Metabolic role of the exercise-induced increment in epinephrine in the dog

Moates, J. M.; Lacy, D. Brooks; Goldstein, Richard E.; Cherrington, Alan D.; Wasserman, David H.

doi:10.1152/ajpendo.1988.255.4.e428

Cited by 18 publications

(18 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mobilization of glucose in the basal pancreatic hormone group was equal to that seen in dogs that remained sedentary. The levels of NHGO seen in EX-Sim dogs (ϳ8 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 ) were identical to NHGO in previous work where artificial hormonal manipulation was not used in dogs exercising at a similar intensity (4,5,16), and the increment in NHGO from basal was consistent with increases in the rate of whole-body glucose appearance previously seen (15,(17)(18)(19). The primary source of the increased glucose production during 150 min of exercise is hepatic glycogenolysis in the 18-h fasted dog (20).…”

Section: Discussionsupporting

confidence: 82%

Exercise-Induced Changes in Insulin and Glucagon Are Not Required for Enhanced Hepatic Glucose Uptake After Exercise but Influence the Fate of Glucose Within the Liver

et al. 2004

View full text Add to dashboard Cite

To test whether pancreatic hormonal changes that occur during exercise are necessary for the postexercise enhancement of insulin-stimulated net hepatic glucose uptake, chronically catheterized dogs were exercised on a treadmill or rested for 150 min. At the onset of exercise, somatostatin was infused into a peripheral vein, and insulin and glucagon were infused in the portal vein to maintain basal levels (EX-Basal) or simulate the response to exercise (EX-Sim). Glucose was infused as needed to maintain euglycemia during exercise. After exercise or rest, somatostatin infusion was continued in exercised dogs and initiated in dogs that had remained sedentary. In addition, basal glucagon, glucose, and insulin were infused in the portal vein for 150 min to create a hyperinsulinemic-hyperglycemic clamp in EXBasal, EX-Sim, and sedentary dogs. Steady-state measurements were made during the final 50 min of the clamp. During exercise, net hepatic glucose output (mg ⅐ kg ؊1 ⅐ min ؊1 ) rose in EX-Sim (7.6 ؎ 2.8) but not EX-Basal (1.9 ؎ 0.3) dogs. During the hyperinsulinemichyperglycemic clamp that followed either exercise or rest, net hepatic glucose uptake (mg ⅐ kg ؊1 ⅐ min ؊1 ) was elevated in both EX-Basal (4.0 ؎ 0.7) and EX-Sim (4.6 ؎ 0.5) dogs compared with sedentary dogs (2.0 ؎ 0.3). Despite this elevation in net hepatic glucose uptake after exercise, glucose incorporation into hepatic glycogen, determined using [3-3 H]glucose, was not different in EX-Basal and sedentary dogs, but was 50 ؎ 30% greater in EX-Sim dogs. Exercise-induced changes in insulin and glucagon, and consequent glycogen depletion, are not required for the increase in net hepatic glucose uptake after exercise but result in a greater fraction of the glucose consumed by the liver being directed to glycogen. Diabetes 53:3041-3047, 2004 S ustained exercise has been shown to improve net hepatic glucose uptake (NHGU) and enhance hepatic glycogen synthesis (1,2). Our previous work has shown that the enhanced NHGU during a glucose load after exercise is due to improvements in hepatic insulin action (2). Although exercise clearly improves insulin-stimulated NHGU, it is not known what part of the exercise response leads to the postexercise enhancement in NHGU.During exercise, hepatic glycogen stores are mobilized and gluconeogenesis is accelerated to help meet the increased energy demands of working muscle. Previous work in the dog has shown that the changes in insulin and glucagon during exercise are essential to the regulation of hepatic glucose output during exercise (3), and preventing the fall in insulin (4) and the rise in glucagon (5) attenuates the glycogenolytic and gluconeogenic responses seen during exercise. In particular, the depletion of liver glycogen is likely to have persistent effects.Interestingly, work in hepatocytes has shown that hepatic glycogen synthesis is inversely proportional to hepatic glycogen content, suggesting that hepatic glycogen may play a role in the regulation of its own synthesis (6). Additionally sustained fasting, a co...

show abstract

Section: Discussionsupporting

confidence: 82%

Exercise-Induced Changes in Insulin and Glucagon Are Not Required for Enhanced Hepatic Glucose Uptake After Exercise but Influence the Fate of Glucose Within the Liver

et al. 2004

View full text Add to dashboard Cite

show abstract

“…hydrocortisone. This therapeutic regimen has been shown to result in normal electrolyte and metabolic parameters (23). Nine days before the experiment, a second surgical procedure was performed under general anesthesia to place catheters in both common carotid arteries and both vertebral arteries, as previously described (20).…”

Section: Methodsmentioning

confidence: 99%

In the Absence of Counterregulatory Hormones, the Increase in Hepatic Glucose Production During Insulin-Induced Hypoglycemia in the Dog Is Initiated in the Liver Rather Than the Brain

et al. 1996

View full text Add to dashboard Cite

We have previously demonstrated that the liver can release glucose in response to insulin-induced hypoglycemia, despite the absence of glucagon, epinephrine, cortisol, and growth hormone. The aim of this study was to determine whether this is activated by liver or brain hypoglycemia. We assessed the response to insulin-induced hypoglycemia in the absence of counterregulatory hormones in overnight-fasted conscious adrenalectomized dogs that were given somatostatin and intraportal insulin (30 pmol x kg(-1) x min(-1)) for 360 min. Glucose was infused to maintain euglycemia for 3 h and then to allow limited peripheral hypoglycemia for the next 3 h. During peripheral hypoglycemia, five dogs received glucose via both carotid and vertebral arteries to maintain cerebral euglycemia (H-EU group) concurrently with peripheral hypoglycemia, while six dogs received saline in these vessels to allow simultaneous cerebral and peripheral hypoglycemia (H-HY group). Throughout the study, arterial insulin was 1,675 +/- 295 and 1,440 +/- 310 pmol/l in the H-HY and H-EU groups, respectively. Glucose fell from 6.2 +/- 0.3 to 2.1 +/- 0.0 mmol/l and from 5.8 +/- 0.3 to 1.9 +/- 0.1 mmol/l in the last hour in the H-HY and H-EU groups, respectively (P < 0.05 for both). Norepinephrine rose from 1.12 +/- 0.35 to 2.44 +/- 0.69 nmol/l and from 1.09 +/- 0.07 to 1.74 +/- 0.16 nmol/l in the last hour in the H-HY and H-EU groups, respectively (P < 0.05 for both; no difference between groups). Glucagon, epinephrine, and cortisol were below the limits of detection. The liver switched from uptake to output of glucose during peripheral hypoglycemia in both the H-HY (-7.1 +/- 2.1 to 5.4 +/- 3.1 micromol x kg(-1) x min(-1)) and H-EU (-7.9 +/- 3.5 to 3.4 +/- 1.7 micromol x kg(-1) x min(-1)) groups (P < 0.05 for both; no difference between groups). Alanine levels and net hepatic alanine uptake fell similarly in both groups. There were increases (P < 0.05) in glycerol (12 +/- 3 to 258 +/- 47 micromol/l) and nonesterified fatty acid (194 +/- 10 to 540 +/- 80 micromol/l) levels and in total ketone production (0.4 +/- 0.1 to 1.1 +/- 0.2 micromol x kg(-1) x min(-1)) in the H-HY group, but these parameters did not change in the H-EU group. These data clearly indicate that the lipolytic and hepatic responses to hypoglycemia are driven by differential sensing mechanisms. Thus, during insulin-induced hypoglycemia, when counterregulatory hormones are absent, liver hypoglycemia triggers the increase in hepatic glucose production, whereas cerebral hypoglycemia causes the increases in lipolysis and ketogenesis.

show abstract

“…The liver extracts glucagon, thereby slowing the time course and dampening the rise in the hormone in the peripheral circulation (Coker et al, 1999;Wasserman et al, 1993). It is unlikely that catecholamines are directly responsible for the increase in glucose production during exercise, as hepatic denervation (Wasserman et al, 1990), selective hepatic b-and aadrenergic receptor blockade (Coker et al, 1997) and adrenalectomy (Moates et al, 1988) have little or no effect in the exercising dog. These findings are consistent with research in other species, including humans (Wasserman, 1995).…”

Section: Control Of Muscle Glucose Influx During Exercisementioning

confidence: 99%

The physiological regulation of glucose flux into musclein vivo

Wasserman

Ayala

et al. 2011

Journal of Experimental Biology

137

106

View full text Add to dashboard Cite

Summary Skeletal muscle glucose uptake increases dramatically in response to physical exercise. Moreover, skeletal muscle comprises the vast majority of insulin-sensitive tissue and is a site of dysregulation in the insulin-resistant state. The biochemical and histological composition of the muscle is well defined in a variety of species. However, the functional consequences of muscle biochemical and histological adaptations to physiological and pathophysiological conditions are not well understood. The physiological regulation of muscle glucose uptake is complex. Sites involved in the regulation of muscle glucose uptake are defined by a three-step process consisting of: (1) delivery of glucose to muscle, (2) transport of glucose into the muscle by GLUT4 and (3) phosphorylation of glucose within the muscle by a hexokinase (HK). Muscle blood flow, capillary recruitment and extracellular matrix characteristics determine glucose movement from the blood to the interstitium. Plasma membrane GLUT4 content determines glucose transport into the cell. Muscle HK activity, cellular HK compartmentalization and the concentration of the HK inhibitor glucose 6-phosphate determine the capacity to phosphorylate glucose. Phosphorylation of glucose is irreversible in muscle; therefore, with this reaction, glucose is trapped and the uptake process is complete. Emphasis has been placed on the role of the glucose transport step for glucose influx into muscle with the past assertion that membrane transport is rate limiting. More recent research definitively shows that the distributed control paradigm more accurately defines the regulation of muscle glucose uptake as each of the three steps that define this process are important sites of flux control.

show abstract

Metabolic role of the exercise-induced increment in epinephrine in the dog

Cited by 18 publications

References 17 publications

Exercise-Induced Changes in Insulin and Glucagon Are Not Required for Enhanced Hepatic Glucose Uptake After Exercise but Influence the Fate of Glucose Within the Liver

Exercise-Induced Changes in Insulin and Glucagon Are Not Required for Enhanced Hepatic Glucose Uptake After Exercise but Influence the Fate of Glucose Within the Liver

In the Absence of Counterregulatory Hormones, the Increase in Hepatic Glucose Production During Insulin-Induced Hypoglycemia in the Dog Is Initiated in the Liver Rather Than the Brain

The physiological regulation of glucose flux into musclein vivo

Contact Info

Product

Resources

About