim ◽  
M. F. Kavanagh
Keyword(s):  
Glucose Tolerance ◽  
Glucose Uptake ◽  
Carbohydrate Metabolism ◽  
Cold Exposure ◽  
Plasma Glucose ◽  
Hepatic Glucose Output ◽  
Hepatic Glucose ◽  
Oral Gtt ◽  
Glucose Output ◽  
Insulin Responses

Although glucose tolerance and skeletal muscle glucose uptake are markedly improved by cold exposure in animals, little is known about such responses in humans. This study used two variations of a glucose tolerance test (GTT) to investigate changes in carbohydrate metabolism in healthy males during nude exposure to cold. In experiment 1, an oral GTT was performed in the cold and in the warm (3 h at 10 or 29 degrees C). To bypass the gastrointestinal tract, and to suppress hepatic glucose output, a second experiment was carried out as described above, using an intravenous GTT. Even though cold exposure raised metabolic rate greater than 2.5 times, plasma glucose and insulin responses to an oral GTT remained unaltered. In contrast, cold exposure reduced the entire plasma glucose profile as a function of time during the intravenous GTT (P less than 0.05), as plasma glucose was returned to basal levels within 1 h in comparison to a full 2 h in the warm, despite low insulin levels. The results of the intravenous GTT demonstrate that even with low insulin levels, carbohydrate metabolism is increased in cold-exposed males. This effect could be masked in the oral GTT by gastrointestinal factors and a high hepatic glucose output. Cold exposure may enhance insulin sensitivity and/or responsiveness for glucose uptake, mainly in shivering skeletal muscles.

Mechanisms of postabsorptive hyperglycemia in streptozotocin diabetic rats

1996 ◽  
Vol 270 (5) ◽  
pp. E752-E758 ◽  
Author(s):  
J. K. Wi ◽  
J. K. Kim ◽  
J. H. Youn
Keyword(s):  
Glucose Uptake ◽  
Plasma Glucose ◽  
Diabetic Rats ◽  
Normal Rate ◽  
Hepatic Glucose Output ◽  
Hepatic Glucose ◽  
Glucose Clearance ◽  
Streptozotocin Diabetic Rats ◽  
Acute Changes ◽  
Glucose Output

Postabsorptive hepatic glucose output (HGO) was estimated in normal (n = 9) and streptozotocin (STZ) diabetic rats after a 6-h [3-3H]glucose infusion. In diabetic rats, HGO was estimated at ambient (n = 12) or normal (achieved via phlorizin infusion; n = 9) glucose concentrations. HGO was not statistically different between normal and diabetic rats (63 +/- 3 vs. 77 +/- 10 mumol.kg-1.min-1; P> 0.05). HGO was also normal in diabetic rats even when plasma glucose was normalized with phlorizin infusion (71 +/- 5 vs. 63 +/- 3 mumol.kg-1.min-1; P> 0.05). In contrast, peripheral glucose uptake, when estimated at matched euglycemia, was lower by approximately 25% in diabetic than in normal rate (46 +/- 6 vs. 62 +/- 3 mumol.kg-1.min-1; P < 0.01). In addition, acute changes in plasma glucose concentrations did not have significant effects on HGO or peripheral glucose uptake in diabetic rats (P> 0.05), resulting in markedly decreased glucose clearance at ambient hyperglycemia (P < 0.001). In conclusion, postabsorptive HGO was not elevated in a majority (17 of 21) of STZ diabetic rats with severe hyperglycemia and therefore was not responsible for postabsorptive hyperglycemia. Our data suggest that an impairment in the ability of glucose to regulate peripheral glucose uptake or HGO develops in STZ diabetes and contributes to postabsorptive hyperglycemia.

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