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.

Effect of infusion of insulin into portal vein on hepatic extraction of insulin in anesthetized dogs

1975 ◽  
Vol 228 (5) ◽  
pp. 1580-1588 ◽  
Author(s):  
PE Harding ◽  
G Bloom ◽  
JB Field
Keyword(s):  
Portal Vein ◽  
Insulin Infusion ◽  
Significant Proportion ◽  
Fold Increase ◽  
Constant Infusion ◽  
Hepatic Extraction ◽  
Hepatic Glucose Output ◽  
Hepatic Glucose ◽  
Anesthetized Dogs ◽  
Glucose Output

Hepatic extraction of insulin was examined in anesthetized dogs before and after constant infusion of insulin (20 and 50 mU/min) with use of samples from the portal vein, mesenteric vein, left common hepatic vein, and the femoral artery. In 19 dogs, measurement of portal vein insulin concentration indicated an overall recovery of 110% of the insulin infused. The range varied from 9 to 303%, indicating the potential for serious error in sampling the portal vein. Equilibrium arterial insulin concentrations were achieved 20 min after starting the infusion. Prior to insulin infusion, hepatic extraction of insulin averaged 4.56 plus or minus 0.43 mUmin, representing an extraction coefficient of 0.42 of the insulin presented to the liver. The proportion of insulin extracted by the liver did not change significantly during insulin infusion despite a 10-fold increase in portal vein insulin concentrations. During the infusion of insulin, a significant proportion of the extraheptic clearance of insulin occurred in the mesenteric circulation. Infusion of insulin was associated with a significant increase in insulin extraction by tissues other than the liver and splanchnic beds. Initially, hepatic glucose output average 36 plus or minus 3 mg/min; by 20 min after insulin infusion, it was 16 plus or minus 5 mg/min. Despite continuation of insulin infusion, hepatic glucose output returned to control values even though arterial glucose concentration continued to fall. Hepatic glucose output increased with termination of insulin infusion.

scholarly journals Effect of insulin on glucose metabolism in the dog after portacaval transposition

1965 ◽  
Vol 209 (1) ◽  
pp. 221-226 ◽  
Author(s):  
Thomas E. Starzl ◽  
William A. Scanlan ◽  
Fred H. Thornton ◽  
Robert M. Wendel ◽  
Burton Stearn ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Insulin Infusion ◽  
Constant Infusion ◽  
Hepatic Glucose Output ◽  
Hepatic Glucose Metabolism ◽  
Catheter Technique ◽  
Significant Difference ◽  
Hepatic Glucose ◽  
Glucose Output ◽  
Portacaval Transposition

The effect of insulin on hepatic glucose metabolism was studied by a multiple-catheter technique in unanesthetized dogs with Eck fistula and with portacaval transposition. With the latter preparation, blood entering and leaving the liver was sampled from peripherally inserted catheters. In the unanesthetized Eck-fistula animals, insulin infusion produced a decrease in the hepatic glucose output. In the dogs with portacaval transposition, a constant infusion of insulin was given alternately by systemic and by intraportal routes. There was no significant difference between the effects of insulin administered by the two routes. During insulin infusion, glucose concentration differences across the liver were reduced, hepatic plasma flow was transiently elevated, and hepatic glucose output was decreased. After discontinuance of insulin, there was a transient rise of hepatic glucose output to above control values.

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.

Constant infusion and bolus injection of stable-label tracer give reproducible and comparable fasting HGO

1997 ◽  
Vol 273 (1) ◽  
pp. E192-E201 ◽  
Author(s):  
R. Hovorka ◽  
D. J. Eckland ◽  
D. Halliday ◽  
S. Lettis ◽  
C. E. Robinson ◽  
...  
Keyword(s):  
Steady State ◽  
Isotope Dilution ◽  
Coefficient Of Variation ◽  
Bolus Injection ◽  
Normal Subjects ◽  
Constant Infusion ◽  
Hepatic Glucose Output ◽  
Hepatic Glucose ◽  
Glucose Output

We have investigated the reproducibility of fasting hepatic glucose output (HGO) estimates by use of isotope dilution methodology of stable-label tracers. Six normal subjects were studied on two occasions 1 wk apart. After an overnight fast, the subjects received a bolus injection of 7 mg/kg of [U-13C]glucose and, simultaneously, a primed constant infusion of 0.05 mg.kg-1.min-1 of [6,6(-2)H]glucose. The bolus injection provided one estimate of HGO (HGOBOL), and the constant infusion provided two estimates of HGO, namely, HGO at 2 h (HGOINF2) and HGO at 4 h (HGOINF4), both with the assumption of steady-state conditions. All estimates were similar in value; HGOBOL was highest, followed by HGOINF2 and HGOINF4 [2.30 +/- 0.11 (SE), 2.17 +/- 0.12, and 2.01 +/- 0.13 mg.kg-1.min-1]. The constant infusion gave highly reproducible results. In the case of HGOINF2, the within-subject coefficient of variation (CV) was only 3% compared with 5% of HGOINF4. The reproducibility of HGOBOL was comparable with the within-subject CV of 7%. We conclude that a constant infusion and a bolus injection of stable-label tracer give reproducible and comparable estimates of HGO.

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.

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.

scholarly journals Hepatic and muscle insulin action during late pregnancy in the dog

2007 ◽  
Vol 292 (1) ◽  
pp. R447-R452 ◽  
Author(s):  
Cynthia C. Connolly ◽  
Tracy Papa ◽  
Marta S. Smith ◽  
D. Brooks Lacy ◽  
Phillip E. Williams ◽  
...  
Keyword(s):  
Insulin Infusion ◽  
Late Pregnancy ◽  
Hepatic Insulin Resistance ◽  
Hepatic Glucose Output ◽  
Hepatic Glucose ◽  
High Insulin ◽  
Skeletal Muscle Glucose Uptake ◽  
Glucose Output ◽  
Muscle Insulin Action ◽  
Arteriovenous Difference

We evaluated the effects of physiologic increases in insulin on hepatic and peripheral glucose metabolism in nonpregnant (NP) and pregnant (P; 3rd trimester) conscious dogs ( n = 9 each) using tracer and arteriovenous difference techniques during a hyperinsulinemic euglycemic clamp. Insulin was initially (−150 to 0 min) infused intraportally at a basal rate. During 0–120 min (Low Insulin), the rate was increased by 0.2 mU·kg−1·min−1, and from 120 to 240 min (High Insulin) insulin was infused at 1.5 mU·kg−1·min−1. Insulin concentrations were significantly higher in NP than P during all periods. Matched subsets ( n = 5 NP and 6 P) were identified. In the subsets, insulin was 7 ± 1, 9 ± 1, and 28 ± 3 μU/ml (basal, Low Insulin, and High Insulin, respectively) in NP, and 5 ± 1, 7 ± 1, and 27 ± 3 μU/ml in P. Net hepatic glucose output was suppressed similarly in both subsets (≥50% with Low Insulin, 100% with High Insulin), as was endogenous glucose rate of appearance. During High Insulin, NP dogs required more glucose (10.8 ± 1.5 vs. 6.2 ± 1.0 mg·kg−1·min−1, P < 0.05), and hindlimb (primarily skeletal muscle) glucose uptake tended to be greater in NP than P (18.6 ± 2.5 mg/min vs. 13.6 ± 2.0 mg/min, P = 0.06). The normal canine liver remains insulin sensitive during late pregnancy. Differing insulin concentrations in pregnant and nonpregnant women and excessive insulin infusion rates may explain previous findings of hepatic insulin resistance in healthy pregnant women.

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