Publications by authors named "Wahren J"

The effects of hyperinsulinemia, hyperglycemia, and the route of glucose administration on total glucose utilization and on net splanchnic glucose exchange were studied in 20 normal volunteers with the hepatic venous catheter technique. Euglycemic hyperinsulinemia [induced by a priming plus continuous infusion of insulin resulting in plasma insulin levels of 400-1200 muunits (international)/ml and a variable glucose infusion] caused a 5- to 6-fold increase above basal in total glucose turnover. However, net splanchnic glucose uptake (0.

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Glucose (100 g) was ingested 15 min after bicycle exercise until exhaustion at a work load corresponding to 70% of maximal uptake (series 1), 14--15 h after an identical exercise period, no food being taken in the interval (series 2), and by nonexercised control subjects. Splanchnic glucose output in the exercised groups rose to values 50--300% greater than in controls, amounting to (over 135 min) 59 +/- 5 g in series 1 and 58 +/- 6 in series 2 compared to 28 +/- 6 in controls. The glycogen concentration of quadriceps muscle in series 1 was 65 +/- 2 mmol glycosyl U/kg wet wt before exercise, 16 +/- 13 at the end of work, and 32 +/- 4 at 135 min after glucose ingestion.

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1. The concentration of metabolites in intercostal and quadriceps muscle, and pulmonary function, were studied in twelve patients with chronic obstructive lung disease and acute respiratory failure before, during and after standardized treatment at an intensive care unit. The findings were compared with those obtained in hospitalized patients of comparable age with non-pulmonary diseases.

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In normal man, the fasting state is characterized by release of alanine and glutamine from muscle and in situ muscle catabolism of branched chain amino acids (lecucine, isoleucine, and valine). The alanine released by muscle is utilized by the liver for gluconeogenesis. Muscle nitrogen repletion occurs during protein feeding primarily by means of selective hepatic escape and muscle uptake of branched chain amino acids in ingested protein.

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Cyclic somatostatin was administered intravenously (10 mug/min for 60 min) to 10 healthy overnight fasted (postabsorptive) subjects and to 5 healthy 60-h fasted subjects. In both groups, arterial insulin and glucagon fell 50% and splanchnic release of these hormones was inhibited. In the overnight fasted subjects splanchnic glucose output fell 70%, splanchnic uptake of lactate and pyruvate was unchanged, alanine uptake fell by 25%, and glycerol uptake rose more than twofold in parallel with an increase in arterial glycerol.

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The turnover of plasma free oleic and arachidonic acids was determined in five healthy women before and after 3 months contraceptive treatment with a daily dose of 0.05 mg ethinyl estradiol and 0.25 mg d-norgestrel administered in a cyclic manner.

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Somatostatin was infused for 5-8 hr into five normal men and eleven normal, conscious dogs. This infusion resulted in a persistent decline in plasma glucagon (40-60%) and insulin (30-45%). Plasma gluccose fell 15-25% during the initial 1-2 hr, but subsequently rose to hyperglycemic levels (130-155 mg/100ml) by 3-6 hr, despite persistent hypoglucagonemia.

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Infusion of somatostatin, an inhibitor of glucagon secretion, in insulin-dependent diabetics resulted in a 75-100% reduction in the blood-glucose rise after oral glucose administration, but did not improve intravenous glucose tolerance. Somatostatin reduced blood-xylose levels by 50-90% after ingestion of this pentose and delayed the peak increment in blood-xylose by 1-2 h. Similar effects on blood-xylose levels and a 30% reduction in splanchnic blood-flow were observed in normal subjects during infusion of somatostatin.

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Studies are reviewed in which the roles of insulin and glucagon in normal physiology and in diabetes are examined. In normal man, glucose ingestion is accompanied by a rise in insulin and fall in glucagon and is primarily disposed of in the liver, an organ sensitive to both hormones. However, infusions of glucagon in physiologic amounts indicate that insulin secretion rather than glucagon inhibition is the primary factor determining glucose disposal.

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Hypoglucagonemia (induced by somatostatin) and hyperglucagonemia (induced by infusion of physiologic amounts of glucagon) have only evanescent effects on blood glucose regulation. Despite on-going glucagon suppression by somatostatin, fasting hyperglycemia develops within 4-6 hr of insulin suppression, indicating that (1) basal glucagon secretion is not essential for the development of the diabetic state; and (2) insulin-deficiency (rather than altered glucagon secretion) is the dominant long-term factor determining glucose homeostasis in the diabetic. With respect to hyperglucagonemia, only a transient increase in splanchnic glucose output is observed in normal and diabetic subjects in response to physiologic increments in this hormone.

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To evaluate the effects of physiologic hyperglucagonemia on splanchnic glucose output, glucagon was infused in a dose of 3 ng/kg per min to healthy subjects in the basal state and after splanchnic glucose output had been inhibited by an infusion of glucose (2 mg/kg per min). In the basal state, infusion of glucagon causing a 309 +/- 25 pg/ml rise in plasma concentration was accompanied by a rapid increase in splanchnic glucose output to values two to three times basal by 7-15 min. The rise in arterial blood glucose (0.

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The inter-organ flux of substrates after a protein-rich meal was studied in seven healthy subjects and in eight patients, with diabetes mellitus. Arterial concentrations as well as leg and splanchnic exchange of amino acids, carbohydrate substrates, free fatty acids (FFA), and ketone bodies were examined in the basal state and for 3 h after the ingestion of lean beef (3 g/kg body wt). Insulin was withheld for 24 h before the study in the diabetic patients.

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Sodium L(+)-lactate was infused at rates of 5 to 12 mmol/min intravenously for 30 min in health volunteers, and the exchange of lactate, glucose, and free fatty acids (FFA) was measured in the leg, the forearm muscle, and the splanchnic region. Arterial lactate levels were 3 to 5 mmol/l during the infusion. Leg blood flow increased about 2.

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Turnover rates and metabolism in the legs and the splanchnic region of free stearic and oleic acid have been studied in five healthy male volunteers at rest and during bicycle exercise. A continuous infusion of 14C-labeled stearic acid and tritiated oleic acid was given intravenously. At rest, the fractional turnover was the same for the two acids; the fractional leg uptakes were also similar, while fractional uptake in the splanchnic region was 80% higher for oleic than for stearic acid.

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Substrate utilization by the nonexercising leg was studied in healthy subjects during one-leg exercise at an average work load of 105 W for 40 min (n equals 8) or during arm exercise at 65 W for 20 min (n equals 5). During one-leg exercise both the blood flow and the A-FV difference of oxygen for the non exercising leg rose, resulting in an approximately five fold increment in oxygen uptake. EMG activity of the leg was increased above basal.

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1. Leg blood flow, uptake of oxygen and glucose and release of lactate by the leg and changes in intramuscular concentrations of metabolites were studied at rest and during exercise of increasing work loads in thirteen patients with occlusive disease of the iliac or superficial femoral arteries. 2.

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