Search PubMed⌕ Search

Biomedical subjects

P Felig

Publications and source records attributed to P Felig.

At least 19 recordsLinked to original sources
PubMed1991

Normalization of hepatic glucose regulation despite systemic insulin delivery. Studies in patients with pancreatic transplantation for type 1 (insulin-dependent) diabetes mellitus.

With current surgical techniques for pancreatic transplantation, the graft is anastomosed to the iliac vessels, resulting in delivery of insulin to the systemic circulation rather than to the portal vein as in healthy man. The possible influence of the altered route of insulin delivery on the regulation of splanchnic glucose metabolism was studied in four patients with Type 1 (insulin-dependent) diabetes mellitus at 6-19 months after combined pancreatic and kidney transplantation. Four non-diabetic, age-matched renal transplant recipients and two groups of age-matched healthy subjects served as controls. The studies were carried out in the basal state and during two rates of intravenous glucose infusion (2 and 4 mg.kg-1.min-1). Fasting arterial glucose and splanchnic glucose output was similar in all groups. Basal hyperinsulinaemia was present in pancreatic graft recipients compared to healthy subjects. During low rate intravenous glucose infusion splanchnic glucose output decreased to a similar extent in all groups. With the higher glucose infusion rate (4 mg.kg-1.min-1) a net glucose uptake was observed which was similar in all three groups. Peripheral glucose uptake was unchanged at the lower glucose infusion rate but increased by 45-55% at the higher rate. It is concluded that despite systemic insulin delivery from a heterotopic pancreatic graft, hepatic glucose metabolism appears normal both in the post-absorptive state and in response to glucose-stimulated endogenous insulin secretion. Portal insulin delivery is thus not necessary for normal hepatic glucose metabolism in the Type 1 diabetic patient.

Adult↗
PubMed1989

Splanchnic and renal exchange of infused fructose in insulin-deficient type 1 diabetic patients and healthy controls.

Fructose raises blood glucose and lactate levels in normal as well as diabetic man, but the tissue origin (liver and/or kidney) of these responses and the role of insulin in determining the end products of fructose metabolism have not been fully established. Splanchnic and renal substrate exchange was therefore examined during intravenous infusion of fructose or saline in six insulin-deficient type I diabetics who fasted overnight and in five healthy controls. Fructose infusion resulted in similar arterial concentrations and regional uptake of fructose in the two groups. Splanchnic glucose output increased threefold in the diabetics but remained unchanged in controls in response to fructose infusion, and the arterial glucose concentration rose more in diabetics (+5.5 mmol/liter) than in controls (+0.5 mmol/liter). Splanchnic uptake of both lactate and pyruvate increased twofold in response to fructose infusion in the diabetics. In contrast, a consistent splanchnic release of both lactate and pyruvate was seen during fructose infusion in controls. In diabetics fructose-induced hyperglycemia was associated with no net renal glucose exchange, while there was a significant renal glucose production during fructose infusion in the controls. In both groups fructose infusion resulted in renal output of lactate and pyruvate. In the diabetics this release corresponded to the augmented uptake by splanchnic tissues. In two diabetic patients given insulin infusion, all responses to fructose infusion were normalized. Fructose infusion in diabetics did not influence either splanchnic ketone body production or its relationship to splanchnic FFA inflow. We conclude that in insulin-deficient, mildly ketotic type I diabetes, (a) both the liver, by virtue of lactate, pyruvate, and fructose-derived gluconeogenesis, and the kidneys , by virtue of fructose-derived lactate and pyruvate production, contribute to fructose-induced hyperglycemia; (b) outcome of hepatic fructose metabolism; and (c) fructose does not exert an antiketogenic effect. These data suggest that while total fructose metabolism is not altered in diabetics, intermediary hepatic fructose metabolism is dependent on the presence of insulin.

Adult↗
PubMed1988

Psychologic issues in diabetes care.

A clear perception of the psychologic factors affecting both the physician and the patient can greatly influence the course of therapy in diabetes. Genuine, realistic assessment and acceptance of the limitations inherent in physician-patient interactions will lead to considerably more satisfying personal and professional relationships.

Adaptation, Psychological↗
PubMed1986

Amino acid and glucose metabolism in the postabsorptive state and following amino acid ingestion in the dog.

Amino acid and glucose metabolism was studied in nine awake 18-hour fasted dogs with chronic portal, arterial, and hepatic venous catheters before and for three hours after oral ingestion of amino acids. The meal was composed of a crystalline mixture of free amino acid, containing neither carbohydrate nor lipid. Following the amino acid meal, plasma glucose concentration declined slowly and this occurred despite a rise in hepatic glucose release. Portal plasma insulin rose transiently (30 +/- 7 to 50 +/- 11 microU/mL, P less than 0.05) while the increase in portal glucagon was more striking and persisted throughout the study (162 +/- 40 to 412 +/- 166 pg/mL). Over the three hours following amino acid ingestion, the entire ingested load of glycine, serine, phenylalanine, proline, and threonine was recovered in portal blood as was 80% of the ingested branched chain amino acids (BCAA). The subsequent uptake of these glucogenic amino acids by the liver was equivalent to the amount ingested, while hepatic removal of BCAA could account for disposal of 44% of the BCAA absorbed; the remainder was released by the splanchnic bed. During this time, ongoing gut production of alanine was observed and the liver removed 1,740 +/- 170 mumol/kg of alanine, which was twofold greater than combined gut output of absorbed and synthesized alanine. In the postcibal state, the total net flux of alanine and five other glucogenic amino acids from peripheral to splanchnic tissues (1,480 mumol/kg 3 h) exceeded the net movement of branched chain amino acids from splanchnic to peripheral tissues (590 mumol/kg/3 h).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1986

Splanchnic and peripheral glucose and lactate metabolism during and after prolonged arm exercise.

Splanchnic and peripheral exchange of glucose and gluconeogenic substrates was examined in 12 healthy subjects during 2 h of arm or leg exercise on a bicycle ergometer and during a 40-min postexercise recovery period. The work intensity corresponded to 30% of the maximal pulmonary oxygen uptake. The regional exchange of substrates was evaluated using catheter technique and indicator dilution methods for blood flow measurements. Our findings indicate that prolonged arm exercise as compared with exercise with the legs results in a greater increase in heart rate (25-40%) and a more marked reduction in splanchnic blood flow (10-30%) as well as higher arterial concentrations of lactate, free fatty acids, and catecholamines. The respiratory exchange ratio was consistently higher with arm exercise. In addition, arm exercise results in a greater fractional extraction and utilization of glucose by exercising muscle as well as a greater hepatic gluconeogenesis from lactate and glycerol. During recovery from prolonged arm exercise, leg muscle becomes an important site of lactate release to the splanchnic bed, despite a lack of net glucose uptake by the leg. Simultaneously, arm muscle shows an increase in glucose uptake in the absence of a net release of lactate. These coincident but discordant processes in the leg and arm during recovery suggest the occurrence of a redistribution of muscle glycogen from previously resting (leg) muscle to previously exercising (arm) muscle.

Adult↗
PubMed1986

Hepatic glucose production and splanchnic glucose exchange in hyperthyroidism.

Hepatic glucose production (HGP) and net splanchnic glucose balance (NSGB) were simultaneously determined in the basal state in 8 hyperthyroid patients and 10 normal subjects using iv infusion of [3H]3-glucose and the hepatic venous catheter technique. Splanchnic glucose uptake (SGU) was calculated as the difference between the HGP and NSGB. SGU was also measured by determining the splanchnic extraction ratio of [3H]3-glucose across the splanchnic bed. In 5 hyperthyroid patients and 5 normal subjects a renal vein was also catheterized in the basal state. The influence of increased endogenous insulin secretion [stimulated by a low rate iv infusion of glucose (2 mg/kg . min)] on splanchnic and hepatic glucose exchange was also examined. Basal HGP (measured with [3H]3-glucose) was increased by 20% in the hyperthyroid patients [14.2 +/- 0.6 (SEM) mumol/kg . min] as compared to normal subjects (11.9 +/- 0.6, P less than 0.02). In marked contrast, NSGB output was slightly but not significantly decreased in the hyperthyroid group. SGU in the hyperthyroid patients, as determined with both techniques, was more than 2-fold higher than in the normal group (P less than 0.02-P less than 0.005). Splanchnic uptake of gluconeogenic precursors (lactate, pyruvate, glycerol) was increased by 20-120% in the patient group. During iv infusion of glucose, plasma insulin levels increased more in the hyperthyroid group (66% vs. 37%, P less than 0.05). Nevertheless, HGP and NSGB were less markedly suppressed in the patients as compared to the normal subjects (P less than 0.01), whereas the augmented SGU in the hyperthyroid patients reverted to normal. Splanchnic uptake of gluconeogenic precursors was unchanged in both groups. No net renal glucose production could be demonstrated in either group in the basal state. We conclude that in hyperthyroidism, increased HGP occurs in the face of an unchanged or slightly reduced rate of net glucose delivery to extrasplanchnic tissue. This discrepancy can be ascribed to augmented splanchnic uptake of glucose. These findings raise the possibility of futile cycling of glucose in the liver as a mechanism of increased oxygen consumption in hyperthyroidism. The data also demonstrate a diminished inhibitory effect of endogenous insulin on splanchnic glucose production, suggesting the presence of hepatic resistance to insulin in hyperthyroidism.

Adult↗
PubMed1986

Continuous subcutaneous insulin infusion (CSII) reduces counter-regulatory hormone concentrations in a patient receiving enteral hyperalimentation.

A 61-year-old male, while recovering from a Whipple's procedure for pancreatic carcinoma, was treated for 13 days with an insulin infusion pump for diabetes exacerbated by enteral hyperalimentation. Treatment with continuous subcutaneous insulin infusion resulted in improved blood glucose control. Associated with this improvement was a reduction in plasma cholesterol, triglyceride and free fatty acid levels. Plasma epinephrine, norepinephrine, glucagon and cortisol concentrations were also lowered although growth hormone levels remained unchanged. It is concluded that enhanced metabolic control during hyperalimentation results in a decrease in counter-regulatory hormone levels and an improvement in the catabolic state in this patient. These preliminary observations provide evidence for maintaining euglycemia in diabetic patients while receiving nutritional support.

Blood Glucose↗
PubMed1984

The plasma amino acid response to cafeteria feeding in the rat: influence of hyperphagia, sucrose intake, and exercise.

The plasma amino acid response to voluntary hyperphagia was evaluated in rats fed a "cafeteria" diet for 4 to 8 weeks and compared to chow-fed controls. The influence of the sucrose content of the cafeteria diet was examined by studying rats given a low-sucrose, highly palatable, liquid diet (Magnacal). In a second series of studies the cafeteria diet was fed to rats housed in wheel cages and who ran 2.0 +/- 0.1 milles per day and compared with a sedentary cafeteria-fed group housed in standard cages. As expected, the cafeteria diet resulted in hyperphagia (45% to 55%) and in increased weight gain (35% to 50%). In response to cafeteria feeding there was an increase in plasma threonine, serine, proline, citrulline, alpha-amino butyric acid (ABA), and tyrosine. Significant decreases were observed in the branched chain amino acids (BCAA), valine and leucine. All of these changes were also observed when hyperphagia was induced with the low-sucrose diet, with the exception of the rise in ABA. In the exercised cafeteria-fed rats, excessive weight gain did not occur. Nevertheless, the amino acid response to the cafeteria diet was the same as in sedentary rats with excessive weight gain. The plasma amino acid pattern in those rats that developed glucose intolerance during cafeteria feeding and those that maintained normal glucose tolerance was similar. We conclude that hyperphagia induced by cafeteria feeding in the rat results in a specific plasma amino acid profile characterized by elevations in some amino acids (threonine, serine, proline, citrulline, ABA, and tyrosine) and reductions in the BCAA.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1984

Role of basal glucagon levels in the regulation of splanchnic glucose output and ketogenesis in insulin-deficient humans.

The aim of the present study was to investigate the influence of hepatic glycogen depletion and increased lipolysis on the response of splanchnic glucose output and ketogenesis to combined glucagon and insulin deficiency in normal man. Healthy subjects were studied after a 60-h fast and compared with a control group studied after an overnight fast. Net splanchnic exchange of glucose, gluconeogenic precursors, free fatty acids (FFA) and ketone acids were measured in the basal state and during intravenous infusion of somatostatin (9 micrograms/min) for 90-140 min (overnight fasted subjects) or for 5 h (60-h fasted subjects). During the infusion of somatostatin, euglycemia was maintained by a variable intravenous infusion of glucose. Prior to somatostatin infusion, after an overnight (12-14 h) fast, splanchnic uptake of glucose precursors (alanine, lactate, pyruvate, glycerol) could account for 26% of splanchnic glucose output (SGO) indicating primarily glycogenolysis. Somatostatin infusion resulted in a 50% reduction in both insulin and glucagon concentrations and a transient decline in SGO which returned to baseline values by 86 +/- 11 min at which point the glucose infusion was no longer necessary to maintain euglycemia. Arterial concentrations of FFA and beta-OH-butyrate and splanchnic beta-OH-butyrate production rose 2.5-fold, 6-fold and 7.5-fold, respectively, in response to somatostatin infusion. In the 60-h fasted state, basal SGO (0.29 +/- 0.03 mmol/min) was 60% lower than after an overnight fast and basal splanchnic uptake of glucose precursors could account for 85% of SGO, indicating primarily gluconeogenesis. Somatostatin administration suppressed the arterial glucagon and insulin concentrations to values comparable to those observed during the infusion in the overnight fasted state. SGO fell promptly in response to the somatostatin infusion and in contrast to the overnight fasted state, remained inhibited by 50-100% for 5 h. Infusion of glucose was consequently necessary to maintain euglycemia throughout the 5-h infusion of somatostatin. Splanchnic uptake of gluconeogenic precursors was unchanged during somatostatin despite the sustained suppression of SGO. Basal arterial concentration and splanchnic exchange of beta-OH-butyrate were respectively 22-fold and 6- to 7-fold elevated and basal FFA concentration was 70% increased as compared to the corresponding values in the overnight fasted state.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1984

Insulin is the mediator of feeding-related thermogenesis: insulin resistance and/or deficiency results in a thermogenic defect which contributes to the pathogenesis of obesity.

Obesity is characterized by insulin resistance which predisposes to the development of impaired glucose tolerance. It is postulated that in addition to its role in carbohydrate metabolism, insulin is the mediator of feeding-related increases in thermogenesis (the thermic effect of food and dietary-induced thermogenesis). The development of insulin resistance and/or deficiency is postulated to result in a decrease in feeding-related, insulin-mediated thermogenesis. As a consequence of this thermogenic defect there is an increase in efficiency of weight gain which accelerates the development and facilitates the maintenance of the obese state. Abnormalities in the insulin axis are thus not only involved in the pathogenesis of the carbohydrate intolerance of obesity but are also proposed as having a central role in a dysregulation of energy balance which contributes to the pathogenesis of obesity.

Body Temperature Regulation↗
PubMed1984

Influence of exercise on urea, creatinine, and 3-methylhistidine excretion in normal human subjects.

To evaluate the effects of exercise on net protein catabolism, the losses of urea in sweat and urine and urinary creatinine and 3-methylhistidine (3MH) excretion were determined in eight healthy subjects during cycle ergometer exercise performed at approximately 45% of VO2max for 90 min. The subjects ingested a meat-free diet for 5 days starting 3 days before and continuing for 1 day after the day of exercise. During exercise, total urea excretion (urine + sweat losses) increased 100% above pre- and postexercise values. Thirty percent of the total urea excretion during exercise was in the form of sweat losses. Total protein breakdown (as reflected by urea excretion), however, could account for less than 5% (21 +/- 4 kcal) of total calorie expenditure during the exercise (567 +/- 83 kcal). Urinary creatinine excretion increased by 50% during exercise. Urinary excretion of 3MH also tended to rise, but the ratio of urinary 3MH to creatinine showed no change in response to exercise. We conclude that 1) light to moderate exercise results in an increase in net protein catabolism and an increase in creatinine excretion; 2) sweat losses are an important route for urea excretion during exercise; 3) there is no evidence of a disproportionate increase in breakdown of myofibrillar contractile proteins; and 4) in spite of the increase in the rate of protein catabolism, protein is only a minor source of energy during light to moderate exercise.

Adolescent↗