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Biomedical subjects

P Felig

Publications and source records attributed to P Felig.

At least 37 records · Page 2Linked to original sources
PubMed1984

Turnover and splanchnic metabolism of free fatty acids and ketones in insulin-dependent diabetics at rest and in response to exercise.

Nine insulin-dependent diabetics and six healthy controls were studied at rest, during, and after 60 min of bicycle exercise at a work load corresponding to 45% of their maximal oxygen intake. The catheter technique was employed to determine splanchnic and leg exchange of metabolites. FFA turnover and regional exchange was evaluated using [14C]oleate infusion. Basal glucose (13.8 +/- 1.1 mmol/l), ketone body (1.12 +/- 0.12 mmol/l), and FFA (967 +/- 110 mumol/l) concentrations were elevated in the diabetics in comparison with controls. In the resting state, splanchnic ketone acid production in the diabetics was 6-10-fold greater than in controls. Uptake of oleic acid by the splanchnic bed was increased 2-3-fold, and the proportion of splanchnic FFA uptake converted to ketones (61%) was threefold greater than in controls. In contrast, splanchnic fractional extraction of oleic acid was identical in diabetics and controls. A direct relationship was observed between splanchnic uptake and splanchnic inflow (plasma concentration X hepatic plasma flow) of oleic acid that could be described by the same regression line in the diabetic and control groups. During exercise, splanchnic ketone production rose in both groups. In the control group the increase in ketogenesis was associated with a rise in splanchnic inflow and in uptake of oleic acid, a rise in splanchnic fractional extraction of oleate, and an increase in the proportion of splanchnic FFA uptake converted to ketone acids from 20-40%. In the diabetic group, the increase in ketogenesis occurred in the absence of a rise in splanchnic inflow or uptake of oleic acid, but was associated with an increase in splanchnic fractional extraction of oleic acid and a marked increase in hepatic conversion of FFA to ketones, so that the entire uptake of FFA was accountable as ketone acid output. Splanchnic uptake of oleic acid correlated directly with splanchnic oleic acid inflow in both groups, but the slope of the regression line was steeper than in the resting state. Plasma glucagon levels were higher in the diabetic group at rest and during exercise, while plasma norepinephrine showed a twofold greater increment in response to exercise in the diabetic group (to 1,400-1,500 pg/ml). A net uptake of ketone acids by the leg was observed during exercise but could account for less than 5% of leg oxidative metabolism in the diabetics and less than 1% in controls. Despite the increase in ketogenesis during exercise, a rise in arterial ketone acid levels was not observed in the diabetics until postexercise recovery, during which sustained increments to values of 1.8-1.9 mmol/l and sustained increases in splanchnic ketone production were observed at 30-60 min. The largest increment in blood ketone acids and in splanchnic ketone production above values observed in controls thus occurred in the diabetics after 60 min of recovery from exercise. We concluded that: (a) In the resting state, increased ketogenesis in the diabetic is a consequence of augmented splanchnic inflow of FFA and increased intrahepatic conversion of FFA to ketones, but does not depend on augmented fractional extraction of circulating FFA by the splanchnic bed. (b) Exercise-induced increases in ketogenesis in normal subjects are due to augmented splanchnic inflow and fractional extraction of FFA as well as increased intrahepatic conversion of FFA to ketones. (c) When exercise and diabetes are combined, ketogenesis increases further despite the absence of a rise in splanchnic inflow of FFA. An increase in splanchnic fractional extraction of FFA and a marked increase intrahepatic conversion of FFA to ketones accounts for the exaggerated ketogenic response to exercise in the diabetic. (d) Elevated levels of plasma glucagon and/or norepinephrine may account for the increased hepatic ketogenic response to exercise in the diabetic. (e) Ketone utilization by muscle increases during exercise but constitutes a quantitatively minor oxidative fuel for muscle even in the diabetic. (f) The accelerated ketogenesis during exercise in the diabetic continues unabated during the recovery period, resulting in an exaggerated postexercise ketosis.

Adult↗
PubMed1984

Self-monitoring of blood glucose levels in diabetes. Principles and practice.

Self-monitoring of blood glucose levels has become popular due to the limitations in the use of urine testing for assessing the status of diabetes control. Furthermore, the recent emphasis on the importance of diabetes regulation entails that patients tailor the insulin doses based on blood glucose levels. This review discusses the methodology of capillary blood glucose monitoring and its application to insulin adjustments. When performed properly, self-monitoring is accurate, reliable, and effective. It can also be beneficial in detecting hypoglycemia and may have a positive psychological impact as well. The reduction in the frequency of office and laboratory visits makes self-monitoring potentially cost-effective. Although useful for a broad segment of the type I diabetic population and for an increasingly large number of individuals with type II diabetes, self-monitoring may have a limited role in patients with severe, irreversible complications.

Blood Glucose↗
PubMed1984

Insulin pump therapy improves blood glucose control during hyperalimentation.

The present study investigated the feasibility of basal continuous subcutaneous insulin infusion (CSII) in four patients with postoperative sepsis or extensive burns during continuous enteral hyperalimentation with 2,500 to 3,000 calories/day, containing approximately 390 g of simple carbohydrates. The mean duration of CSII treatment was 16.8 days (range, seven to 32 days). The mean capillary blood glucose level fell from 322 +/- 52 mg/dL during pre-CSII therapy to 195 +/- 33 mg/dL during CSII therapy. Only 1.3% of 1,254 capillary blood glucose values were less than 60 mg/dL. Most values (61.6%) were between 61 and 200 mg/dL. The mean insulin infusion rate was 2.5 +/- 1.5 units/hr. These preliminary observations suggest that basal infusion CSII is a safe and effective means of improving blood glucose control in patients receiving enteral hyperalimentation despite the high glucose intake and presence of insulin resistance. Thus, CSII therapy can enhance the metabolic response to hyperalimentation without requiring an intravenous access route.

Blood Glucose↗
PubMed1984

Fuel-hormone metabolism during exercise and after physical training.

In this review the metabolic changes encountered in response to exercise in normal humans are considered in the context of the following categories: (1) fuel utilization and production, (2) hormone secretion, (3) the post-exercise recovery period, (4) effects of physical training on fuels and hormone secretion, and (5) effects of exercise on lipoprotein metabolism.

Carbohydrate Metabolism↗
PubMed1983

Leucine uptake by splanchnic and leg tissues in man: relative independence of insulin levels.

The influence on leucine disposal of physiological alterations in plasma insulin concentrations was examined in three groups of healthy male subjects, six in each group. After an overnight fast the subjects received an intravenous infusion of either leucine (300 mumol/min for 150 min, series A), or leucine plus glucose (2.2 mmol/min, series B), or leucine, somatostatin (7 micrograms/min) and glucagon (1 ng/min, series C). Arterial concentrations of substrates and their net exchange across the splanchnic and leg tissues were determined with a catheter technique. Insulin concentrations rose from 12 +/- 2 to 20-22 mu-units/ml in series A, from 11 +/- 3 to 60-65 65 mu-units/ml in series B and decreased from 8 +/- 1 to approximately 5 mu-units/ml in series C. The basal leucine concentration for all subjects was 109 +/- 8 mumol/l and it rose progressively during the infusions. In series A, the level was 598 +/- 20 mumol/l after 150 min. The corresponding value was 542 +/- 38 mumol/l in series B and 651 +/- 25 mumol/l in series C. Significant differences were observed between series A and B (P less than 0.05) and series A and C (P less than 0.01) when data for 90-150 min of infusion were combined (analysis of variance). In all groups the leucine infusion resulted in an augmented net uptake of leucine across the leg (77-85 mumol/min) and across the splanchnic bed (61-72 mumol/min) but no significant intergroup differences were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Energy expenditure in obesity in fasting and postprandial state.

Resting metabolic rate (RMR) was determined in 10 obese and 10 nonobese women after an overnight fast and for 3 h after the ingestion of an 800-kcal liquid meal. In the fasting state, absolute energy expenditure in the obese (4.8 +/- 0.2 kJ/min) was 25% greater than in the nonobese (P less than 0.005), but was comparable with the nonobese when expressed in relation to body surface area or lean body mass and was reduced by 20% when expressed per kilogram body weight3/4 (P less than 0.005). Meal ingestion resulted in a 14-16% increase in RMR (postprandial thermogenesis) that was similar in the two groups, so that absolute energy expenditure in the obese remained 22-25% higher than in the nonobese throughout the postprandial period. The estimated overall (fasting and postprandial) increase in resting caloric expenditure in the obese as compared with the nonobese was 350-375 kcal/day.

Adult↗
PubMed1983

Splanchnic and renal metabolism of insulin in human subjects: a dose-response study.

Kinetic analyses of insulin metabolism were performed in 32 healthy subjects with hepatic-venous or renal-venous catheters, in whom steady-state conditions of hyperinsulinemia or hyperglycemia were achieved with the use of the glucose-insulin clamp technique. In the basal state, the splanchnic bed removed 42 +/- 2% of the insulin influx. After graded insulin infusions with maintenance of euglycemia, stable arterial insulin levels of 35-1,430 microU/ml were attained. Splanchnic insulin extraction was constant (approximately 60%) at physiological insulin levels but fell (to 29 +/- 1%, P less than 0.02) at supraphysiological (greater than 500 microU/ml) concentrations. The metabolic clearance rate of infused insulin was essentially constant within the physiological concentration range. Hyperglycemia (+125 mg/100 ml) did not alter splanchnic insulin extraction. Basally, the kidneys extracted 0.04 +/- 0.01 mU X min-1 X kg-1 or 25 +/- 5% of arterial insulin. Renal insulin clearance (3.9 +/- 0.4 ml X min-1 X kg-1) represented over 80% of the extrasplanchnic insulin clearance. Hyperglycemia (+125 mg/100 ml) had no effect on renal insulin extraction. In conclusion, a) both splanchnic and renal insulin removal are independent of glycemia and increase in proportion to plasma insulin concentration within the physiological range; b) splanchnic uptake is the dominant mechanism of removal of insulin from the circulation whether the route of delivery is portal or peripheral; and c) the kidneys account for the greater part of extrasplanchnic insulin metabolism.

Adult↗
PubMed1983

Increased efficiency of weight gain and altered cellularity of brown adipose tissue in rats with impaired glucose tolerance during diet-induced overfeeding.

We examined the relationship among glucose tolerance, efficiency of weight gain, and cellularity of brown adipose tissue (BAT) in rats (initial weight: 362 +/- 1 g) made hyperphagic and obese by feeding on a highly palatable "cafeteria" (CAF) diet for 4-8 wk. As compared with chow-fed controls, CAF feeding resulted in a 45-60% increase in caloric intake (P less than 0.01), a 40-50% increase in weight gain (P less than 0.01), and hyperinsulinemia. Glucose disposal rate (K) on intravenous glucose tolerance test (IVGTT) was greater than or equal to 1.4% in all chow-fed rats, but fell to less than or equal to 1.3 in 10 of 23 CAF-fed rats. As compared with the chow-fed controls, rats with normal glucose tolerance demonstrated a 12% decline in efficiency of weight gain (g/100 kcal of food consumed) in response to CAF feeding (P less than 0.05). In marked contrast, in rats with impaired glucose tolerance, efficiency of weight gain failed to decline in response to overfeeding and was 18% higher than in the overfed group with normal glucose tolerance (P less than 0.01). Although CAF feeding increased the mass of interscapular BAT by 110-130% in rats with normal as well as impaired glucose tolerance, DNA content of BAT rose only in the normal-K CAF-fed rats (0.19 +/- 0.01 mg DNA/100 mg versus 0.12 +/- 0.02 in chow-fed controls and 0.12 +/- 0.01 in low-K rats).(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue, Brown↗
PubMed1983

3-O-methyl-D-glucose uptake in isolated rat hepatocytes. Effects of dexamethasone.

We examined the uptake of 3-O-methyl-D-glucose, a nonmetabolizable hexose, by isolated rat hepatocytes. The uptake of 3-O-methyl-D-glucose was linear for 1 min at 22 degrees, and Lineweaver-Burk analysis demonstrated an apparent Km of approximately 6 mM. Cytochalasin B (40 microM) and phloridzin (2 mM) inhibited 3-O-methyl-D-glucose uptake by 88% and 63%, respectively. D-Glucose (20 mM) inhibited the initial rate of 3-O-methyl-D-glucose uptake by 55% (p less than 0.001), whereas L-glucose was without any significant effect. The uptake of 3-O-methyl-D-glucose remained unchanged in the presence of Na+ (0-150 mM) in the incubation medium. After 30 min dexamethasone inhibited glucose uptake (the maximal effect being achieved in a time- and concentration-dependent manner) at 2 microM and 0.5 microM concentrations by 50% and 25%, respectively. Dexamethasone produced a decrease in the Vmax but did not change the Km. Insulin, glucagon, gastric inhibitory polypeptides, and pancreozymin had no effect on 3-O-methyl-D-glucose uptake in isolated hepatocytes. These findings are consistent with the conclusion that 3-O-methyl-D-glucose uptake in isolated rat hepatocytes occurs via a stereospecific, carrier-mediated, facilitated diffusion process. Dexamethasone decreases this process of facilitated diffusion in the isolated hepatocyte.

3-O-Methylglucose↗
PubMed1982

Hypernatremia induced by maximal exercise.

A short burst of intensive exercise (100-m swim lasting one minute and resulting in a 12-fold rise in the level of blood lactate) resulted in frank hypernatremia (serum sodium level, greater than 150 mEq/L) in 30% to 40% of well-trained athletes. In contrast, less intensive exercise (800-m swim lasting ten minutes and resulting in a sevenfold rise in the level of blood lactate) failed to cause a rise in serum sodium level despite comparable elevations in hematocrit reading and serum protein levels. Hypernatremia induced by intensive exercise cannot be explained by losses in body fluid or solute ingestion, but is probably a consequence of a shift of hypotonic fluid from the extracellular to the intracellular compartment. Thus, the mechanism of exercise-induced hypernatremia may be unique, as compared with other clinically recognized forms of hypernatremia.

Adolescent↗
PubMed1982

Hypoglycemia during prolonged exercise in normal men.

Hypoglycemia (blood glucose less than 45 mg per deciliter [less than 2.5 mmol per liter]) occurred in seven of 19 healthy men who exercised to exhaustion on a cycle ergometer at 60 to 65 per cent of maximal aerobic power. The hypoglycemic subjects exercised for 15 to 70 minutes despite blood glucose levels of 25 to 48 mg per deciliter (1.4 to 2.7 mmol per liter), and their exhaustion time (mean +/- S.E.M., 142 +/- 15 minutes) was not significantly different from that of the euglycemic group (165 +/- 11). Plasma epinephrine was inversely related to blood glucose (P less than 0.01) and was three times higher in the hypoglycemic subjects (P less than 0.05). Glucose ingestion (40 or 80 g per hour) prevented the hypoglycemia and resulted in a smaller rise in plasma epinephrine but did not alter perceived exertion or consistently delay exhaustion. We conclude that hypoglycemia occurs in normal subjects during prolonged exercise and results in an exaggerated rise in plasma epinephrine. However, hypoglycemia fails to effect endurance, and its prevention does not consistently delay exhaustion.

Adolescent↗
PubMed1982

Urinary 3-methylhistidine excretion in juvenile-onset diabetics: evidence of increased protein catabolism in the absence of ketoacidosis.

Urinary 3-methylhistidine excretion (an indicator of protein catabolism) was measured in ten diabetic patients and in age and weight matched control subjects. The diabetic group, while receiving their usual insulin dose, excreted 42% more 3-methylhistidine than the control group (2.7 versus 1.9 mumole/kg body weight/24 hr). When the insulin dose of the diabetic subject was reduced by 15% or 25%, the concentrations of blood and urinary glucose were significantly increased by the rate of urinary 3-methylhistidine excretion was not increased further. These findings demonstrate augmented protein catabolism in diabetics even in the absence of ketoacidosis. It appears that blood and urine glucose levels are more sensitive to changes in insulin availability than protein catabolism.

Adult↗
PubMed1982

Influence of physical training on the fuel-hormone response to prolonged low intensity exercise.

The effects of physical training on the fuel-hormone response to prolonged (3 hr), low intensity cycle ergometer exercise (40% maximal aerobic power) which in the untrained state fails to produce a rise in blood lactate, was examined in six healthy male subjects. The training program consisted of one hour cycle ergometer exercise performed 4 times weekly for 6 weeks and resulted in a 19% increase in maximal aerobic power. Prior to training, prolonged low intensity exercise resulted in a 20% decline in plasma glucose, a 2.5-fold rise in plasma free fatty acids (FFA), a 7-fold rise in plasma epinephrine, a 3-fold elevation in plasma norepinephrine, and a 2.5-fold rise in plasma glucagon. Following training, the exercised-induced decline in glucose was 60% less than before training, the elevations in plasma FFA and norepinephrine were respectively, 45% and 90% less than before training and no significant increment in plasma norepinephrine and glucagon was observed. Training also blunted the exercise-induced elevations in circulating ketones and growth hormone and resulted in a lower respiratory exchange ratio during exercise. The data indicate that training markedly diminishes the fuel-hormone perturbations associated with low intensity exercise and in the face of a lessened increment in plasma FFA results in a greater utilization of fat and less dependence on carbohydrate during the exercise.

Adolescent↗