Prior exercise and the response to insulin-induced hypoglycemia in the dog

2002 ◽  
Vol 282 (5) ◽  
pp. E1128-E1138 ◽  
Author(s):  
Yoshiharu Koyama ◽  
Pietro Galassetti ◽  
Robert H. Coker ◽  
R. Richard Pencek ◽  
D. Brooks Lacy ◽  
...  
Keyword(s):  
Portal Vein ◽  
Insulin Action ◽  
Treadmill Exercise ◽  
Primary Site ◽  
Moderate Exercise ◽  
Hepatic Glucose Output ◽  
Prior Exercise ◽  
Hepatic Glucose ◽  
Glucose Output ◽  
Hepatic Glucose Uptake

To test whether hepatic insulin action and the response to an insulin-induced decrement in blood glucose are enhanced in the immediate postexercise state as they are during exercise, dogs had sampling (artery, portal vein, and hepatic vein) catheters and flow probes (portal vein and hepatic artery) implanted 16 days before a study. After 150 min of moderate treadmill exercise or rest, dogs were studied during a 150-min hyperinsulinemic (1 mU · kg−1· min−1) euglycemic ( n = 5 exercised and n = 9 sedentary) or hypoglycemic (65 mg/dl; n = 8 exercised and n = 9 sedentary) clamp. Net hepatic glucose output (NHGO) and endogenous glucose appearance (Ra) and utilization (Rd) were assessed with arteriovenous and isotopic ([3-3H]glucose) methods. Results show that, immediately after prolonged, moderate exercise, in relation to sedentary controls: 1) the glucose infusion rate required to maintain euglycemia, but not hypoglycemia, was higher; 2) Rdwas greater under euglycemic, but not hypoglycemic conditions; 3) NHGO, but not Ra, was suppressed more by a hyperinsulinemic euglycemic clamp, suggesting that hepatic glucose uptake was increased; 4) a decrement in glucose completely reversed the enhanced suppression of NHGO by insulin that followed exercise; and 5) arterial glucagon and cortisol were transiently higher in the presence of a decrement in glucose. In summary, an increase in insulin action that was readily evident under euglycemic conditions after exercise was abolished by moderate hypoglycemia. The means by which the glucoregulatory system is able to overcome the increase in insulin action during moderate hypoglycemia is related not to an increase in Rabut to a reduction in insulin-stimulated Rd. The primary site of this reduction is the liver.

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.

Insulin as a mediator of hepatic glucose uptake in the conscious dog

1982 ◽  
Vol 242 (2) ◽  
pp. E97-E101 ◽  
Author(s):  
A. D. Cherrington ◽  
P. E. Williams ◽  
N. Abou-Mourad ◽  
W. W. Lacy ◽  
K. E. Steiner ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Plasma Insulin ◽  
Marked Effect ◽  
Glucose Infusion ◽  
Hepatic Glucose Output ◽  
Intravenous Glucose ◽  
Conscious Dog ◽  
Hepatic Glucose ◽  
Glucose Output ◽  
Hepatic Glucose Uptake

The aim of this study was to determine whether a physiological increment in plasma insulin could promote substantial hepatic glucose uptake in response to hyperglycemia brought about by intravenous glucose infusion in the conscious dog. To accomplish this, the plasma glucose level was doubled by glucose infusion into 36-h fasted dogs maintained on somatostatin, basal glucagon, and basal or elevated intraportal insulin infusions. In the group with basal glucagon levels and modest hyperinsulinemia (33 +/- 2 micro U/ml), the acute induction of hyperglycemia (mean increment of 120 mg/dl) caused marked net hepatic glucose uptake (3.7 +/- 0.5 mg . kg-1 . min-1). In contrast, similar hyperglycemia brought about in the presence of basal glucagon and basal insulin levels described net hepatic glucose output in 56%, but did not cause net hepatic glucose uptake. The length of fast was not crucial to the response because similar signals (insulin, 38 +/- 6 micro U/ml; glucose increment, 127 mg/dl) promoted identical net hepatic glucose uptake (3.8 +/- 0.6 mg . kg-1 . min-1) in dogs fasted for only 16 h. In conclusion, in the conscious dog, a) physiologic increments in plasma insulin have a marked effect on the ability of hyperglycemia to stimulate net hepatic glucose uptake, and b) it is not necessary to administer glucose orally to promote substantial net hepatic glucose uptake.

Prior exercise increases net hepatic glucose uptake during a glucose load

1999 ◽  
Vol 276 (6) ◽  
pp. E1022-E1029 ◽  
Author(s):  
Pietro Galassetti ◽  
Robert H. Coker ◽  
Drury B. Lacy ◽  
Alan D. Cherrington ◽  
David H. Wasserman
Keyword(s):  
Portal Vein ◽  
Glucose Uptake ◽  
Control Period ◽  
Vena Cava ◽  
Experimental Period ◽  
Glucose Infusion ◽  
Glucose Load ◽  
Prior Exercise ◽  
Hepatic Glucose ◽  
Hepatic Glucose Uptake

The aim of these studies was to determine whether prior exercise enhances net hepatic glucose uptake (NHGU) during a glucose load. Sampling catheters (carotid artery, portal, hepatic, and iliac veins), infusion catheters (portal vein and vena cava), and Doppler flow probes (portal vein, hepatic and iliac arteries) were implanted. Exercise (150 min; n = 6) or rest ( n = 6) was followed by a 30-min control period and a 100-min experimental period (3.5 mg ⋅ kg−1⋅ min−1of glucose in portal vein and as needed in vena cava to clamp arterial blood glucose at ∼130 mg/dl). Somatostatin was infused, and insulin and glucagon were replaced intraportally at fourfold basal and basal rates, respectively. During experimental period the arterial-portal venous (a-pv) glucose gradient (mg/dl) was −18 ± 1 in sedentary and −19 ± 1 in exercised dogs. Arterial insulin and glucagon were similar in the two groups. Net hepatic glucose balance (mg ⋅ kg−1⋅ min−1) shifted from 1.9 ± 0.2 in control period to −1.8 ± 0.2 (negative rates represent net uptake) during experimental period in sedentary dogs (Δ3.7 ± 0.5); with prior exercise it shifted from 4.1 ± 0.3 ( P < 0.01 vs. sedentary) in control period to −3.2 ± 0.4 ( P < 0.05 vs. sedentary) during experimental period (Δ7.3 ± 0.7, P < 0.01 vs. sedentary). Net hindlimb glucose uptake (mg/min) was 4 ± 1 in sedentary animals in control period and 13 ± 2 during experimental period; in exercised animals it was 7 ± 1 in control period ( P < 0.01 vs. sedentary) and 32 ± 4 ( P < 0.01 vs. sedentary) during experimental period. As the total glucose infusion rate (mg ⋅ kg−1⋅ min−1) was 7 ± 1 in sedentary and 11 ± 1 in exercised dogs, ∼30% of the added glucose infusion due to prior exercise could be accounted for by the greater NHGU. In conclusion, when determinants of hepatic glucose uptake (insulin, glucagon, a-pv glucose gradient, glycemia) are controlled, prior exercise increases NHGU during a glucose load due to an effect that is intrinsic to the liver. Increased glucose disposal in the postexercise state is therefore due to an improved ability of both liver and muscle to take up glucose.

Preserved direct hepatic insulin action in rats with diet-induced hepatic steatosis

2004 ◽  
Vol 286 (5) ◽  
pp. E828-E833 ◽  
Author(s):  
Roland Buettner ◽  
Iris Ottinger ◽  
Jürgen Schölmerich ◽  
L. Cornelius Bollheimer
Keyword(s):  
Insulin Sensitivity ◽  
Hepatic Steatosis ◽  
Insulin Action ◽  
Glycogen Synthase ◽  
Hepatic Glucose Output ◽  
Hepatic Insulin Sensitivity ◽  
Significant Difference ◽  
Hepatic Glucose ◽  
Glucose Output

Recent in vivo studies have demonstrated a strong negative correlation between liver triglyceride content and hepatic insulin sensitivity, but a causal relationship remains to be established. We therefore have examined parameters of direct hepatic insulin action on isolated steatotic livers from high-fat (HF)-fed rats compared with standard chow (SC)-fed controls. Direct hepatic action of insulin was assayed in Wistar rats after 6 wk of HF diet by measuring the insulin-induced suppression of epinephrine-induced hepatic glucose output in an isolated liver perfusion system. Insulin-induced activation of glycogen synthase was measured by quantifying the incorporation of radioactive UDP-glucose into glycogen in HF and SC liver lysates. HF diet induced visceral obesity, mild insulin resistance, and hepatic steatosis. Both suppression of epinephrine-induced glycogenolysis and activation of glycogen synthase by insulin were sustained in HF rats; no significant difference from SC controls could be detected. In conclusion , in our model, triglyceride accumulation into the liver was not sufficient to impair direct hepatic insulin action. The data argue for an important role of systemic factors in the regulation of hepatic glucose output and hepatic insulin sensitivity in vivo.

scholarly journals The Importance of the Mechanisms by which Insulin Regulates Meal-Associated Liver Glucose Uptake in the Dog

2021 ◽  
Author(s):  
Guillaume Kraft ◽  
Katie C. Coate ◽  
Marta Smith ◽  
Ben Farmer ◽  
Melanie Scott ◽  
...  
Keyword(s):  
Portal Vein ◽  
Glucose Uptake ◽  
Insulin Action ◽  
Insulin Infusion ◽  
Insulin Receptors ◽  
Postprandial Glucose ◽  
Maximal Stimulation ◽  
Hepatic Glucose ◽  
Healthy Dogs ◽  
Hepatic Glucose Uptake

Hepatic glucose uptake (HGU) is critical for maintaining normal postprandial glucose metabolism. Insulin is clearly a key regulator of HGU, but the physiologic mechanisms by which it acts have yet to be established. This study sought to determine the mechanisms by which insulin regulates liver glucose uptake under postprandial-like conditions (hyperinsulinemia, hyperglycemia, and a positive portal vein to arterial glucose gradient). Portal vein insulin infusion increased hepatic insulin levels 5-fold in healthy dogs. In one group (n=7), the physiologic response was allowed to fully occur, while in another (n=7), insulin’s indirect hepatic effects, occurring secondary to its actions on adipose tissue, pancreas, and brain, were blocked. This was accomplished by infusing triglyceride (intravenous), glucagon (portal vein), and inhibitors of brain insulin action (intracerebroventricular) to prevent decreases in plasma free fatty acids or glucagon, while blocking increased hypothalamic insulin signaling for 4h. In contrast to the indirect hepatic effects of insulin, which were previously shown capable of independently generating a half-maximal stimulation of HGU, direct hepatic insulin action was by itself able to fully stimulate HGU. This suggests that under hyperinsulinemic/hyperglycemic conditions insulin’s indirect effects are redundant to direct engagement of hepatocyte insulin receptors.

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.

Hepatic insulin and glucagon extraction after their augmented secretion in dogs.

1978 ◽  
Vol 235 (1) ◽  
pp. E88
Author(s):  
S Röjdmark ◽  
G Bloom ◽  
M C Chou ◽  
J B Jaspan ◽  
J B Field
Keyword(s):  
Portal Vein ◽  
Molecular Heterogeneity ◽  
Hepatic Extraction ◽  
Hepatic Glucose Output ◽  
Antagonistic Effects ◽  
Molar Ratios ◽  
Control Value ◽  
Hepatic Glucose ◽  
Anesthetized Dogs ◽  
Glucose Output

Effects of intravenous arginine and cholecystokinin-pancreozymin (CCK-PZ) infusion on hepatic extraction of insulin (EI) and glucagon (EGG) and also on hepatic glucose output (HGO) were studied in anesthetized dogs. Because insulin and glucagon exert antagonistic effects on HGO, insulin:glucagon (I/GG) molar ratios were determined in the portal vein and also in peripheral vessels. During the arginine-CCK-PZ infusion the amount of insulin and glucagon coming to the liver increased 12- and 15-fold, respectively. In contrast EI decreased significantly from a control value of 62 +/- 6% to a nadir of 22 +/- 13%. EGG (control value 19 +/- 9%), however, was unaffected by arginine-CCK-PZ. The absence of any alteration in EGG cannot be attributed to the molecular heterogeneity of the immunoreactive glucagon. HGO increased fourfold in response to the pancreatic stimulation, whereas portal I/GG decreased significantly from 8.2 +/- 0.9 to 5.0 +/- 0.7. The concurrent femoral arterial I/GG (control 3.7 +/- 1.0) and mesenteric venous I/GG (control 2.1 +/- 0.5) increased significantly. These observations indicate that portal, but not peripheral, I/GG measurements reflect hepatic events in anesthetized dogs, probably because of the different extraction patterns for insulin and glucagon.

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