Enhanced hepatic gluconeogenic capacity for selected precursors after endurance training

1995 ◽  
Vol 79 (6) ◽  
pp. 1883-1888 ◽  
Author(s):  
K. D. Sumida ◽  
C. M. Donovan
Keyword(s):  
Oxygen Consumption ◽  
Endurance Training ◽  
Liver Perfusion ◽  
Glucose Production ◽  
Hepatic Gluconeogenesis ◽  
Bicarbonate Buffer ◽  
Hepatic Glucose ◽  
Urea Release ◽  
14Co2 Production ◽  
Glucose Output

The effects of endurance training (running 90 min/day, 30 m/min, approximately 10% grade) on hepatic gluconeogenesis were studied in 24-h-fasted rats by using the isolated liver perfusion technique. After isolation, livers were perfused (single pass) for 30 min with Krebs-Henseleit bicarbonate buffer and fresh bovine red blood cells (hematocrit 20–24%) with no added substrate. Alanine (10 mM), dihydroxyacetone (20 mM), or glutamine (10 mM) was then added to the reservoir, and perfusions continued for 60 min. No significant differences were observed in perfusate pH, hematocrit, bile production, or serum alanine aminotransferase effluxing from livers from trained or control animals for any perfusion. Livers from trained animals that were perfused with 10 mM alanine demonstrated significantly higher rates of glucose production compared with livers from control animals (0.51 +/- 0.04 vs. 0.40 +/- 0.02 micromol.min-1.g liver-1, respectively). Elevations of a similar magnitude were observed for rates of [14C]alanine incorporation into [14C]glucose in livers from trained vs. control animals (8,797 +/- 728 vs. 6,962 +/- 649 dpm.min-1.g liver-1, respectively). Significant increases were also observed in hepatic alanine uptake (30%), oxygen consumption (23%), urea release (22%), and 14CO2 production (29%) of livers of endurance-trained animals. In contrast, no significant differences between groups were observed for hepatic glucose output after perfusions with either dihydroxyacetone (1.75 +/- 0.06 micromol.min-1.g liver-1) or glutamine (0.62 +/- 0.04 micromol.min-1.g liver-1). Further, during perfusions with dihydroxyacetone and glutamine, training had no significant impact on precursor uptake, oxygen consumption, or urea output. The current findings indicate a training-induced adaptation for hepatic gluconeogenesis located below the level of the triose phosphates.

Enhanced gluconeogenesis from lactate in perfused livers after endurance training

1993 ◽  
Vol 74 (2) ◽  
pp. 782-787 ◽  
Author(s):  
K. D. Sumida ◽  
J. H. Urdiales ◽  
C. M. Donovan
Keyword(s):  
Endurance Training ◽  
Hepatic Glucose Production ◽  
Liver Perfusion ◽  
Glucose Production ◽  
Hepatic Gluconeogenesis ◽  
Bicarbonate Buffer ◽  
Hepatic Glucose ◽  
14Co2 Production ◽  
Glucose Output ◽  
And Control

The effects of endurance training (running 90 min/day at 30 m/min, 10% grade) on hepatic gluconeogenesis were studied in 24-h-fasted rats with use of the isolated liver perfusion technique. After isolation, the liver was perfused (single pass) for 30 min with Krebs-Henseleit bicarbonate buffer and fresh bovine erythrocytes (hematocrit 22–24%) with no added substrate. Subsequent to the "washout" period, the reservoir was elevated with various concentrations of lactate and [U-14C]lactate (10,000 dpm/ml) to assess hepatic glucose production. Relative flow rates were not significantly different between trained (1.94 +/- 0.05 ml/g liver) and control livers (1.91 +/- 0.05 ml/g liver). Furthermore, no significant differences were observed in perfusate pH, hematocrit, bile production, or serum alanine aminotransferase effluxing from trained or control livers. At saturating arterial lactate concentrations (> 2 mM), the maximal rate (Vmax) for hepatic glucose production was significantly higher for trained (0.91 +/- 0.04 mumol.min-1 x g liver-1) than for control livers (0.73 +/- 0.02 mumol.min-1 x g liver-1). That this reflected increased gluconeogenesis is supported by a significant elevation in the Vmax for [14C]glucose production from trained (13,150 +/- 578 dpm.min-1 x g liver-1) compared with control livers (10,712 +/- 505 dpm.min-1 x g liver-1). Significant increases were also observed in the Vmax for lactate uptake (25%), O2 consumption (19%), and 14CO2 production (23%) from endurance-trained livers. The Km for hepatic glucose output, approximately 1.05 mM lactate, was unchanged after endurance training. These findings demonstrate that chronic physical activity results in an elevated capacity for hepatic gluconeogenesis, as assessed in situ at saturating lactate concentrations.

scholarly journals P0950EFFECT OF THYROID HORMONE TREATMENT ON RENAL REABSORPTION OF GLUCOSE IN ALLOXAN-INDUCED DIABETIC RATS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Gireesh Dayma
Keyword(s):  
Blood Glucose ◽  
Thyroid Hormone ◽  
Glucose Homeostasis ◽  
Hepatic Glucose Production ◽  
Liver Perfusion ◽  
Glucose Production ◽  
Diabetic Rats ◽  
Hepatic Glucose ◽  
Glucose Output ◽  
Renal Expression

Abstract Background and Aims The thyroid hormone (TH) plays an important role in glucose metabolism. Recently, we showed that the TH improves glycemia control by decreasing cytokines expression in the adipose tissue and skeletal muscle of alloxan-induced diabetic rats, which were also shown to present primary hypothyroidism. In this context, this study aims to investigate whether the chronic treatment of diabetic rats with T3 could affect other tissues that are involved in the control of glucose homeostasis, as the liver and kidney. Method Adult male Wistar rats were divided into nondiabetic, diabetic, and diabetic treated with T3 (1.5 ?g/100 g BW for 4 weeks). Diabetes was induced by alloxan monohydrate (150 mg/kg, BW, i.p.). Animals showing fasting blood glucose levels greater than 250 mg/dL were selected for the study. Results After treatment, we measured the blood glucose, serum T3, T4, TSH, and insulin concentration, hepatic glucose production by liver perfusion, liver PEPCK, GAPDH, and pAKT expression, as well as urine glucose concentration and renal expression of SGLT2 and GLUT2. T3 reduced blood glucose, hepatic glucose production, liver PEPCK, GAPDH, and pAKT content and the renal expression of SGLT2 and increased glycosuria. Conclusion Results suggest that the decreased hepatic glucose output and increased glucose excretion induced by T3 treatment are important mechanisms that contribute to reduce serum concentration of glucose, accounting for the improvement of glucose homeostasis control in diabetic rats.

scholarly journals Berberine Attenuates Hyperglycemia by Inhibiting the Hepatic Glucagon Pathway in Diabetic Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Ying Zhong ◽  
Jing Jin ◽  
Peiyu Liu ◽  
Yu Song ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Intracellular Camp ◽  
Diabetic Mice ◽  
Hepatic Gluconeogenesis ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Hepatic Glucose ◽  
Glucose Output

Dysregulated glucagon drives hyperfunction in hepatic glucose output, which is the main cause of persistent hyperglycemia in type 2 diabetes. Berberine (Zhang et al., 2010) has been used as a hypoglycemic agent, yet the mechanism by which BBR inhibits hepatic gluconeogenesis remains incompletely understood. In this study, we treated diabetic mice with BBR, tested blood glucose levels, and then performed insulin, glucose lactate, and glucagon tolerance tests. Intracellular cAMP levels in hepatocytes were determined by ELISA, hepatic gluconeogenetic genes were assayed by RT-qPCR, and the phosphorylation of CREB, which is the transcriptional factor controlling the expression of gluconeogenetic genes, was detected by western blot. BBR reduced blood glucose levels, improved insulin and glucose tolerance, and suppressed lactate- and glucagon-induced hepatic gluconeogenesis in ob/ob and STZ-induced diabetic mice. Importantly, BBR blunted glucagon-induced glucose production and gluconeogenic gene expression in hepatocytes, presumably through reducing cAMP, which resulted in the phosphorylation of CREB. By utilizing a cAMP analogue, adenylate cyclase (AC), to activate cAMP synthetase, and an inhibitor of the cAMP degradative enzyme, phosphodiesterase (PDE), we revealed that BBR accelerates intracellular cAMP degradation. BBR reduces the intracellular cAMP level by activating PDE, thus blocking activation of downstream CREB and eventually downregulating gluconeogenic genes to restrain hepatic glucose production.

Effects of epinephrine on the net hepatic uptake of lactate, pyruvate, and glycerol in sheep

1991 ◽  
Vol 69 (4) ◽  
pp. 475-479 ◽  
Author(s):  
Ronald P. Brockman
Keyword(s):  
Blood Vessels ◽  
Glucose Production ◽  
Hepatic Uptake ◽  
Metabolic Clearance ◽  
Hepatic Extraction ◽  
Hepatic Glucose Output ◽  
Epinephrine Infusion ◽  
Hepatic Gluconeogenesis ◽  
Hepatic Glucose ◽  
Glucose Output

Epinephrine causes hyperglycemia in part by increasing gluconeogenesis. However, the mechanism of its gluconeogenic effects has not been studied in ruminants. This study was undertaken to examine the effect of epinephrine on the net hepatic uptake of selected glucose precursors in sheep. The major abdominal blood vessels of the sheep were catheterized in normal and alloxan diabetic sheep. Glucose production, metabolic clearance of glucose, and the hepatic removal of certain glucose precursors were determined before, during, and after epinephrine infusion. Epinephrine increased the hepatic glucose output, the concentrations of lactate and glycerol in plasma, and the net hepatic uptake and fractional hepatic extraction of lactate and glycerol. These effects were independent of changes in the concentrations of insulin and glucagon in plasma. These results show that epinephrine directly stimulates hepatic gluconeogenesis in sheep.Key words: epinephrine, hepatic gluconeogenesis, sheep.

scholarly journals Coordinated changes in hepatic amino acid metabolism and endocrine signals support hepatic glucose production during fetal hypoglycemia

2015 ◽  
Vol 308 (4) ◽  
pp. E306-E314 ◽  
Author(s):  
Satya S. Houin ◽  
Paul J. Rozance ◽  
Laura D. Brown ◽  
William W. Hay ◽  
Randall B. Wilkening ◽  
...  
Keyword(s):  
Fetal Liver ◽  
Hepatic Glucose Production ◽  
Plasma Concentrations ◽  
Glucose Production ◽  
Late Gestation ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Hepatic Glucose ◽  
Molar Percent ◽  
Glucose Output

Reduced fetal glucose supply, induced experimentally or as a result of placental insufficiency, produces an early activation of fetal glucose production. The mechanisms and substrates used to fuel this increased glucose production rate remain unknown. We hypothesized that in response to hypoglycemia, induced experimentally with maternal insulin infusion, the fetal liver would increase uptake of lactate and amino acids (AA), which would combine with hormonal signals to support hepatic glucose production. To test this hypothesis, metabolic studies were done in six late gestation fetal sheep to measure hepatic glucose and substrate flux before (basal) and after [days (d)1 and 4] the start of hypoglycemia. Maternal and fetal glucose concentrations decreased by 50% on d1 and d4 ( P < 0.05). The liver transitioned from net glucose uptake (basal, 5.1 ± 1.5 μmol/min) to output by d4 (2.8 ± 1.4 μmol/min; P < 0.05 vs. basal). The [U-13C]glucose tracer molar percent excess ratio across the liver decreased over the same period (basal: 0.98 ± 0.01, vs. d4: 0.89 ± 0.01, P < 0.05). Total hepatic AA uptake, but not lactate or pyruvate uptake, increased by threefold on d1 ( P < 0.05) and remained elevated throughout the study. This AA uptake was driven largely by decreased glutamate output and increased glycine uptake. Fetal plasma concentrations of insulin were 50% lower, while cortisol and glucagon concentrations increased 56 and 86% during hypoglycemia ( P < 0.05 for basal vs. d4). Thus increased hepatic AA uptake, rather than pyruvate or lactate uptake, and decreased fetal plasma insulin and increased cortisol and glucagon concentrations occur simultaneously with increased fetal hepatic glucose output in response to fetal hypoglycemia.

Involvement of the vagus nerves in the regulation of basal hepatic glucose production in conscious dogs

2002 ◽  
Vol 283 (5) ◽  
pp. E958-E964 ◽  
Author(s):  
Sylvain Cardin ◽  
Konstantin Walmsley ◽  
Doss W. Neal ◽  
Phillip E. Williams ◽  
Alan D. Cherrington
Keyword(s):  
Hepatic Glucose Production ◽  
Control Period ◽  
Glucose Production ◽  
Heart Rate Change ◽  
Vagus Nerves ◽  
Hepatic Glucose Metabolism ◽  
Vagal Blockade ◽  
Hepatic Glucose ◽  
Cooling Coils ◽  
Glucose Output

We determined if blocking transmission in the fibers of the vagus nerves would affect basal hepatic glucose metabolism in the 18-h-fasted conscious dog. A pancreatic clamp (somatostatin, basal portal insulin, and glucagon) was employed. A 40-min control period was followed by a 90-min test period. In one group, stainless steel cooling coils (Sham, n = 5) were perfused with a 37°C solution, while in the other (Cool, n = 6), the coils were perfused with −20°C solution. Vagal blockade was verified by heart rate change (80 ± 9 to 84 ± 14 beats/min in Sham; 98 ± 12 to 193 ± 22 beats/min in Cool). The arterial glucose level was kept euglycemic by glucose infusion. No change in tracer-determined glucose production occurred in Sham, whereas in Cool it dropped significantly (2.4 ± 0.4 to 1.9 ± 0.4 mg · kg−1· min−1). Net hepatic glucose output did not change in Sham but decreased from 1.9 ± 0.3 to 1.3 ± 0.3 mg · kg−1· min−1in the Cool group. Hepatic gluconeogenesis did not change in either group. These data suggest that vagal blockade acutely modulates hepatic glucose production by inhibiting glycogenolysis.

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.

Increased hepatic glucose production response to glucagon in trained subjects

1998 ◽  
Vol 274 (1) ◽  
pp. E23-E28 ◽  
Author(s):  
Réjean Drouin ◽  
Carole Lavoie ◽  
Josée Bourque ◽  
Francine Ducros ◽  
Danielle Poisson ◽  
...  
Keyword(s):  
Endurance Training ◽  
Hepatic Glucose Production ◽  
Area Under The Curve ◽  
Glucose Production ◽  
Trained Subjects ◽  
Endogenous Insulin ◽  
Hepatic Glucose ◽  
Glucagon And Insulin ◽  
The Impact ◽  
Male Subjects

This study was designed to characterize the impact of endurance training on the hepatic response to glucagon. We measured the effect of glucagon on hepatic glucose production (HGP) in resting trained ( n = 8) and untrained ( n = 8) healthy male subjects (maximal rate of O2 consumption: 65.9 ± 1.6 vs. 46.8 ± 0.6 ml O2 ⋅ kg−1 ⋅ min−1, respectively, P < 0.001). Endogenous insulin and glucagon were suppressed by somatostatin (somatotropin release-inhibiting hormone) infusion (450 μg/h) over 4 h. Insulin (0.15 mU ⋅ kg−1 ⋅ min−1) was infused throughout the study, and glucagon (1.5 ng ⋅ kg−1 ⋅ min−1) was infused over the last 2 h. During the latter period, plasma glucagon and insulin remained constant at 138.2 ± 3.1 vs. 145.3 ± 2.1 ng/l and at 95.5 ± 4.5 vs. 96.2 ± 1.9 pmol/l in trained and untrained subjects, respectively. Plasma glucose increased and peaked at 11.4 ± 1.1 mmol/l in trained subjects and at 8.9 ± 0.8 mmol/l in untrained subjects ( P < 0.001). During glucagon stimulation, the mean increase in HGP area under the curve was 15.8 ± 2.8 mol ⋅ kg−1 ⋅ min−1in trained subjects compared with 7.4 ± 1.6 mol ⋅ kg−1 ⋅ min−1in untrained subjects ( P < 0.01) over the first hour and declined to 6.8 ± 2.8 and 4.9 ± 1.4 mol ⋅ kg−1 ⋅ min−1during the second hour. In conclusion, these observations indicate that endurance training is associated with an increase in HGP in response to physiological levels of glucagon, thus suggesting an increase in hepatic glucagon sensitivity.

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 Unlike mice, dogs exhibit effective glucoregulation during low-dose portal and peripheral glucose infusion

2004 ◽  
Vol 286 (2) ◽  
pp. E226-E233 ◽  
Author(s):  
Mary Courtney Moore ◽  
Sylvain Cardin ◽  
Dale S. Edgerton ◽  
Ben Farmer ◽  
Doss W. Neal ◽  
...  
Keyword(s):  
Low Dose ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Hepatic Glucose Output ◽  
Arterial Blood ◽  
Hepatic Glucose ◽  
Arterial Blood Glucose ◽  
Hepatic Portal ◽  
Glucose Output ◽  
Arteriovenous Difference

Portal infusion of glucose in the mouse at a rate equivalent to basal endogenous glucose production causes hypoglycemia, whereas peripheral infusion at the same rate causes significant hyperglycemia. We used tracer and arteriovenous difference techniques in conscious 42-h-fasted dogs to determine their response to the same treatments. The studies consisted of three periods: equilibration (100 min), basal (40 min), and experimental (180 min), during which glucose was infused at 13.7 μmol· kg–1·min–1 into a peripheral vein (PE, n = 5) or the hepatic portal (PO, n = 5) vein. Arterial blood glucose increased ∼0.8 mmol/l in both groups. Arterial and hepatic sinusoidal insulin concentrations were not significantly different between groups. PE exhibited an increase in nonhepatic glucose uptake (non-HGU; Δ8.6 ± 1.2 μmol·kg–1·min–1) within 30 min, whereas PO showed a slight suppression (Δ–3.7 ± 3.1 μmol·kg–1·min–1). PO shifted from net hepatic glucose output (NHGO) to uptake (NHGU; 2.5 ± 2.8 μmol·kg–1·min–1) within 30 min, but PE still exhibited NHGO (6.0 ± 1.9 μmol·kg–1·min–1) at that time and did not initiate NHGU until after 90 min. Glucose rates of appearance and disappearance did not differ between groups. The response to the two infusion routes was markedly different. Peripheral infusion caused a rapid enhancement of non-HGU, whereas portal delivery quickly activated NHGU. As a result, both groups maintained near-euglycemia. The dog glucoregulates more rigorously than the mouse in response to both portal and peripheral glucose delivery.

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