Hepatic and Peripheral Insulin Action in Chronic Renal Failure before and during Continuous Ambulatory Peritoneal Dialysis

1989 ◽  
Vol 77 (4) ◽  
pp. 383-388 ◽  
Author(s):  
A. Heaton ◽  
R. Taylor ◽  
D. G. Johnston ◽  
M. K. Ward ◽  
R. Wilkinson ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Infusion Rate ◽  
Insulin Action ◽  
Insulin Infusion ◽  
Glucose Turnover ◽  
Insulin Infusion Rate ◽  
Hepatic Glucose ◽  
Total Glucose ◽  
Glucose Output

1. A three-step hyperinsulinaemic euglycaemic clamp was performed in six uraemic patients before dialysis and after 3 months of treatment with continuous ambulatory peritoneal dialysis, and in seven matched normal control subjects. Glucose turnover was assessed basally and during the clamp using [3-3H]glucose as a tracer. 2. The glucose infusion rate required to maintain euglycaemia was insignificantly higher in normal subjects compared with undialysed uraemic subjects at each insulin infusion rate. 3. The isotopically assessed total glucose turnover was also similar in normal and uraemic subjects. Basal hepatic glucose output was again similar in uraemic and control subjects and output was suppressed to a similar degree at each insulin infusion rate. 4. After treatment with continuous ambulatory peritoneal dialysis, the glucose infusion rate and the total glucose turnover during the clamp rose significantly at all three insulin concentrations (P < 0.05), but remained insignificantly different from normal control values. Hepatic glucose output was unchanged. 5. Peripheral insulin action was improved during continuous ambulatory peritoneal dialysis, but hepatic insulin action was unchanged.

Changes in insulin action and GLUT-4 with 6 days of inactivity in endurance runners

1996 ◽  
Vol 80 (1) ◽  
pp. 240-244 ◽  
Author(s):  
M. D. Vukovich ◽  
P. J. Arciero ◽  
W. M. Kohrt ◽  
S. B. Racette ◽  
P. A. Hansen ◽  
...  
Keyword(s):  
Infusion Rate ◽  
Insulin Action ◽  
Insulin Infusion ◽  
Glucose Disposal ◽  
Inactive State ◽  
Transporter Protein ◽  
Glut 4 ◽  
Insulin Infusion Rate ◽  
Endurance Runners ◽  
Trained Runners

The purpose of this investigation was to determine whether decreased insulin action after 6 days of inactivity in endurance-trained runners was associated with a decrease in skeletal muscle glucose transporter protein levels (GLUT-4) in the gastrocnemius muscle. Seven endurance runners (5 men and 2 women) volunteered to participate in this investigation. All subjects had normal glucose tolerance as determined by the National Diabetes Data Group guidelines. Each individual completed two hyperinsulinemic euglycemic clamps at insulin infusion rates of 15 (LO) and 40 (HI) mU.m-2.min-1, one approximately 18 h after a training bout and the second after 6 days of inactivity (IA). Muscle biopsies for the measurement of GLUT-4 were obtained from the gastrocnemius before each clamp. Glucose disposal rates during the last 30 min of each insulin infusion were significantly reduced after 6 days of IA, averaging 6.45 +/- 1.04 mg.kg fat-free mass (FFM)-1.min-1 before and 4.55 +/- 0.56 mg.kg FFM-1.min-1 after detraining for the LO insulin infusion rate and 13.77 +/- 0.88 mg.kg FFM-1.min-1 before and 11.81 +/- 0.60 mg.kg FFM-1.min-1 after detraining for the HI insulin infusion rate (both P < 0.05), despite the fact that plasma insulin was higher in the inactive state (LO, 19.2 +/- 0.9 microU/ml before and 23.4 +/- 1.5 microU/ml after detraining; HI, 56.0 +/- 2.0 microU/ml before and 61.6 +/- 1.6 microU/ml after detraining; P < 0.05)). Calculated insulin clearance was greater in the trained than in the inactive state (P < 0.03). Muscle GLUT-4 transporter protein after 6 days of IA was reduced by 17.5 +/- 5.4% (P < 0.02). These results demonstrate that 6 days of IA reduces insulin action in endurance-trained runners and suggest that a reduction in muscle GLUT-4 transporter level plays a role in the decrease in glucose disposal rates.

Effect of intraportal and peripheral insulin on glucose turnover and recycling in diabetic dogs

1983 ◽  
Vol 244 (2) ◽  
pp. E190-E195 ◽  
Author(s):  
R. W. Stevenson ◽  
J. A. Parsons ◽  
K. G. Alberti
Keyword(s):  
Insulin Infusion ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Glucose Turnover ◽  
Hepatic Glucose Output ◽  
Normal Range ◽  
Hepatic Glucose ◽  
Diabetic Dogs ◽  
Glucose Output ◽  
Glucose Recycling

The effects of peripheral and portal intravenous infusions of insulin on hepatic glucose production and glucose recycling have been compared in conscious diabetic dogs. Glucose turnover (Ra) was estimated using a priming dose of [3-3H]glucose and [1-14C]-glucose followed by constant intravenous infusion. Glucose recycling was calculated from 3H-Ra - 14C-Ra. In eight normal dogs, mean 3H-Ra was 3.0 mg X kg-1 X min-1 and recycling 19%. When these dogs were made diabetic with alloxan and streptozotocin the 3H-Ra rose to 6.2 mg X kg-1 X min-1 (P less than 0.001) and recycling to 24% (P less than 0.05). Insulin infusion for 2.5 h at 0.006 U X kg-1 X h-1 intraportally decreased 3H-Ra to 4.0 mg X kg-1 X min-1 (P less than 0.01 compared with untreated diabetic), whereas peripheral infusion at this rate had no significant effect. Insulin infusion at 0.05 U X kg-1 X h-1 by the peripheral and portal circulations reduced 3H-Ra to the normal range: 3.1 and 2.8 mg X kg-1 X min-1, respectively. Glucose recycling was also normalized by portal insulin infusion (20%) but was significantly decreased by peripheral infusion (11%, P less than 0.01). Thus the liver responds to lower infusion rates of insulin by the intraportal route, and only this mode of administration normalizes both hepatic glucose output and glucose recycling.

Use of [3-3H]glucose and [6-14C]glucose to measure glucose turnover and glucose metabolism in humans

1992 ◽  
Vol 263 (1) ◽  
pp. E17-E22 ◽  
Author(s):  
H. Katz ◽  
M. Homan ◽  
P. Butler ◽  
R. Rizza
Keyword(s):  
Indirect Calorimetry ◽  
Glucose Oxidation ◽  
Insulin Infusion ◽  
Specific Activity ◽  
Glucose Turnover ◽  
Detectable Effect ◽  
High Dose ◽  
Turnover Rates ◽  
Extracellular Glucose ◽  
Total Glucose

[3-3H]glucose is frequently used to measure glucose turnover in humans. If fructose 6-phosphate-fructose 1,6-diphosphate cycling (Fpc) is negligible in both liver and muscle, then [3-3H]- and [6-14C]glucose (corrected for Cori cycle activity) should provide equivalent measures of glucose turnover. In addition, if glycogenolysis is fully suppressed, then [14C]lactate specific activity should equal that of [6-14C]glucose from which it was derived, and oxidation of [6-14C]glucose, as measured by rate of generation of 14CO2, should equal total glucose oxidation (i.e., that derived from intra- and extracellular pools) as measured by indirect calorimetry. To address these questions, glucose turnover was measured simultaneously with [3-3H]- and [6-14C]glucose in the basal state and in presence of low (approximately 200 pM) and high (approximately 750 pM) insulin concentrations. Glucose turnover rates measured with [3-3H]- and [6-14C]glucose were equivalent at all insulin concentrations, indicating that Fpc had no detectable effect on measurement of glucose appearance. [14C]lactate specific activity was lower (P less than 0.01) than that of [6-14C]glucose in the basal state but not during either low- or high-dose insulin infusion, implying that all lactate was derived from extracellular glucose. On the other hand, glucose oxidation as measured by rate of generation of 14CO2 was lower (P less than 0.05) than glucose oxidation as measured by indirect calorimetry during both insulin infusions, implying either that suppression of glycogenolysis was not complete in all tissues or that one or both of these techniques do not accurately measure glucose oxidation.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of a selective rise in hepatic artery insulin on hepatic glucose production in the conscious dog

1999 ◽  
Vol 276 (4) ◽  
pp. E806-E813
Author(s):  
Dana K. Sindelar ◽  
Kayano Igawa ◽  
Chang A. Chu ◽  
Jim H. Balcom ◽  
Doss W. Neal ◽  
...  
Keyword(s):  
Portal Vein ◽  
Hepatic Artery ◽  
Insulin Infusion ◽  
Hepatic Glucose Production ◽  
Control Period ◽  
Glucose Production ◽  
Insulin Level ◽  
Hepatic Glucose ◽  
Glucose Output ◽  
Selective Increase

In the present study we compared the hepatic effects of a selective increase in hepatic sinusoidal insulin brought about by insulin infusion into the hepatic artery with those resulting from insulin infusion into the portal vein. A pancreatic clamp was used to control the endocrine pancreas in conscious overnight-fasted dogs. In the control period, insulin was infused via peripheral vein and the portal vein. After the 40-min basal period, there was a 180-min test period during which the peripheral insulin infusion was stopped and an additional 1.2 pmol ⋅ kg−1⋅ min−1of insulin was infused into the hepatic artery (HART, n = 5) or the portal vein (PORT, n = 5, data published previously). In the HART group, the calculated hepatic sinusoidal insulin level increased from 99 ± 20 (basal) to 165 ± 21 pmol/l (last 30 min). The calculated hepatic artery insulin concentration rose from 50 ± 8 (basal) to 289 ± 19 pmol/l (last 30 min). However, the overall arterial (50 ± 8 pmol/l) and portal vein insulin levels (118 ± 24 pmol/l) did not change over the course of the experiment. In the PORT group, the calculated hepatic sinusoidal insulin level increased from 94 ± 30 (basal) to 156 ± 33 pmol/l (last 30 min). The portal insulin rose from 108 ± 42 (basal) to 192 ± 42 pmol/l (last 30 min), whereas the overall arterial insulin (54 ± 6 pmol/l) was unaltered during the study. In both groups hepatic sinusoidal glucagon levels remained unchanged, and euglycemia was maintained by peripheral glucose infusion. In the HART group, net hepatic glucose output (NHGO) was suppressed from 9.6 ± 2.1 μmol ⋅ kg−1⋅ min−1(basal) to 4.6 ± 1.0 μmol ⋅ kg−1⋅ min−1(15 min) and eventually fell to 3.5 ± 0.8 μmol ⋅ kg−1⋅ min−1(last 30 min, P < 0.05). In the PORT group, NHGO dropped quickly ( P < 0.05) from 10.0 ± 0.9 (basal) to 7.8 ± 1.6 (15 min) and eventually reached 3.1 ± 1.1 μmol ⋅ kg−1⋅ min−1(last 30 min). Thus NHGO decreases in response to a selective increase in hepatic sinusoidal insulin, regardless of whether it comes about because of hyperinsulinemia in the hepatic artery or portal vein.

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 Arrestin domain-containing 3 (Arrdc3) modulates insulin action and glucose metabolism in liver

2020 ◽  
Vol 117 (12) ◽  
pp. 6733-6740 ◽  
Author(s):  
Thiago M. Batista ◽  
Sezin Dagdeviren ◽  
Shannon H. Carroll ◽  
Weikang Cai ◽  
Veronika Y. Melnik ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Insulin Action ◽  
Hepatic Glucose Production ◽  
Glycogen Synthesis ◽  
Glucose Production ◽  
Hepatic Glycogen ◽  
Glycogen Accumulation ◽  
Hepatic Glucose ◽  
Glucose Output

Insulin action in the liver is critical for glucose homeostasis through regulation of glycogen synthesis and glucose output. Arrestin domain-containing 3 (Arrdc3) is a member of the α-arrestin family previously linked to human obesity. Here, we show thatArrdc3is differentially regulated by insulin in vivo in mice undergoing euglycemic-hyperinsulinemic clamps, being highly up-regulated in liver and down-regulated in muscle and fat. Mice with liver-specific knockout (KO) of the insulin receptor (IR) have a 50% reduction inArrdc3messenger RNA, while, conversely, mice with liver-specific KO ofArrdc3(L-Arrdc3KO) have increased IR protein in plasma membrane. This leads to increased hepatic insulin sensitivity with increased phosphorylation of FOXO1, reduced expression of PEPCK, and increased glucokinase expression resulting in reduced hepatic glucose production and increased hepatic glycogen accumulation. These effects are due to interaction of ARRDC3 with IR resulting in phosphorylation of ARRDC3 on a conserved tyrosine (Y382) in the carboxyl-terminal domain. Thus,Arrdc3is an insulin target gene, and ARRDC3 protein directly interacts with IR to serve as a feedback regulator of insulin action in control of liver metabolism.

scholarly journals Effects of supplemental chromium and heat exposure on glucose metabolism and insulin action in sheep

2000 ◽  
Vol 134 (3) ◽  
pp. 319-325 ◽  
Author(s):  
H. SANO ◽  
S. KONNO ◽  
A. SHIGA
Keyword(s):  
Blood Glucose ◽  
Glucose Metabolism ◽  
Infusion Rate ◽  
Insulin Action ◽  
Heat Exposure ◽  
Glucose Infusion ◽  
Glucose Infusion Rate ◽  
Isotope Dilution Method ◽  
Glucose Turnover ◽  
Dilution Method

An isotope dilution method using [U-13C]glucose and a glucose clamp approach were applied to determine the effects of supplemental chromium (Cr) and heat exposure on blood glucose metabolism and tissue responsiveness and sensitivity to insulin in sheep. The sheep consumed diets with either 0 or 1 mg of Cr/kg (Control and +Cr diet, respectively) from high-Cr-yeast, and were exposed from a thermoneutral environment (20 °C) to a hot environment (30 °C) for 5 days. Blood glucose turnover rate did not differ between the diets, and was lower (P < 0·05) during heat exposure than in the thermoneutral environment. The maximal glucose infusion rate (tissue responsiveness to insulin) tended to be lower (P = 0·06) for the +Cr diet than for the Control diet, but did not change with heat exposure. The plasma insulin concentration at half maximal glucose infusion rate (tissue sensitivity to insulin) did not differ between the diets, and was greater (P < 0·05) during heat exposure than in the thermoneutral environment. No significant diet × environment interactions were observed. There was no significant evidence that Cr supplementation moderated heat stress in sheep from the measures of blood glucose metabolism and insulin action.

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