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D H Wasserman

Publications and source records attributed to D H Wasserman.

At least 19 recordsLinked to original sources
PubMed1995

Regulation of glucose fluxes during exercise in the postabsorptive state.

The increase in glucose utilization by the working muscle would lead to hypoglycemia were it not accompanied by an increase in hepatic glucose production. Although the increase in glucose uptake is normally driven by mechanisms that are primarily independent of the action of insulin and other hormones, the response of the liver appears to be closely controlled by the endocrine system. Although considerable progress has been made in understanding the bases for the increases in glucose utilization and production, the means by which these two processes are coordinated to form the exercise response are unclear (e.g. feedback or central feedforward control). Work intensity affects the mechanisms by which glucose fluxes are regulated. For example, during moderate-intensity exercise, the glucoregulatory response resembles glucoregulation in the basal state in that under both conditions, glucose release from the liver is controlled by glucagon and insulin, and blood glucose levels are tightly controlled. The response to high-intensity exercise, on the other hand, takes on characteristics of the stress response, as described by Cannon (13). That is, the catecholamine response increases disproportionately for a given increment in work intensity, and glucose levels are no longer closely regulated, but increase. The specific factors that turn exercise into stress at higher work intensities are not well defined. Determining factors involved in the regulation of glucose fluxes are limited in some respects because the body is more sensitive than are experimental detection methods to various stimuli (glucose, hormones, neurotransmitter release). More complete delineation of mechanisms involved in the regulation of glucose fluxes will require the development of improved techniques and unique experimental models. The trend in the physiological sciences is for more study at the level of the gene. Technical limitations will be overcome or circumvented as knowledge of gene regulation and the development of genetically engineered animal models provide new avenues with which to address basic questions regarding the control of glucose fluxes during exercise.

Blood Glucose↗
PubMed1995

Contribution of pancreatic hormone responses to the elevation in carbohydrate metabolism with reduced PaO2.

Reduced O2 availability, as might occur under some physiological and pathological conditions, stimulates insulin and glucagon release and increases glucose fluxes and muscle carbohydrate metabolism. The aim of this study was to determine the role of reduced PO2, independent of changes in glucagon and insulin. In six dogs, in paired studies separated by 2 wk, glucagon and insulin levels were fixed throughout by infusion of somatostatin with basal intraportal glucagon and insulin replacement. A control period was followed by 90 min of breathing 21% (NO) or 8% (LO) O2. Isotopic and arteriovenous methods were used to assess carbohydrate metabolism. Measured variables were constant over time in NO. Arterial PO2 (Pao2) was approximately 100 mmHg in NO and approximately 30 mmHg in LO, resulting in a 50% fall in O2 content. Insulin, glucagon, and catecholamine levels were similar in NO and LO. Cortisol was significantly increased in LO. Arterial glucose was unchanged in both groups. In the last 45 min of the experimental period in LO, 1) glucose production (14 +/- 1 to 18 +/- 1 mumol.kg-1.min-1), glucose disappearance (15 +/- 1 to 17 +/- 1 mumol.kg-1.min-1), and net hepatic glucose output (11 +/- 1 to 15 +/- 1 mumol.kg-1.min-1) rose, 2) limb pyruvate oxidation (11 +/- 2 to 24 +/- 5 mumol/min) and estimated glycogenolysis (9 +/- 3 to 42 +/- 9 mumol/min) increased, 3) percentages of CO2 from limb pyruvate and glucose increased, and percentage of lactate from blood glucose decreased, and 4) arterial blood lactate was approximately 100% more, although net limb and hepatic lactate balances were unaltered, which suggests that neither liver nor muscle is the source of increased blood lactate. Comparison of these results with our previous study [Zinker et al. Am. J. Physiol. 266 (Endocrinol. Metab. 29): E921-E929, 1994] shows that the response to reduced PaO2, although present, is reduced when glucagon and insulin levels are fixed at basal. The majority of stimulation of glucose production by decreased PaO2 is still present when pancreatic hormones are clamped at basal, while the response by the hindlimb tissues is greatly reduced.

Animals↗
PubMed1995

Interaction of decreased arterial PO2 and exercise on carbohydrate metabolism in the dog.

To determine the mechanism by which low arterial PO2 (PaO2) affects muscle carbohydrate (CHO) metabolism during exercise, dogs inhaled gas consisting of 0.21 (NO; n = 6) or 0.11 (LO; n = 6) inspired oxygen fraction (FIO2) during rest and 150 min of moderate treadmill exercise. Limb arteriovenous difference and isotopic ([3H]- and [14C]glucose) methods were used to assess muscle carbohydrate metabolism: PaO2 was reduced by approximately 50% in LO vs. NO, but limb O2 uptake was similar. Glucose disappearance was increased during rest (13 +/- 2 vs. 19 +/- 1 mumol.kg-1.min-1) and exercise (23 +/- 4 vs. 36 +/- 6 mumol.kg-1.min-1 at 150 min) in LO vs. NO, but arterial glucose was unchanged because hepatic glucose production was increased similarly. Limb glucose and pyruvate oxidation (derived from vein [14C]lactate specific activity) rates were elevated about twofold during rest and exercise in LO vs. NO. Estimated limb glycogenolysis increased at rest (21 +/- 9 vs. 96 +/- 23 mumol/min) and during exercise (70 +/- 21 vs. 184 +/- 41 mumol/min at 150 min) in LO vs. NO. The %CO2 and %lactate from glucose in LO were about twofold the values in NO in rest and exercise. The %CO2 from pyruvate was greater and free fatty acid levels were lower, suggesting reduced fat metabolism in LO. Arterial lactate and pyruvate levels were elevated during rest and the initial 30 min of exercise, even though net limb outputs were no greater. Lactate-to-pyruvate ratios and pH were similar in LO and NO during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Carbohydrate metabolism during exercise: influence of circulating fat availability.

To examine the role of circulating fat in the regulation of carbohydrate metabolism, dogs were studied during rest and 90 min of moderate treadmill exercise with nicotinic acid infused to suppress lipolysis with (+Fat; n = 5) or without (-Fat; n = 5) Intralipid. Isotopic and hindlimb arteriovenous methods were used to assess metabolism. Plasma glucose was similar in both protocols during rest and exercise. Differences in insulin, catecholamines, and cortisol between groups were insignificant. Glucagon was approximately 50% greater during rest and exercise in -Fat. The following values represent those at 30 or 40 min of muscular work because peak responses were seen at these times. Arterial free fatty acid levels were 1,129 +/- 253 and 272 +/- 17 mu eq/l at rest and 756 +/- 145 and 269 +/- 51 mu eq/l with exercise in +Fat and -Fat, respectively. Glucose production was 4.2 +/- 0.3 and 5.0 +/- 0.4 mg.kg-1.min-1 at rest and 8.5 +/- 1.3 and 11.4 +/- 0.6 mg.kg-1.min-1 with exercise in +Fat and -Fat, respectively. Glucose utilization was 4.3 +/- 0.3 and 5.3 +/- 0.2 mg.kg-1.min-1 at rest and 9.2 +/- 1.2 and 12.7 +/- 0.8 mg.kg-1.min-1 with exercise in +Fat and -Fat, respectively. Significant glucose flux differences were present during rest and exercise. Limb glucose uptake rose similarly with exercise in +Fat (29 +/- 7 to 82 +/- 22 mumol/min) and -Fat (28 +/- 7 to 88 +/- 16 mumol/min). Arterial blood lactate was 50-100% greater in -Fat compared with that in +Fat.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Effects of an acute increase in epinephrine and cortisol on carbohydrate metabolism during insulin deficiency.

This study was undertaken to investigate the effects of an acute increase in the plasma epinephrine level, with or without an accompanying increase in the plasma cortisol level, during selective insulin deficiency on glycogenolysis and gluconeogenesis in conscious overnight-fasted dogs. Experiments consisted of an 80-min tracer and dye equilibration period, a 40-min basal period, and a 180-min experimental period. In all protocols, selective insulin deficiency was created during the experimental period by infusing somatostatin peripherally (0.8 micrograms.kg-1.min-1) with basal replacement of glucagon intraportally (0.65 ng.kg-1.min-1). In EPI+SAL (n = 6), an additional infusion of epinephrine (0.04 micrograms.kg-1.min-1) was infused during the experimental period along with saline. In EPI+CORT (n = 6), hydrocortisone (3.0 microgram.kg-1.min-1) was infused in addition to epinephrine during the experimental period. In SAL+CORT (n = 5), hydrocortisone was infused during the experimental period. In SALINE (n = 5), neither epinephrine nor cortisol was infused. [3-3H]glucose, [U-14C]alanine, and indocyanine green dye were used to assess glucose production (rate of appearance [Ra]) and gluconeogenesis using tracer and arteriovenous difference techniques. During selective insulin deficiency in SALINE, the arterial plasma glucose level increased from 6.0 +/- 0.1 to 15.8 +/- 1.1 mmol/l; Ra increased from 14.7 +/- 0.7 to 24.9 +/- 1.7 mumol.kg-1.min-1. Gluconeogenic efficiency and the conversion of alanine and lactate to glucose increased to 300 +/- 55 and 355 +/- 67% of basal. In EPI+SAL and EPI+CORT, plasma glucose increased from 6.2 +/- 0.1 to 19.8 +/- 0.9 mmol/l and from 6.3 +/- 0.1 to 19.5 +/- 0.9 mmol/l. In EPI+SAL and EPI+CORT, Ra increased from 16.5 +/- 1.1 to 29.3 +/- 3.2 mumol.kg-1.min-1 and from 15.4 +/- 1.3 to 28.3 +/- 2.5 mumol.kg-1.min-1. The rise in gluconeogenic efficiency was similar to the rise that occurred in SALINE, but gluconeogenic conversion increased 17-fold in each of the two epinephrine groups. During the epinephrine infusion, gluconeogenesis accounted for a maximum of 55% of total glucose production as opposed to 31% during insulin deficiency alone. An increase in cortisol alone during insulin deficiency (SAL+CORT) had no effect on glucose level, glucose production, or gluconeogenesis. These results suggest that small increases in the plasma epinephrine level during insulin deficiency can significantly worsen the resulting hyperglycemia through stimulation of both glycogenolysis and gluconeogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)

Alanine↗
PubMed1995

Role of the endocrine pancreas in control of fuel metabolism by the liver during exercise.

The secretions of the pancreas drain into the portal vein just upstream of the liver. This anatomical arrangement is an important component of hepatic function since the pancreatic hormones are key regulators of intermediary metabolism in the liver. In response to moderate-intensity exercise, the secretion of glucagon and insulin from the pancreas generally increase and decrease, respectively. This element of the endocrine response to exercise is critical to the maintenance of glucose homeostasis during exercise. The rise in glucagon and fall in insulin are important for the stimulation of hepatic glycogenolysis. The glucagon response is essential for the exercise-induced increase in gluconeogenesis. In addition, glucagon and insulin are also important to the increase in hepatic fat oxidation during exercise. The fall in insulin enhances the mobilization of NEFA's from adipose tissue and as a result the availability of NEFA's to the liver. The increase in glucagon enhances the oxidation of these NEFA's by stimulating pathways for fat oxidation inside the liver. Hepatic fractional amino acid extraction is increased by glucagon action during exercise. Moreover, the increase in glucagon facilitates the channeling of amino acid carbons to glucose and may play a role in disposal of associated nitrogen. Because of the important roles that glucagon and insulin play, any physiological or pathological condition that affects their secretion or efficacy will impact on the metabolic response to exercise.

Amino Acids↗
PubMed1994

Impact of suprapharmacological androgenic steroid administration on basal and insulin-stimulated glucose and amino acid metabolism.

Effects of androgenic steroids at doses used by athletes were studied in a canine model system in which dosage, diet, and activity were controlled. Dogs were treated with 19-nortestosterone (200 mg/wk intramuscularly) or vehicle and were studied at 18 (n = 4 in steroid and vehicle) or 32 (n = 6 in steroid and n = 4 in vehicle) days. A laparotomy was performed under general anesthesia 17 days before experimentation, and catheters were placed in an artery, portal vein, and hepatic vein. Studies consisted of an equilibration (120 minutes) and a control (40 minutes) period and a three-step immunoreactive insulin euglycemic clamp (1, 2, and 15 mU/kg.min). Step 1 was 150 minutes, and steps 2 and 3 were 90 minutes. Data were collected during the last 30 minutes of each step. Glucose and leucine kinetics were assessed with 3H-glucose and 14C-leucine. Plasma glucose in steroid and vehicle groups was 104 +/- 5 (mean +/- SE) versus 108 +/- 3 mg/dL and 100 +/- 5 versus 107 +/- 4 mg/dL at 18 and 32 days. Glucose turnover was similar at 18 days in steroid and vehicle groups (3.9 +/- 0.3 v 3.6 +/- 0.3 mg/kg.min, respectively), but was elevated in the steroid group at 32 days (5.4 +/- 0.5 v 3.2 +/- 0.4 mg/kg.min). Glucose infusion rates were lower in the steroid group with 15 mU/kg.min immunoreactive insulin at 32 days (15.0 +/- 1.1 v 21.2 +/- 1.4 mU/kg.min). Immunoreactive insulin-independent glucose utilization (Rd) was unaffected at 18 days of steroid treatment, but was increased by almost fourfold at 32 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1994

The effects of acute hypercortisolemia on beta-hydroxybutyrate and glycerol metabolism during insulin deficiency.

The present study was undertaken to determine whether an acute physiologic rise in plasma cortisol during selective insulin deficiency would have significant effects on glycerol and beta-hydroxybutyrate metabolism in conscious overnight-fasted dogs. Each experiment consisted of a two hour dye equilibration period, a 40 minute basal period, and a 3 hour experimental period. A continuous infusion of indocyanine green dye for blood flow estimation was initiated at the start of the equilibration period and continued throughout the experiment. In both of two protocols selective insulin deficiency was created during the experimental period by infusing somatostatin peripherally (0.8 microgram/kg-min) with basal replacement of glucagon intraportally (0.65 ng/kg-min). In the test protocol (CORTISOL, n = 5), 3.0 micrograms/kg-min of hydrocortisone was infused during the experimental period. In the control protocol (SALINE, n = 5), saline was infused. Net hepatic balances were determined using the (A-V) difference technique. During selective insulin deficiency alone (SALINE), the arterial blood glycerol level increased from 81 +/- 19 to 140 +/- 11 microM (p < 0.01) and net hepatic glycerol uptake (NHGlyU) tended to increase from 2.3 +/- 0.3 to 3.3 +/- 0.6 mumol/kg-min (0.05 < 0.1). The arterial plasma free fatty acid (FFA) level remained unchanged at 1041 +/- 35 microM. The arterial beta-hydroxybutyrate (BHOB) level increased slightly from 21 +/- 4 to 29 +/- 5 microM while net hepatic beta-hydroxybutyrate production (NHBP) remained unchanged (1.0 +/- 0.2 mumol/kg-min). During acute hypercortisolemia with selective insulin deficiency (CORTISOL), similar changes occurred in the arterial blood glycerol level and net hepatic glycerol uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1994

Rat skeletal muscle hexokinase II mRNA and activity are increased by a single bout of acute exercise.

This study addresses the potential role of skeletal muscle hexokinase (HK) II in the regulation of glucose uptake and metabolism in vivo. Male rats undertook a single bout of treadmill exercise and were then killed immediately or after a predetermined recovery period. Three muscles [soleus (Sol), gastrocnemius/plantaris (Gc), and white vastus] were excised, and HK II mRNA, GLUT-4 mRNA, total HK (HK I and HK II) and heat-stable HK (predominantly HK I) activities were assessed. Three hours after the cessation of a single bout of exhaustive exercise, HK II mRNA was significantly increased in all three muscles. Ninety or thirty minutes of exercise, with a 3-h recovery, increased Gc HK II mRNA to the same extent as exhaustive exercise, but 15 min of exercise had no effect. Gc HK II mRNA continued to increase up to 8 h after the cessation of 90 min of exercise but returned to basal by 24 h postexercise. In contrast to HK II mRNA, Gc GLUT-4 mRNA was unchanged at 0, 3, 8, and 24 h after the cessation of 90 min of exercise. Total HK activity was significantly increased in Sol and Gc, 8 and 24 h after the cessation of 90 min of exercise. Heat-stable HK activity was unchanged in all three muscles. The increase in total HK activity, inferred to be an increase of HK II, may be important in the persistence of the postexercise increase in insulin action.

Animals↗
PubMed1994

Effects of chronic hypercortisolemia on carbohydrate metabolism during insulin deficiency.

This study was undertaken to further investigate the effect of acute selective insulin deficiency on glycogenolysis and gluconeogenesis occurring during chronic physiological hypercortisolemia in conscious overnight fasted dogs. After an 80-min tracer and dye equilibration period and a 40-min basal period, selective insulin deficiency was created during the 180-min experimental period by infusing somatostatin peripherally (0.8 micrograms.kg-1.min-1) with basal replacement of glucagon intraportally (0.65 ng.kg-1.min-1). In the cortisol group (n = 5), a continuous infusion of hydrocortisone (3.5 micrograms.kg-1.min-1) was begun 5 days before the experiment. In the saline group (n = 5), there was no infusion of cortisol. [3-3H]glucose, [U-14C]alanine, and indocyanine green dye were used to assess glucose production and gluconeogenesis using tracer and arteriovenous difference techniques. During selective insulin deficiency in the saline group, the arterial plasma glucose level (Glc) increased from 109 +/- 2 to 285 +/- 19 mg/dl; glucose production increased from 2.7 +/- 0.2 to 4.5 +/- 0.3 mg.kg-1.min-1. Gluconeogenic efficiency and conversion of alanine to glucose (Conv) increased by 300 +/- 55 and 356 +/- 67%. During selective insulin deficiency in the cortisol group, Glc increased from 117 +/- 3 to 373 +/- 50 mg/dl; glucose production increased from 3.3 +/- 0.5 to 6.9 +/- 0.7 mg.kg-1.min-1. Gluconeogenic efficiency and Conv increased by 268 +/- 41 and 393 +/- 75%, respectively. The maximal glycogenolytic rate increased significantly more in the cortisol group than in the saline group, accounting for the difference in glucose production. These results suggest that, even during chronic hypercortisolemia, acute insulin deficiency has more pronounced effects on glycogenolysis than gluconeogenesis.

Alanine↗
PubMed1994

Exercise-induced fall in insulin: mechanism of action at the liver and effects on muscle glucose metabolism.

To determine the importance of the fall in insulin on whole body glucose fluxes and muscle glucose metabolism during exercise, dogs ran on a motorized treadmill for 90 min at a moderate work rate with somatostatin (SRIF) infused to suppress insulin and glucagon and basal (B-INS; n = 6 dogs) or exercise-stimulated (S-INS; n = 8 dogs) insulin replacement. The fall in insulin during exercise potently stimulates glucose production at least in part by potentiating the actions of glucagon. To assess the hepatic effects of insulin in the absence of its potentiating effect on glucagon action, glucagon levels were not restored during SRIF infusion. At least 17 days before experimentation, dogs underwent surgery for chronic placement of sampling (carotid artery and femoral vein) and infusion (inferior vena cava and portal vein) catheters. Hindlimb blood flow was assessed by placement of a Doppler flow cuff on the external iliac artery. Whole body glucose production (Ra) and disappearance (Rd) were assessed with [3-3H]glucose, and hindlimb glucose uptake and metabolism were assessed with arterial-venous differences and [U-14C]glucose. Insulin levels were 69 +/- 6 and 61 +/- 7 pM at rest in B-INS and S-INS and 62 +/- 10 and 41 +/- 6 pM at 30 min of exercise. Glucose levels were clamped at euglycemic levels with an exogenous glucose infusion during rest and exercise in both groups. Exercise-induced increases in Ra, Rd, hindlimb glucose uptake, and hindlimb oxidative and nonoxidative glucose metabolism were not affected by maintenance of basil insulin levels during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗
PubMed1994

Acute adaptation of carbohydrate metabolism to decreased arterial PO2.

To assess the interaction of arterial PO2 (PaO2) and glucose metabolism, conscious 18-h-fasted dogs with chronically implanted sampling catheters (carotid artery, iliac vein) and flow probe (external iliac artery) were studied during inspiration of air containing 21 (n = 9), 14 (n = 6), 11 (n = 4), or 8% (n = 5) O2. Isotopic and arteriovenous methods were used to assess carbohydrate metabolism. PaO2 was 103 +/- 3, 64 +/- 4, 45 +/- 4, and 30 +/- 1 mmHg with decreased inspired O2. Although limb O2 delivery was reduced (51 +/- 6, 42 +/- 8, 39 +/- 7, and 34 +/- 5 ml/min), limb O2 uptake was not compromised. Plasma insulin was 9 +/- 1, 8 +/- 2, 14 +/- 2, and 16 +/- 3 microU/ml, and glucagon was 53 +/- 3, 49 +/- 3, 64 +/- 5, and 101 +/- 7 pg/ml with decreasing O2. Plasma epinephrine and cortisol were increased whereas norepinephrine was unaffected. Glycemia was unaffected by reduced O2, whereas hepatic glucose output (14 +/- 1, 19 +/- 3, 21 +/- 1, and 22 +/- 1 mumol.kg-1.min-1) and glucose disappearance (14 +/- 2, 18 +/- 3, 20 +/- 1, and 22 +/- 2 mumol.kg-1.min-1) rose similarly. Limb glucose uptake (LGU) rose (21.5 +/- 4.7, 21.2 +/- 5.6, 30.6 +/- 4.7, and 45.3 +/- 9.7 mumol/min) with decreasing O2 because of greater fractional extraction (0.023 +/- 0.005, 0.024 +/- 0.005, 0.031 +/- 0.004, and 0.043 +/- 0.004). Of the increased LGU, approximately 33 and 67% were metabolized oxidatively and nonoxidatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1994

Sensitivity of exercise-induced increase in hepatic glucose production to glucose supply and demand.

It was hypothesized that the exercise-induced changes in glucoregulatory hormones and glucose production (Ra) occur as a result of a small deficit in glucose availability. To test this, 18-h fasted dogs performed 150 min of treadmill exercise with either the liver as the sole source of glucose (controls, n = 5) or with glucose infused from 0 to 50 min (period 1) and from 100 to 150 min (period 3) at rates designed to track the glucose utilization (Rd) response (ExoGlc, n = 5). The liver alone supplied glucose from 50 to 100 min (period 2). Isotopic and arteriovenous methods were used to assess Ra, Rd, and gluconeogenesis (GNG). Variable [3H]glucose infusion and frequent sampling were used to facilitate Ra measurements. Arterial glucose declined by -3.1 +/- 1.4, -4.3 +/- 2.9, and -6.4 +/- 3.7 mg/dl in periods 1-3 in controls (changes are mean values during each of the 50-min periods; P < 0.05). In ExoGlc, arterial glucose did not deviate from basal in periods 1 (+0.1 +/- 1.8 mg/dl) and 3 (+1.5 +/- 4.5 mg/dl) but fell from basal (P < 0.05) by the same amount as controls in period 2 (-5.7 +/- 2.1 mg/dl). Matching the Rd response with exogenous glucose led to increases in arterial and portal vein plasma insulin levels (P < 0.05) but did not affect glucagon, norepinephrine, epinephrine, and cortisol levels. Ra was elevated by 3.1 +/- 0.5, 4.0 +/- 1.1, and 4.7 +/- 1.1 mg.kg-1.min-1 in periods 1-3 in controls (P < 0.05). In ExoGlc, Ra rose by 0.0 +/- 0.4, 4.1 +/- 1.4 (P < 0.05), and 0.4 +/- 0.7 mg.kg-1.min-1, respectively, in periods 1-3. The rise in Ra was reduced in periods 1 and 3 of ExoGlc compared with controls (P < 0.02). GNG rose to approximately 250% basal in controls and did not respond with any significant difference in ExoGlc. In summary, the exercise-induced increases in counterregulatory hormones and GNG are present even when a deficit in glucose supply is eliminated by an exogenous glucose infusion. In contrast, the fall in insulin and the rise in hepatic glycogenolysis are greatly attenuated. The regulatory components affected by exogenous glucose predominate at the liver as deviations in plasma glucose of approximately 4% correspond to approximately 60% changes in Ra.(ABSTRACT TRUNCATED AT 400 WORDS)

Alanine↗
PubMed1993

The effects of lactate loading on alanine and glucose metabolism in the conscious dog.

The effect of lactate per se on alanine and glucose metabolism was studied in five overnight-fasted conscious dogs. Somatostatin was infused to inhibit endogenous pancreatic insulin and glucagon release and the hormones were replaced intraportally at basal rates. Saline (n = 5) or lactate (at 25 and 50 mumol.kg-1.min-1 for 90 minutes each) was infused, and blood samples were taken during the last 30 minutes of each 90-minute period. Insulin, epinephrine, norepinephrine, and cortisol levels remained unchanged during saline or lactate infusion. Glucagon level decreased slightly during lactate (94 +/- 7 to 74 +/- 9 and 79 +/- 8 pg/mL) and saline (91 +/- 8 to 90 +/- 4 and 81 +/- 11 pg/mL) infusions. There were no significant changes in lactate or alanine levels or net hepatic balances with saline infusion. Blood lactate level increased from 657 +/- 74 to 1,718 +/- 126 and 3,300 +/- 321 mumol/L (both P < .05) during the low- and high-lactate infusion periods, respectively. The liver produced lactate during the control (5.57 +/- 2.92 mumol.kg-1 x min-1) and low-lactate infusion (1.75 +/- 2.58 mumol.kg-1 x min-1) periods, but consumed lactate (3.89 +/- 3.31 mumol.kg-1 x min -1; P < .05) during the high-lactate infusion period.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗
PubMed1993

Hepatic denervation alters the transition from the fed to the food-deprived state in conscious dogs.

The hepatic nerves can modulate hepatic glycogenolysis and glycogenesis and thus might be expected to be involved in the response of the animal to the transition from the fed to the food-deprived state. Therefore the arterial concentrations and net hepatic balance of glucose and its metabolites, as well as the hepatic glycogen concentrations, were compared in hepatic-innervated and -denervated dogs 18, 24 and 42 h after their usual daily meal. Arterial concentrations of glucose, alanine, lactate and glycerol; net hepatic balances of glucose, alanine and glycerol; and glycogen concentrations were similar in hepatic-innervated and -denervated dogs at each time investigated. Net hepatic balances of lactate (with negative values indicating uptake) in hepatic-innervated and -denervated dogs, respectively, were: 18 h, 4.1 +/- 4.3 vs. -4.3 +/- 3.6 mumol.kg-1 x min-1; 24 h, 4.8 +/- 3.6 vs. -6.7 +/- 1.7 mumol.kg-1 x min-1 (P < 0.05); 42 h, -7.0 +/- 2.0 vs. -6.8 +/- 1.0 mumol.kg-1 x min-1. Based on changes in net hepatic lactate balance, the denervated liver responds more rapidly to food deprivation than the innervated liver, but the metabolic state of the liver appears similar by 42 h after a meal.

Alanine↗
PubMed1993

Effects of chronic elevation in plasma cortisol on hepatic carbohydrate metabolism.

This study was undertaken to investigate the effects of chronic physiological elevations in plasma cortisol on glycogenolysis and gluconeogenesis in conscious, overnight-fasted dogs. Experiments consisted of an 80-min tracer and dye equilibration period and a 40-min sampling period. Infusions of D-[3-3H]glucose, L-[U-14C]alanine, and indocyanine green dye were used to assess glucose production (Ra) and gluconeogenesis using tracer and arteriovenous (a-v) difference techniques. In the cortisol group, (n = 10), a continuous infusion of hydrocortisone (3.5 micrograms.kg-1 x min-1) was begun 5 days before the experiment and continued throughout the sampling period. In the saline group (n = 10), there was no infusion of cortisol. The fivefold elevation in plasma cortisol increased plasma insulin from 12 +/- 2 to 19 +/- 2 microU/ml. Glucose Ra was elevated in the cortisol group (3.5 +/- 0.2 vs. 2.8 +/- 0.2 mg.kg-1 x min-1) but net hepatic glucose output was markedly diminished (1.2 +/- 0.4 vs. 2.7 +/- 0.3 mg.kg-1 x min-1). Gluconeogenic conversion of alanine to glucose was increased slightly by cortisol (0.60 +/- 0.13 to 0.99 +/- 0.12 mumol.kg-1 x min-1), but the gluconeogenic efficiency of the liver was unchanged. Cortisol increased hepatic glycogen content evident at the end of the study greater than twofold (76.4 +/- 7.9 vs. 30.0 +/- 4.7 g/liver). These results suggest that cortisol 1) promotes glucose cycling through glycogen, 2) greatly inhibits nonhepatic glucose utilization, 3) increases hepatic gluconeogenesis in vivo primarily through enhanced substrate delivery to the liver, and 4) raises plasma insulin levels, which restrains intrahepatic gluconeogenesis.

3-Hydroxybutyric Acid↗