Control of blood sugar in insulin-dependent diabetes: comparison of an artificial endocrine pancreas, continuous subcutaneous insulin infusion, and intensified conventional insulin therapy.

We compared the ability of closed-loop intravenous insulin infusion (i.e., an artificial "pancreas"), open-loop continuous subcutaneous insulin infusion, and intensified conventional insulin therapy (preprandial injections of regular insulin, with injection of long-acting zinc-suspension insulin before breakfast) to bring the hyperglycemia of insulin-dependent diabetic subjects to a level comparable to that of normal, nondiabetic subjects.

Branched-chain amino acid nitrogen transfer to alamine in vivo in dogs. Direct isotopic determination with [15N]leucine.

To investigate the contribution of branched-chain amino acids as a nitrogen source for alanine in vivo, dogs were infused with l-[(15)N]leucine, l-[U-(14)C]leucine, l-[2,3,3,3-(2)H(4)]alanine, and d-[6,6-(2)H(2)]-glucose. (14)C and (15)N isotopic equilibrium in plasma leucine, and deuterium enrichment in arterial and femoral plasma glucose and alanine were achieved within 3 h of initiation of the respective isotope infusion in all animals. The average flux of leucine determined by [(15)N]leucine was 5.

Adrenergic mechanisms of catecholamine action on glucose homeostasis in man.

To assess the adrenergic mechanisms responsible for the effect of epinephrine on glucose production and glucose clearance in man, epinephrine (50 ng/kg/min) was infused in the presence and absence of alpha adrenergic (phentolamine) and beta adrenergic (propranolol) antagonists under conditions when plasma glucose, insulin, and glucagon levels were allowed to vary and when they were clamped by a concurrent infusion of glucose, somatostatin, and insulin. When plasma glucose, insulin, and glucagon were permitted to vary during beta adrenergic blockade, plasma glucose and glucose production increased, respectively, 32% and 42% less and plasma epinephrine concentrations were threefold greater than those during infusion of epinephrine alone; plasma insulin decreased during beta blockade but increased during infusion of epinephrine alone; glucose clearance was comparably suppressed in both instances. When alpha adrenergic blockade was superimposed on beta blockade, the increase in glucose production and the decrease in both plasma insulin and glucose clearance observed during infusion of epinephrine alone was virtually abolished.

Epinephrine and norepinephrine are cleared through beta-adrenergic, but not alpha-adrenergic, mechanisms in man.

Although catecholamines are rapidly removed from the extracellular fluid, the role of adrenergic mechanisms in the clearance of epinephrine and norepinephrine has not been defined. In five normal human subjects, mean (+/- SE) plasma epinephrine concentrations did not change during control infusions, rose from 21 +/- 6 pg/ml to 834 +/- 84 pg/ml during the infusion of epinephrine (50 ng/kg/min) over 180 min and to 853 +/- 112 pg/ml during the infusion of epinephrine plus phentolamine (500 micrograms/min after a 5.0 mg loading dose infused over 2 min), but to 2400 +/- 104 pg/ml during the infusion of epinephrine plus propranolol (80 micrograms/min after a 5.

Determination of leucine flux in vivo by gas chromatography-mass spectrometry utilizing stable isotopes for trace and internal standard.

A simple and reliable method is described for the determination of leucine flux in vivo using two stable isotopes of leucine and gas chromatography-mass spectrometry (GC-MS). [6,6,6-2H3]Leucine is administered as a primed-dose constant infusion in vivo and DL-[2H7]-leucine is added to plasma as an internal standard. Plasma leucine concentration and moles per cent enrichment of [2H3]leucine can be determined simultaneously by GC-MS and selected ion monitoring.

Alloisoleucine formation in maple syrup urine disease: isotopic evidence for the mechanism.

Of the four possible stereoisomers of isoleucine, only L-alloisoleucine and L-isoleucine were found by capillary gas chromatography in the plasma of two maple syrup urine disease (MSUD) patients, one with classical and one with variant MSUD. The relative plasma concentration ratios of L-alloisoleucine/L-isoleucine were 0.795 +/- 0.

Determination of 14C radioactivity in ketone bodies: a new, simplified method and its validation.

A rapid and reproducible method for the assay of 14C radioactivity in ketone bodies is described, based on the heat lability of acetoacetate and the ability of beta-hydroxybutyrate to quantitatively bind to and elute from an ion exchange resin. Potential interference from 14C activity in the ketone body metabolites (CO2, bicarbonate and acetone) during infusion of 14C-labeled ketone bodies is eliminated. The method was validated both by in vitro recovery studies and by the determination of rates of appearance of ketone bodies during infusion of exogenous unlabeled beta-hydroxybutyrate in dogs.

Effect of alpha-adrenergic stimulation and its blockade on glucose turnover in man.

Epinephrine (50 ng . kg-1 . min-1) was infused for 120 min in seven normal volunteers alone (combined alpha- and beta-adrenergic stimulation), with propranolol (alpha-adrenergic stimulation), and with propranolol plus phentolamine (alpha-adrenergic blockade superimposed on alpha-adrenergic stimulation).

Considerations for the programming of an open-loop insulin infusion device from the biostator glucose controller.

To assess the feasibility of preprogramming an open-loop device with insulin flow rates generated by the Biostator Glucose Controller, comparisons were made in 10 juvenile-onset diabetic patients between meals of equal size and composition taken in the morning, at noon, and in the evening and a bedtime snack during a 24-h period of Biostator glucose control. Four additional diabetic patients had Biostator glucose control for 72 h. Similar amounts of insulin were infused for the meals taken at differing times of the day and, except for the morning meal, for the same meal on two successive days.

Adrenergic mechanisms for the effects of epinephrine on glucose production and clearance in man.

THE PRESENT STUDIES WERE UNDERTAKEN TO ASSESS THE ADRENERGIC MECHANISMS BY WHICH EPINEPHRINE STIMULATES GLUCOSE PRODUCTION AND SUPPRESSES GLUCOSE CLEARANCE IN MAN: epinephrine (50 ng/kg per min) was infused for 180 min alone and during either alpha (phentolamine) or beta (propranolol)-adrenergic blockade in normal subjects under conditions in which plasma insulin, glucagon, and glucose were maintained at comparable levels by infusion of somatostatin (100 mug/h), insulin (0.2 mU/kg per min), and variable amounts of glucose. In additional experiments, to control for the effects of the hyperglycemia caused by epinephrine, variable amounts of glucose without epinephrine were infused along with somatostatin and insulin to produce hyperglycemia comparable with that observed during infusion of epinephrine.

Origin of chi46,XX/46,XY chimerism in a human true hermaphrodite.

Using chromosome heteromorphisms and blood cell types as genetic markers, we demonstrated chimerism in a chi46,XX/46,XY true hermaphrodite. The pattern of inheritance of the chromosome heteromorphisms indicates that this individual was probably conceived by the fertilization, by two different spermatozoa, of an ovum and the second meiotic division polar body derived from the ovum and subsequent fusion of the two zygotes. This conclusion is based on the identification of the same maternal chromosomes 13, 16, and 21 in both the 46,XX and 46,XY cells of the patient.

Overnight basal insulin requirements in fasting insulin-dependent diabetics.

Overnight basal insulin requirements to maintain eugycemia were determined in six insulin-requiring diabetic subjects using a feedback-controlled (closed loop) insulin infusion system. Mean hourly insulin infusion rates, required to maintain plasma glucose concentrations at approximately 100 mg/dl, were remarkably stable from 2400 h to 0600 h; however, a twofold to threefold increase in insulin requirements was observed in each subject between 0600 h and 0900 h. This increase in amount of basal insulin required was not associated with increases in plasma glucagon or growth hormone concentrations, but occurred simultaneously with normal diurnal increases in plasma cortisol.

Defective activation of the pyruvate dehydrogenase complex in subacute necrotizing encephalomyelopathy (Leigh disease).

Autopsy examination confirmed the diagnosis of subacute necrotizing encephalomyelopathy (SNE) in a 7-month-old male infant who underwent several metabolic studies before death. Intermittent lactic acidemia and fumaric aciduria, an extreme hyperglycemic response to an intravenous bolus of alanine, and an elevated total body flux rate of glucose (58.4 mumoles .

Elevated free testosterone in an obese, hirsute premenarchial girl: effects of norethynodrel and mestranol.

An 11-year-old premenarchial girl who demonstrated the clinical and biochemical abnormalities of the Stein-Leventhal syndrome is reported. Although the concentration of total circulating testosterone was within normal limits, levels of free testosterone and testosterone-estradiol-binding globulin (12.9 to 22.

Differential effects of epinephrine on glucose production and disposal in man.

Normal subjects were infused 1) with epinephrine (50 ng/(kg.min)) for 180 min followed by epinephrine plus glucagon (3 ng/(kg.min)) for 60 min after which the epinephrine infusion rate was increased (125 ng/(kg.

Muscle wasting and carbohydrate homeostasis in Duchenne muscular dystrophy.

Carbohydrate homeostasis was evaluated in nine patients with Duchenne muscular dystrophy (DMD), and in six age-matched normal boys. Mild carbohydrate intolerance was observed in the DMD patients during an oral glucose tolerance test. Only minor differences were observed between the DMD patients and the normal subjects during an oral glucose tolerance test.

Renal-resistant hormonoplethoric hypoparathyroidism with evidence for a defective response to cAMP.

A 15.5-yr-old black male is reported with hypocalcemia, hyperphosphatemia, and severe osteitis fibrosa cystica. While hypocalcemic and hyperphosphatemic, the circulating parathyroid hormone (PTH) level and urinary cAMP excretion were increased.

Glucose and alanine metabolism in children with maple syrup urine disease.

In vitro studies have suggested that catabolism of branched chain amino acids is linked with alanine and glutamine formed in, and released from, muscle. To explore this possibility in vivo, static and kinetic studies were performed in three patients with classical, and one patient with partial, branched chain alpha-ketoacid decarboxylase deficiency (maple syrup urine disease, MSUD) and compared to similar studies in eight age-matched controls. The subjects underwent a 24-30-h fast, and a glucose-alanine flux study using stable isotopes.

Metabolic response to hypertonic glucose administration in Reye syndrome.

Blood substrate and hormone concentration were determined in 16 children with Reye syndrome prior to and following administration of hypertonic glucose. Baseline concentrations of lactate, pyruvate, alanine, glutamine, glutamate, proline, hydroxyproline, lysine, and aspartate were elevated (p less than 0.01), whereas citrulline and arginine were low.