Biomedical subjects

K Ratheiser

Publications and source records attributed to K Ratheiser.

44 records · Page 3Linked to original sources

PubMed1989

Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. Evidence for multiple sites of insulin resistance.

The effect of graded, physiologic hyperinsulinemia (+5, +15, +30, +70, +200 microU/ml) on oxidative and nonoxidative pathways of glucose and FFA metabolism was examined in nine lean non-insulin dependent diabetic patients (NIDDM) and in eight age- and weight-matched control subjects. Glucose and FFA metabolism were assessed using stepwise insulin clamp in combination with indirect calorimetry and infusion of [3H]3-glucose/[14C]palmitate. The basal rate of hepatic glucose production (HGP) was higher in NIDDM than in control subjects, and suppression of HGP by insulin was impaired at all but the highest insulin concentration. Glucose disposal was reduced in the NIDD patients at the three highest plasma insulin concentrations, and this was accounted for by defects in both glucose oxidation and nonoxidative glucose metabolism. In NIDDs, suppression of plasma FFA by insulin was impaired at all five insulin steps. This was associated with impaired suppression by insulin of plasma FFA turnover, FFA oxidation (measured by [14C]palmitate) and nonoxidative FFA disposal (an estimate of reesterification of FFA). FFA oxidation and net lipid oxidation (measured by indirect calorimetry) correlated positively with the rate of HGP in the basal state and during the insulin clamp. In conclusion, our findings demonstrate that insulin resistance is a general characteristic of glucose and FFA metabolism in NIDDM, and involves both oxidative and nonoxidative pathways. The data also demonstrate that FFA/lipid and glucose metabolism are interrelated in NIDDM, and suggest that an increased rate of FFA/lipid oxidation may contribute to the impaired suppression of HGP and diminished stimulation of glucose oxidation by insulin in these patients.

Blood Glucose↗

PubMed1987

Different effects of glyburide and glipizide on insulin secretion and hepatic glucose production in normal and NIDDM subjects.

Glyburide (GB) and glipizide (GZ) differ in their pharmacokinetics, but it is not known whether they also differ in mode of action. To examine this question, 10 young healthy subjects and 6 non-insulin-dependent diabetic (NIDDM) patients participated in each of three studies: 1) infusion of saline for 120 min followed by a 100-min hyperglycemic (125 mg/dl) clamp; 2) 120-min primed continuous infusion of GZ followed by a 100-min hyperglycemic clamp; and 3) 120-min primed continuous infusion of GB followed by a 100-min hyperglycemic clamp. The GB and GZ infusions were continued throughout the hyperglycemic clamp. Similar plasma concentrations of GB and GZ were obtained in both groups. All studies were performed with [3-3H]glucose to allow quantification of hepatic glucose production. When administered under basal conditions of glycemia, the acute phase (0-10 min) of plasma insulin and C-peptide increase in both control and NIDDM subjects was twice as great with GZ compared with GB (P less than .01). During the hyperglycemic-clamp studies performed in normal subjects, both GB and GZ increased the first- (1.6-fold) and second- (2.2-fold) phase plasma insulin responses more than hyperglycemia alone. During the hyperglycemic clamp in NIDDM subjects, the first-phase plasma insulin response was absent, and the second-phase insulin response was markedly impaired. Neither GB nor GZ improved first-phase insulin secretion in the NIDDM patients. In both NIDDM and control subjects, the effects of hyperglycemia and sulfonylurea drugs (both GB and GZ) on the first- and second-phase plasma insulin responses were simply additive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1986

Lymphocyte membrane lipid composition and mitogen responsiveness in chickens: role of membrane "fluidity".

After establishing optimal conditions for measuring the membrane lipid packing density ("fluidity") of chicken peripheral blood lymphocytes, the fluidity was modulated in vitro by incubation in cholesterol or phospholipid ("active lipid", AL)-enriched serum-free tissue culture medium. The effect of these lipids on mitogen responsiveness was then investigated, the aim being to determine whether the observed enhancement/suppression was membrane mediated, i.e. explainable by fluidity changes. Chicken peripheral blood lymphocytes exhibited no requirement for exogenous cholesterol; low concentrations did not affect the mitogen response while the higher concentrations, which induced a measurable decrease in membrane fluidity, were usually mildly suppressive. Pre-incubation did not increase this suppressive effect and we believe it not to be membrane mediated. AL, at low concentrations which induced no changes in membrane fluidity, prolonged the phytohemagglutinin response, enhancement being evident only after the peak; we interpret this as a nutrient effect. At the higher concentrations, which induced large increases in fluidity, a transient enhancement was followed by suppression; suppression was delayed in onset when AL was added 4 h after phytohemagglutinin stimulation. It is therefore an early event which may be mediated through changes in membrane fluidity.

Animals↗

PubMed1984

Ontogeny of surface markers on functionally distinct T cell subsets in the chicken.

Three subsets of chicken peripheral T cells (T1, T2 and T3) have been identified in peripheral blood of adult chickens on the basis of fluorescence intensity after staining with certain xenogeneic anti-thymus cell sera (from turkeys and rabbits). They differentiate between 3-10 weeks of age in parallel with development of responsiveness to the mitogens concanavalin A (Con A), phytohemagglutinin (PHA) and pokeweed mitogen (PWM). Functional tests on the T subsets, sorted with a fluorescence-activated cell sorter, have shown that T2, 3 cells respond to Con A, PHA and PWM and are capable of eliciting a graft-vs.-host reaction (GvHR). In contrast, although T1 cells respond to Con A, they respond poorly to PHA and not at all to PWM or in GvHR. There was some indication of cooperation between T1 and T2,3 cells for the PHA response. Parallels between these chicken subsets and helper and suppressor/cytotoxic subsets in mammalian systems are discussed.

Aging↗

PubMed1984

Lack of correlation between serum cholesterol levels, lymphocyte plasma membrane fluidity and mitogen responsiveness in young and aged chickens.

Chickens were studied in an attempt to demonstrate correlations between serum lipid levels and peripheral blood lymphocyte (PBL) plasma membrane fluidity and mitogen responsiveness: (a) in the laying hen; (b) during aging; and (c) following dietary manipulation of serum cholesterol of young and aged chickens. The membrane fluidity of PBL from laying hens was significantly greater than that of immature birds. However, no direct correlation was found between serum lipid levels, nor the serum free cholesterol/phospholipid (FC/Pl) mole composition and PBL membrane fluidity in any of the age-groups tested. Likewise, no correlation was found either between serum FC/Pl mole ratio or membrane fluidity and mitogen responsiveness of PBL from birds up to 5 years of age nor was there any evidence for a decline in mitogen responsiveness up to this age. Supplementation of diets with 1% cholesterol induced hypercholesterolemia, mainly in the very low density lipoprotein (VLDL) fraction, but membrane fluidity and mitogen responsiveness remained unaffected.

Aging↗

PubMedDate not supplied

Quantitative and qualitative differences in basal and glucose- and arginine-stimulated insulin secretion in healthy subjects and different stages of NIDDM.

To determine quantitative and qualitative differences in insulin secretion equimolar amounts of glucose and arginine were infused in 9 healthy subjects, in 8 individuals each with obesity without and with impaired glucose tolerance, and in non-obese and obese non-insulin-dependent diabetic patients (NIDDM). Insulin secretion was calculated after individual determination of metabolic clearance rate of C-peptide (MCRcp) both as the area under the C-peptide concentration curve times MCRcp, and by a mono-compartment mathematical model, both yielding identical results. MCRcp fell consistently with increasing C-peptide infusion rate (e.g.: healthy subjects: C-peptide, 10 nmol/h, 4.2 +/- 0.4; 20 nmol/h, 3.3 +/- 0.3; 30 nmol/h, 3.1 +/- 0.2 ml/kg.min; p less than 0.05 to p less than 0.01). Basal insulin secretion was 2.1-fold greater in the obese with impaired glucose tolerance than in healthy subjects, but was unchanged in non-obese NIDDM. Glucose and arginine triggered insulin release was greater than in healthy subjects at almost identical area under the respective substrate concentration curve (AUC/kg body weight) in obese subjects without (2-fold) and with impaired glucose tolerance (4-fold), and in NIDDMs following i.v. arginine (2-fold). The mean ratio of incremental insulin release to i.v. glucose and arginine was smaller in NIDDM (normal weight, 1.3 +/- 0.4; obese, 1.0 +/- 0.2) than in healthy (2.0 +/- 0.3), or obese subjects with impaired glucose tolerance (2.8 +/- 0.7). Stimulated C-peptide/insulin ratio was reduced in all patients vs that in healthy subjects (p less than 0.05). We conclude that (a) MCR of C-peptide is in part a saturable process; (b) insulin clearance may be impaired in obesity and NIDDM; and (c) insulin secretion differs in obese states and NIDDM both quantitatively and qualitatively, and thereby separates the two disorders as different entities. In addition, quantitation of insulin release in obese states may also help (d) to better define primary algorithms for insulin replacement in normal- and overweight insulin-dependent diabetic patients.

Adult↗

PubMedDate not supplied

Weil disease: importance of imaging findings for early diagnosis.

Weil disease is a rare and severe outcome of infection with leptospires. We report the radiographic appearance of this disease in a patient with hepatic, renal, and pulmonary involvement. Imaging findings added significantly to an early correct diagnosis and, thus, to immediate and successful therapy in this critically ill patient.

Adult↗

PubMedDate not supplied

Use of intravenous lipids in critically ill patients with sepsis without and with hepatic failure.

BACKGROUND: Fat is the preferred energy fuel both in patients with sepsis and with hepatic failure. Thus lipid emulsions should serve as an ideal nutritional substrate in parenteral nutrition. However, previous studies have generated conflicting results on the utilization of artificial lipids in these disease states, and systematic studies in critically ill patients with combined organ dysfunctions and additional complications are lacking. We compared the elimination, hydrolysis, and oxidation of a 20% lipid emulsion in critically ill patients on respiratory support with sepsis and with sepsis plus hepatic failure and in healthy control subjects. SETTING: Medical critical care unit of a university hospital. SUBJECTS AND METHODS: Eight critically ill patients with sepsis, 8 patients with sepsis and decompensated chronic hepatic failure, and 10 healthy volunteers were investigated. Elimination and hydrolysis was evaluated during constant i.v. infusion of 4.5 mg.kg body wt-1.min-1 of triglycerides during 120 minutes. Concentrations of plasma triglycerides, free fatty acids, and glycerol were measured, and elimination parameters were analyzed from plasma curves of triglycerides by using a two-compartment model. Resting energy expenditure and substrate oxidation were measured by indirect calorimetry. RESULTS: In patients with sepsis without and with hepatic failure the rise in plasma triglycerides was blunted and the clearance of triglycerides was enhanced by 20% and 40% (p < .05), respectively, compared with healthy controls. Basal free fatty acid concentrations were elevated, and the rise of free fatty acids and glycerol was comparable to healthy subjects. Energy expenditure was increased and lipid oxidation (as fraction of total energy expenditure) was slightly elevated in both patient groups; the rise in lipid oxidation during lipid infusion was comparable to controls. No side effects or impairment of gas exchange was seen. CONCLUSIONS: In a clinically relevant dosage range, the utilization of an i.v. lipid emulsion, the elimination and hydrolysis of triglycerides, and the lipid oxidation is not impaired in ventilated critically ill patients with sepsis or sepsis and chronic hepatic failure. Lipid emulsions thus are efficiently metabolized in critically ill patients with combined organ dysfunctions and associated sepsis.

Adult↗