Biomedical subjects

D H Wasserman

Publications and source records attributed to D H Wasserman.

At least 37 records · Page 2Linked to original sources

PubMed1999

Zonation of acetate labeling across the liver: implications for studies of lipogenesis by MIDA.

Measurement of fractional lipogenesis by mass isotopomer distribution analysis (MIDA) of fatty acids or cholesterol labeled from [(13)C]acetate assumes constant enrichment of lipogenic acetyl-CoA in all hepatocytes. This would not be the case if uptake and release of acetate by the liver resulted in transhepatic gradients of acetyl-CoA enrichment. Conscious dogs, prefitted with transhepatic catheters, were infused with glucose and [1, 2-(13)C(2)]acetate. Stable concentrations and enrichments of acetate were measured in artery (17 microM, 36%), portal vein (61 microM, 5. 4%), and hepatic vein (17 microM, 1.0%) and were computed for mixed blood entering the liver (53 microM, 7.4%). We also measured balances of propionate and butyrate across gut and liver. All gut release of propionate and butyrate is taken up by the liver. The threefold decrease in acetate concentration and the sevenfold decrease in acetate enrichment across the liver strongly suggest that the enrichment of lipogenic acetyl-CoA decreases across the liver. Thus fractional hepatic lipogenesis measured in vivo by MIDA may be underestimated.

Acetates↗

PubMed1999

Role of a negative arterial-portal venous glucose gradient in the postexercise state.

UNLABELLED: Prior exercise stimulates muscle and liver glucose uptake. A negative arterial-portal venous glucose gradient (a-pv grad) stimulates resting net hepatic glucose uptake (NHGU) but reduces muscle glucose uptake. This study investigates the effects of a negative a-pv grad during glucose administration after exercise in dogs. EXPERIMENTAL PROTOCOL: exercise (-180 to -30 min), transition (-30 to -20 min), basal period (-20 to 0 min), and experimental period (0 to 100 min). In the experimental period, 130 mg/dl arterial hyperglycemia was induced via vena cava (Pe, n = 6) or portal vein (Po, n = 6) glucose infusions. Insulin and glucagon were replaced at fourfold basal and basal rates. During the experimental period, the a-pv grad (mg/dl) was 3 +/- 1 in Pe and -10 +/- 2 in Po. Arterial insulin and glucagon were similar in the two groups. In Pe, net hepatic glucose balance (mg x kg(-1) x min(-1), negative = uptake) was 4.2 +/- 0.3 (basal period) and -1.2 +/- 0.3 (glucose infusion); in Po it was 4.1 +/- 0.5 and -3.2 +/- 0.4, respectively (P < 0.005 vs. Pe). Total glucose infusion (mg x kg(-1) x min(-1)) was 11 +/- 1 in Po and 8 +/- 1 in Pe (P < 0.05). Net hindlimb and whole body nonhepatic glucose uptakes were similar. CONCLUSIONS: the portal signal independently stimulates NHGU after exercise. Conversely, prior exercise eliminates the inhibitory effect of the portal signal on glucose uptake by nonhepatic tissues. The portal signal therefore increases whole body glucose disposal after exercise by an amount equal to the increase in NHGU.

Alanine↗

PubMed1999

Pancreatic innervation is not essential for exercise-induced changes in glucagon and insulin or glucose kinetics.

The purpose of this study was to determine the role of pancreatic innervation in mediating exercise-induced changes in pancreatic hormone secretion and glucose kinetics. Dogs underwent surgery >16 days before an experiment, at which time flow probes were implanted on the portal vein and the hepatic artery, and Silastic catheters were inserted in the carotid artery, portal vein, and hepatic vein for sampling. In one group of dogs (DP) all nerves and plexuses to the pancreas were sectioned during surgery. A second group of dogs underwent sham denervation (SHAM). Pancreatic tissue norepinephrine was reduced by >98% in DP dogs. Each study consisted of basal (-30 to 0 min) and moderate exercise (0 to 150 min, 100 m/min, 12% grade) periods. Isotope ([3-(3)H]glucose) dilution and arteriovenous differences were used to assess hepatic function. Arterial and portal vein glucagon and insulin concentrations and the rate of net extrahepatic splanchnic glucagon release (NESGR) were similar in DP and SHAM during the basal period. Arterial and portal vein glucagon and NESGR increased similarly in DP and SHAM during exercise. Arterial and portal vein insulin were similar during exercise. Arterial glucose, tracer-determined endogenous glucose production, and net hepatic glucose output were similar in DP and SHAM during the basal and exercise periods. These results demonstrate that pancreatic nerves are not essential to pancreatic hormone secretion or glucose homeostasis during rest or moderate exercise.

Animals↗

PubMed1999

Splanchnic glucagon kinetics in exercising alloxan-diabetic dogs.

The purpose of this study was to define the relationship between arterial immunoreactive glucagon (IRG) and IRG that perfuses the liver via the portal vein during exercise in the diabetic state. Dogs underwent surgery >16 days before the experiment, at which time flow probes were implanted in the portal vein and the hepatic artery, and Silastic catheters were inserted in the carotid artery, portal vein, and hepatic vein for sampling. Dogs were made diabetic with alloxan injected intravenously approximately 3 wk before study (AD) or were studied in the nondiabetic state (ND). Each study consisted of a 30-min basal period and a 150-min moderate-exercise period on a treadmill. The findings from these studies indicate that the exercise-induced increment in portal vein IRG can be substantially greater in AD compared with ND, even when arterial and hepatic vein increments are not different. The larger IRG gradient from the portal vein to the systemic circulation in AD dogs is a function of a twofold greater increase in nonhepatic splanchnic IRG release and a fivefold greater hepatic fractional IRG extraction during exercise. In conclusion, during exercise, arterial IRG concentrations greatly underestimate the IRG levels to which the liver is exposed in ND, and this underestimation is considerably greater in dogs with poorly controlled diabetes.

Animals↗

PubMed1998

An overview of muscle glucose uptake during exercise. Sites of regulation.

The uptake of blood glucose by skeletal muscle is a complex process. In order to be metabolized, glucose must travel the path from blood to interstitium to intracellular space and then be phosphorylated to glucose 6-phosphate (G6P). Movement of glucose from blood to interstitium is determined by skeletal muscle blood flow, capillary recruitment and the endothelial permeability to glucose. The influx of glucose from the interstitium to intracellular space is determined by the number of glucose transporters in the sarcolemma and the glucose gradient across the sarcolemma. The capacity to phosphorylate glucose is determined by the amount of skeletal muscle hexokinase II, hexokinase II compartmentalization within the cell, and the concentration of the hexokinase II inhibitor G6P. Any change in glucose uptake occurs due to an alteration in one or more of these steps. Based on the low calculated intracellular glucose levels and the higher affinity of glucose for phosphorylation relative to transport, glucose transport is generally considered rate-determining for basal muscle glucose uptake. Exercise increases both the movement of glucose from blood to sarcolemma and the permeability of the sarcolemma to glucose. Whether the ability to phosphorylate glucose is increased in the working muscle remains to be clearly shown. It is possible that the accelerated glucose delivery and transport rates during exercise bias regulation so that muscle glucose phosphorylation exerts more control on muscle glucose uptake. Conditions that alter glucose uptake during exercise, such as increased NEFA concentrations, decreased oxygen availability and adrenergic stimulation, must work by altering one or more of the three steps involved in glucose uptake. This review describes the regulation of glucose uptake during exercise at each of these sites under a number of conditions, as well as describing muscle glucose uptake in the post-exercise state.

Animals↗

PubMed1998

Analysis of insulin-stimulated skeletal muscle glucose uptake in conscious rat using isotopic glucose analogs.

An isotopic method was used in conscious rats to determine the roles of glucose transport and the transsarcolemmal glucose gradient (TSGG) in control of basal and insulin-stimulated muscle glucose uptake. Rats received an intravenous 3-O-[3H]methylglucose (3-O-[3H]MG) infusion from -100 to 40 min and a 2-deoxy-[3H]glucose infusion from 0 to 40 min to calculate a glucose metabolic index (Rg). Insulin was infused from -100 to 40 min at rates of 0.0, 0.6, 1.0, and 4.0 mU.kg-1.min-1, and glucose was clamped at basal concentrations. The ratios of soleus intracellular to extracellular 3-O-[3H]MG concentration and soleus glucose concentrations were used to estimate the TSGG using principles of glucose counter-transport. Tissue glucose concentrations were compared in well-perfused, slow-twitch muscle (soleus) and poorly perfused, fast-twitch muscle (vastus lateralis, gastrocnemius). Data show that 1) small increases in insulin increase soleus Rg without decreasing TSGG, suggesting that muscle glucose delivery and phosphorylation can accommodate the increased flux; 2) due to a limitation in soleus glucose phosphorylation and possibly delivery, insulin at high physiological levels decreases TSGG, and at supraphysiological insulin levels the TSGG is not significantly different from 0; 3) maximum Rg is maintained even though TSGG decreases with increasing insulin levels, indicating that glucose transport continues to increase and is not rate limiting for maximal insulin-stimulated glucose uptake; and 4) muscle consisting of fast-twitch fibers that are poorly perfused exhibits a 35-45% fall in tissue glucose with insulin, suggesting that glucose delivery is a major limitation in sustaining the TSGG. In conclusion, control of glucose uptake is distributed between glucose transport and factors that determine the TSGG. Insulin stimulation of glucose transport increases the demands on the factors that maintain glucose delivery to the muscle membrane and glucose phosphorylation inside the muscle.

3-O-Methylglucose↗

PubMed1998

A negative arterial-portal venous glucose gradient decreases skeletal muscle glucose uptake.

The effect of a negative arterial-portal venous (a-pv) glucose gradient on skeletal muscle and whole body nonhepatic glucose uptake was studied in 12 42-h-fasted conscious dogs. Each study consisted of a 110-min equilibration period, a 30-min baseline period, and two 120-min hyperglycemic (2-fold basal) periods (either peripheral or intraportal glucose infusion). Somatostatin was infused along with insulin (3 x basal) and glucagon (basal). Catheters were inserted 17 days before studies in the external iliac artery and hepatic, portal and common iliac veins. Blood flow was measured in liver and hindlimb using Doppler flow probes. The arterial blood glucose, arterial plasma insulin, arterial plasma glucagon, and hindlimb glucose loads were similar during peripheral and intraportal glucose infusions. The a-pv glucose gradient (in mg/dl) was 5 +/- 1 during peripheral and -18 +/- 3 during intraportal glucose infusion. The net hindlimb glucose uptakes (in mg/min) were 5.0 +/- 1.2, 20.4 +/- 4.5, and 14.8 +/- 3.2 during baseline, peripheral, and intraportal glucose infusion periods, respectively (P < 0.01, peripheral vs. intraportal); the hindlimb glucose fractional extractions (in %) were 2.8 +/- 0.4, 4.7 +/- 0.8, and 3.9 +/- 0.5 during baseline, peripheral, and intraportal glucose infusions, respectively (P < 0. 05, peripheral vs. intraportal). The net whole body nonhepatic glucose uptakes (in mg . kg-1 . min-1) were 1.6 +/- 0.1, 7.9 +/- 1.3, and 5.4 +/- 1.1 during baseline, peripheral, and intraportal glucose infusion, respectively (P < 0.05, peripheral vs. intraportal). In the liver, net glucose uptake was 70% greater during intraportal than during peripheral glucose infusion (5.8 +/- 0.7 vs. 3.4 +/- 0.4 mg . kg-1 . min-1). In conclusion, despite comparable glucose loads and insulin levels, hindlimb and whole body net nonhepatic glucose uptake decreased significantly during portal venous glucose infusion, suggesting that a negative a-pv glucose gradient leads to an inhibitory signal in nonhepatic tissues, among which skeletal muscle appears to be the most important.

Animals↗

PubMed1998

Regulation of hepatic glutamine metabolism during exercise in the dog.

The goal of this study was to determine how liver glutamine (Gln) metabolism adapts to acute exercise in the 18-h-fasted dogs (n = 7) and in dogs that were glycogen depleted by a 42-h fast (n = 8). For this purpose, sampling (carotid artery, portal vein, and hepatic vein) and infusion (vena cava) catheters and Doppler flow probes (portal vein, hepatic artery) were implanted under general anesthesia. At least 16 days later an experiment, consisting of a 120-min equilibration period, a 30-min basal sampling period, and a 150-min exercise period was performed. At the start of the equilibration period, a constant-rate infusion of [5-15N]Gln was initiated. Arterial Gln flux was determined by isotope dilution. Gut and liver Gln release into and uptake from the blood were calculated by combining stable isotopic and arteriovenous difference methods. The results of this study show that 1) in the 18-h-fasted dog, approximately 10% and approximately 35% of the basal Gln appearance in arterial blood is due to Gln release from the gut and liver, respectively, whereas approximately 30% and approximately 25% of the basal Gln disappearance is due to removal by these tissues; 2) extending the fast to 42 h does not affect basal arterial Gln flux or the contribution of the gut to arterial Gln fluxes but decreases hepatic Gln release, causing a greater retention of gluconeogenic carbon by the liver; 3) moderate-intensity exercise increases hepatic Gln removal from the blood regardless of fast duration but does not affect the hepatic release of Gln; and 4) Gln plays an important role in channeling nitrogen into the ureagenic pathway in the basal state, and this role is increased by approximately 80% in response to exercise. These studies illustrate the quantitative importance of the splanchnic bed contribution to arterial Gln flux during exercise and the ability of the liver to acutely adapt to changes in metabolic requirements induced by the combined effects of fasting and exercise.

Animals↗

PubMed1998

Enhanced muscle glucose uptake facilitates nitrogen efflux from exercised muscle.

The hypothesis that glucose ingestion in the postexercise state enhances the synthesis of glutamine and alanine in the skeletal muscle was tested. Glucose was infused intraduodenally for 150 min (44.5 micromol . kg-1 . min-1) beginning 30 min after a 150-min period of exercise (n = 7) or an equivalent duration sedentary period (n = 10) in 18-h-fasted dogs. Prior exercise caused a twofold greater increase in limb glucose uptake during the intraduodenal glucose infusion compared with uptake in sedentary dogs. Arterial glutamine levels fell gradually with the glucose load in both groups. Net hindlimb glutamine efflux increased in response to intraduodenal glucose in exercised but not sedentary dogs (P < 0. 05-0.01). Arterial alanine levels, depleted by 50% with exercise, rose with intraduodenal glucose in exercised but not sedentary dogs (P < 0.05-0.01). Net hindlimb alanine efflux also rose in exercised dogs in response to intraduodenal glucose (P < 0.05-0.01), whereas it was not different from baseline in sedentary controls for the first 90 min of glucose infusion. Beyond this point, it, too, rose significantly. We conclude that oral glucose may facilitate recovery of muscle from prolonged exercise by enhancing the removal of nitrogen in the form of glutamine and alanine.

Alanine↗

PubMed1998

Limitations to exercise- and maximal insulin-stimulated muscle glucose uptake.

The hypothesis of this investigation was that insulin and muscle contraction, by increasing the rate of skeletal muscle glucose transport, would bias control so that glucose delivery to the sarcolemma (and t tubule) and phosphorylation of glucose intracellularly would exert more influence over glucose uptake. Because of the substantial increases in blood flow (and hence glucose delivery) that accompany exercise, we predicted that glucose phosphorylation would become more rate determining during exercise. The transsarcolemmal glucose gradient (TSGG; the glucose concentration difference across the membrane) is inversely related to the degree to which glucose transport determines the rate of glucose uptake. The TSGG was determined by using isotopic methods in conscious rats during euglycemic hyperinsulinemia [Ins; 20 mU/(kg. min); n = 7], during treadmill exercise (Ex, n = 6), and in sedentary, saline-infused rats (Bas, n = 13). Rats received primed, constant intravenous infusions of trace 3-O-[3H]methyl-D-glucose and [U-14C]mannitol. Then 2-deoxy-[3H]glucose was infused for the calculation of a glucose metabolic index (Rg). At the end of experiments, rats were anesthetized, and soleus muscles were excised. Total soleus glucose concentration and the steady-state ratio of intracellular to extracellular 3-O-[3H]methyl-D-glucose (which distributes on the basis of the TSGG) were used to calculate ranges of possible glucose concentrations ([G]) at the inner and outer sarcolemmal surfaces ([G]im and [G]om, respectively). Soleus Rg was increased in Ins and further increased in Ex. In Ins, total soleus glucose, [G]om, and the TSGG were decreased compared with Bas, while [G]im remained near 0. In Ex, total soleus glucose and [G]im were increased compared with Bas, and there was not a decrease in [G]om as was observed in Ins. In addition, accumulation of intracellular free 2-deoxy-[3H]glucose occurred in soleus in both Ex and Ins. Taken together, these data indicate that, in Ex, glucose phosphorylation becomes an important limitation to soleus glucose uptake. In Ins, both glucose delivery and glucose phosphorylation influence the rate of soleus glucose uptake more than under basal conditions.

3-O-Methylglucose↗

PubMed1997

Sympathetic drive to liver and nonhepatic splanchnic tissue during prolonged exercise is increased in diabetes.

This study was conducted to assess whether nonhepatic splanchnic (NHS) and hepatic tissues contribute to the increase in circulating norepinephrine during prolonged exercise, and to determine whether such a response is exaggerated during exercise in the poorly controlled diabetic when the arterial norepinephrine response is excessive. Chronically catheterized (carotid artery, portal vein, and hepatic vein) and instrumented (Doppler flow probes on hepatic artery and portal vein) normal (n = 6) and alloxan-diabetic (n = 5) dogs were studied during rest (30 minutes) and moderate treadmill exercise (150 minutes). Basal plasma glucose of diabetic dogs was threefold that of control dogs. Since epinephrine is not released by splanchnic tissues, NHS and hepatic epinephrine fractional extraction (FX) can be accurately measured. Because epinephrine FX = norepinephrine FX, norepinephrine spillover can be calculated. NHS and hepatic epinephrine FX remained stable during rest and exercise in both control and diabetic dogs. Although basal NHS norepinephrine spillover was not different between the two groups, basal hepatic norepinephrine spillover was lower in the controls (1.1 +/- 0.3 ng/kg . min) compared with the diabetics (3.6 +/- 1.1 ng/kg . min). Although NHS norepinephrine spillover increased with exercise in the normal dog (3.1 +/- 0.6 ng/kg . min at t = 150 minutes), there was no increase in hepatic norepinephrine spillover (1.1 +/- 0.3 ng/kg . min at t = 150 minutes). In contrast, NHS (8.8 +/- 1.6 ng/kg . min at t = 150 minutes) and hepatic (6.9 +/- 1.8 ng/kg . min at t = 150 minutes) norepinephrine spillover were both markedly increased in the diabetic dog to rates approximately threefold and sixfold higher than in the normal dog. These data show that an increase in NHS but not hepatic norepinephrine spillover is a component of the normal response to prolonged exercise. The exaggerated increase in arterial norepinephrine during exercise in the diabetic state is due, in part, to both increased sympathetic drive to the gut and liver. This increase in sympathetic drive to the splanchnic bed may contribute to the deleterious effects of exercise in poorly controlled diabetes.

Animals↗

PubMed1997

Interaction of exercise, insulin, and hypoglycemia studied using euglycemic and hypoglycemic insulin clamps.

Hyperinsulinemic euglycemic and hypoglycemic clamps were used to study the interaction of exercise, insulin, and hypoglycemia at rest and during exercise in the dog. Sampling (artery and portal, hepatic, and iliac veins) and infusion (vena cava) catheters and a flow probe (external iliac artery) were implanted surgically >16 days before study. After an 18-h fast and an 80-min tracer equilibration period, dogs were studied in the basal state (t = -40 to 0 min) and during a moderate treadmill exercise (t = 0-150 min) period or an equivalent duration sedentary period. Insulin was infused at 1 mU x kg(-1) x min(-1) from t = 0-150 min. In one group of sedentary (n = 7) and one group of exercised (n = 6) dogs, glucose was clamped at basal during the insulin infusion. In another group of sedentary (n = 6) and another group of exercised (n = 6) dogs, arterial glucose was clamped at hypoglycemic levels (approximately 65 mg/dl) during the insulin infusion. Arteriovenous difference and isotopic ([3-(3)H]glucose, [U-(14)C]glucose) techniques were used to assess glucose metabolism. Insulin levels were approximately 40 microU/ml in all groups. Data show that 1) counterregulatory hormone (glucagon, catecholamines, and cortisol) responses to exercise and hypoglycemia combined are synergistically higher than the response to either stimulus alone; 2) exercise-induced increases in insulin action are negated during hypoglycemia by the counterregulatory response; 3) decreased need for exogenous glucose during hypoglycemic compared with euglycemic exercise is due to stimulation of endogenous glucose production, which accounts for approximately 30% of the decrease, and reduction of glucose utilization, which accounts for approximately 70%; and 4) insulin-stimulated nonoxidative glucose metabolism is unaffected by exercise or hypoglycemia, whereas insulin-stimulated oxidative glucose metabolism is selectively increased by exercise and decreased by hypoglycemia. In conclusion, the marked rise in insulin action during exercise is matched, under insulin-induced hypoglycemic conditions, by an equally profound increase in counterregulation. The effectiveness of the potent insulin counterregulatory response may be important in decreasing the magnitude and frequency of exercise-induced hypoglycemia.

Animals↗

PubMed1997

Role of hepatic alpha- and beta-adrenergic receptor stimulation on hepatic glucose production during heavy exercise.

The role of catecholamines in the control of hepatic glucose production was studied during heavy exercise in dogs, using a technique to selectively block hepatic alpha- and beta-adrenergic receptors. Surgery was done > 16 days before the study, at which time catheters were implanted in the carotid artery, portal vein, and hepatic vein for sampling and the portal vein and vena cava for infusions. In addition, flow probes were implanted on the portal vein and hepatic artery. Each study consisted of a 100-min equilibration, a 30-min basal, a 20-min heavy exercise (approximately 85% of maximum heart rate), a 30-min recovery, and a 30-min adrenergic blockade test period. Either saline (control; n = 7) or alpha (phentolamine)- and beta (propranolol)-adrenergic blockers (Blk; n = 6) were infused in the portal vein. In both groups, epinephrine (Epi) and norepinephrine (NE) were infused in the portal vein during the blockade test period to create supraphysiological levels at the liver. Isotope ([3-3H]glucose) dilution and arteriovenous differences were used to assess hepatic function. Arterial Epi, NE, glucagon, and insulin levels were similar during exercise in both groups. Endogenous glucose production (Ra) rose similarly during exercise to 7.9 +/- 1.2 and 7.5 +/- 2.0 mg.kg-1.min-1 in control and Blk groups at time = 20 min. Net hepatic glucose output also rose to a similar rate in control and Blk groups with exercise. During the blockade test period, arterial plasma glucose and Ra rose to 164 +/- 5 mg/dl and 12.0 +/- 1.4 mg.kg-1.min-1, respectively, but were essentially unchanged in Blk. The attenuated response to catecholamine infusion in Blk substantiates the effectiveness of the hepatic adrenergic blockade. In conclusion, these results show that direct hepatic adrenergic stimulation does not participate in the increase in Ra, even during the exaggerated sympathetic response to heavy exercise.

Adrenergic alpha-Antagonists↗

PubMed1997

Effect of physical activity and fasting on gut and liver proteolysis in the dog.

The aim of this study was to determine how gut and liver protein kinetics adapt to acute exercise in the 18-h-fasted dog (n = 7) and in dogs glycogen depleted by a 42-h fast (n = 8). For this purpose, sampling (artery and portal and hepatic veins) and infusion (vena cava) catheters and Doppler flow probes (portal vein and hepatic artery) were implanted with animals under general anesthesia. At least 16 days later, an experiment, consisting of a 120-min equilibration period, a 30-min basal sampling period, and a 150-min exercise period, was performed. At the start of the equilibration period, a constant rate infusion of [1-13C]leucine was initiated. Gut and liver leucine appearance and disappearance rates were calculated in these studies by combining a novel stable isotopic method and arteriovenous difference methods. In the determination of tissue leucine kinetics the tissue inflow of both alpha-[13C]ketoisocaproic acid and [13C]leucine was taken into account. The results of this study show that 1) the splanchnic bed (liver plus gut) contributes approximately 40% to the whole body proteolytic rate in the basal state and during exercise in dogs fasted for either 18 or 42 h, 2) the contributions of the gut and liver to splanchnic bed proteolysis is about equal in the basal state in both 18- and 42-h-fasted dogs, and 3) exercise in the 18-h-fasted dog leads to a greater emphasis on gut proteolysis and a lesser emphasis on hepatic proteolysis. These studies highlight the important contribution of gut and hepatic proteolysis to whole body proteolysis and the ability of the gut to acutely adapt to changes in physical activity.

Animals↗

PubMed1997

Sympathetic drive to liver and nonhepatic splanchnic tissue during heavy exercise.

The contribution of sympathetic drive and vascular catecholamine delivery to the splanchnic bed during heavy exercise was studied in dogs that underwent a laparotomy during which flow probes were implanted onto the portal vein and hepatic artery and catheters were inserted into the carotid artery, portal vein, and hepatic vein. At least 16 days after surgery, dogs completed a 20-min heavy exercise protocol (mean work rate of 5.7 +/- 1 miles/h, 20 +/- 2% grade). Arterial epinephrine (Epi) and norepinephrine (NE) increased by approximately 500 and approximately 900 pg/ml, respectively, after 20 min of heavy exercise. Because Epi is not released from the splanchnic bed and because Epi fractional extraction (FX) = NE FX, NE uptake by splanchnic tissue can be calculated despite simultaneous release of NE. Basal nonhepatic splanchnic (NHS) FX increased from a basal rate of 0.52 +/- 0.09 to a peak of 0.64 +/- 0.05 at 10 min of exercise. Hepatic Epi FX increased from a basal rate of 0.68 +/- 0.10 to 0.81 +/- 0.09 at 20 min of exercise. Even though NHS extraction of Epi reduced portal vein Epi levels by approximately 60%, the release of NE from NHS tissue maintained portal vein NE at levels similar to those in arterial blood. NHS NE spillover increased from a basal rate of 5.7 +/- 1.4 to 11.7 +/- 2.8 ng x kg(-1) x min(-1) at 20 min of exercise. Hepatic NE spillover increased from a basal rate of 5.0 +/- 1.2 ng x kg(-1) x min(-1) to a peak of 14.2 +/- 2.8 ng x kg(-1) x min(-1) at 15 min of exercise. These results show that 1) approximately two- and threefold increases in NHS and hepatic NE spillover occur during heavy exercise, demonstrating that sympathetic drive to these tissues contributes to the increase in circulating NE; 2) the high catecholamine FX by the NHS tissues results in an Epi level at the liver that is considerably lower than that in the arterial blood; and 3) circulating NE delivery to the liver is sustained despite high catecholamine FX due to simultaneous NHS NE release.

Animals↗

PubMed1997

Gut and liver fat metabolism in depancreatized dogs: effects of exercise and acute insulin infusion.

Excessive circulating fat levels are a defining feature of poor metabolic control in diabetes. Splanchnic adipose tissue is a source of free fatty acids (FFA), and the liver is a key site of FFA utilization and the sole source of ketones. Despite the role of splanchnic tissues in fat metabolism, little is known about how these tissues respond to diabetes under divergent metabolic conditions. Therefore, splanchnic fat metabolism was studied in poorly controlled diabetes under two conditions. First, it was studied during exercise, a stimulus that enhances FFA flux. Second, it was studied while insulin was being acutely infused to achieve levels normally present during exercise, a treatment that may be expected to inhibit lipolysis. For this purpose, liver and gut arteriovenous differences were used during rest and 2.5 h of treadmill exercise in insulin-deficient (n = 6) and acutely insulin-infused (n = 4) depancreatized (PX) dogs. The data show that 1) exercise, in insulin-deficient PX dogs, leads to an increase in net FFA release from mesenteric fat that is equal in magnitude to the response in nondiabetic dogs; 2) net hepatic fractional FFA extraction is increased twofold during exercise in both insulin-deficient PX dogs and nondiabetic control dogs; 3) during exercise, approximately 40 and 75% of the FFA consumed by the liver is effectively transferred from fat stores mobilized from splanchnic adipose tissue in insulin-deficient PX and nondiabetic dogs, respectively; 4) hepatic ketogenic efficiency is elevated during rest three- to fourfold in insulin-deficient PX dogs compared with nondiabetic control dogs and remains elevated during exercise; and 5) surprisingly, acute insulin replacement is ineffective in normalizing net gut, hepatic, or splanchnic FFA or ketone body balances in PX dogs.

Adipose Tissue↗

PubMed1996

Effect of prior exercise on the partitioning of an intestinal glucose load between splanchnic bed and skeletal muscle.

Exercise leads to marked increases in muscle insulin sensitivity and glucose effectiveness. Oral glucose tolerance immediately after exercise is generally not improved. The hypothesis tested by these experiments is that after exercise the increased muscle glucose uptake during an intestinal glucose load is counterbalanced by an increase in the efficiency with which glucose enters the circulation and that this occurs due to an increase in intestinal glucose absorption or decrease in hepatic glucose disposal. For this purpose, sampling (artery and portal, hepatic, and femoral veins) and infusion (vena cava, duodenum) catheters and Doppler flow probes (portal vein, hepatic artery, external iliac artery) were implanted 17 d before study. Overnightfasted dogs were studied after 150 min of moderate treadmill exercise or an equal duration rest period. Glucose ([14C]glucose labeled) was infused in the duodenum at 8 mg/kg x min for 150 min beginning 30 min after exercise or rest periods. Values, depending on the specific variable, are the mean +/- SE for six to eight dogs. Measurements are from the last 60 min of the intraduodenal glucose infusion. In response to intraduodenal glucose, arterial plasma glucose rose more in exercised (103 +/- 4 to 154 +/- 6 mg/dl) compared with rested (104 +/- 2 to 139 +/- 3 mg/dl) dogs. The greater increase in glucose occurred even though net limb glucose uptake was elevated after exercise (35 +/- 5 vs. 20 +/- 2 mg/min) as net splanchnic glucose output (5.1 +/- 0.8 vs. 2.1 +/- 0.6 mg/kg x min) and systemic appearance of intraduodenal glucose (8.1 +/- 0.6 vs. 6.3 +/- 0.7 mg/kg x min) were also increased due to a higher net gut glucose output (6.1 +/- 0.7 vs. 3.6 +/- 0.9 mg/kg x min). Adaptations at the muscle led to increased net glycogen deposition after exercise [1.4 +/- 0.3 vs. 0.5 +/- 0.1 mg/(gram of tissue x 150 min)], while no such increase in glycogen storage was seen in liver [3.9 +/- 1.0 vs. 4.1 +/- 1.1 mg/(gram of tissue x 150 min) in exercised and sedentary animals, respectively]. These experiments show that the increase in the ability of previously working muscle to store glycogen is not solely a result of changes at the muscle itself, but is also a result of changes in the splanchnic bed that increase the efficiency with which oral glucose is made available in the systemic circulation.

Animals↗

PubMed1996

Gut proteolysis contributes essential amino acids during exercise.

Arteriovenous difference and tracer dilution techniques were utilized to determine the effect of exercise on whole body, gut, liver, and splanchnic leucine kinetics. Five postabsorptive dogs were infused with [1-13C]leucine and studied during rest, 90 min of moderate-intensity treadmill exercise (1st 45 min, early; last 45 min, late exercise), and 90 min of recovery. The whole body leucine rate of appearance (Rai; mumol.min 1.kg-1) increased from rest (3.33 +/- 0.11) during early (3.68 +/- 0.14) and late (4.24 +/- 0.27, P < 0.05) exercise and was 3.41 +/- 0.19 during recovery. Gut Ra increased from rest (0.64 +/- 0.08) during early (0.92 +/- 0.12) and late (1.30 +/- 0.20, P < 0.05) exercise and was 0.77 +/- 0.16 during recovery. Liver leucine Ra did not significantly change (P > 0.05). The whole body leucine rate of disappearance (Rd) paralleled whole body leucine Ra throughout. Leucine Rd across the gut, liver, and splanchnic bed, however, did not significantly change (P > 0.05), indicating an increase in leucine uptake outside of these regions. Because active skeletal muscle is likely the principal consumer of these amino acids, the data suggest that gut protein-derived amino acids are utilized for the attenuation of net muscle protein catabolism during and immediately following exercise.

Amino Acids↗