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Biomedical subjects

J S Soeldner

Publications and source records attributed to J S Soeldner.

At least 91 records · Page 5Linked to original sources
PubMed1979

Further development and automation of a high pressure liquid chromatography method for the determination of glycosylated hemoglobins.

A previously described high pressure liquid chromatography system for the determination of glycosylated hemoglobin concentrations has been automated and simplified. With this methodology it is possible to perform up to 60 analyses per day for hemoglobin A1a+b% and hemoglobin A1c%. Where an estimate of the total fast hemoglobin alone is required, then a considerably greater number of analyses can be performed. The individual values are calculated directly with an electronic integrator. The mean coefficient of variation of the duplicate determinations of 48 samples was 0.63 +/- 0.83% (mean +/- SD). Aliquots of pooled hemolysates have been maintained in liquid nitrogen at -90 degrees C and run at the beginning and end of each daily analytical run over an 18-mo period. Both the inter- and intra-run coefficients of variation of these values have remained consistently less than 3%. Therefore, the methodology offers a reliable and accurate method of containing glycosylated hemoglobin values for clinical use.

Autoanalysis↗
PubMed1979

Diabetes mellitus and genetic prediabetes. Decreased replicative capacity of cultured skin fibroblasts.

The idea that the gene(s) that cause diabetes mellitus can be expressed in extrapancreatic cells has been examined by tissue culture techniques. Skin biopsies were obtained from 25 normal subjects (N), 26 overt diabetics (D), 16 of juvenile onset (JOD) and 9 of maturity onset (MOD), and 21 subjects genetically predisposed to diabetes (P) on the basis of maturity-onset diabetes in both parents. Each biopsy was subdivided, multiple skin fragments were explanted in vitro, and several parameters of cellular outgrowth were monitored in primary and secondary cultures until cell division ceased because of senescence. In general, the rank order of growth vigor was N greater than P greater than D although differences were often marginal and statistically significant between N and JOD and(or) MOD. Outgrowth of epithelial cells was more vigorous in N explants in early stages, but later, JOD and MOD cells grew better than those of N. Outgrowth of fibroblast cells from N explants was more vigorous both at early and later stages and required less time to achieve maximum percent outgrowth. In secondary cultures, N cells grew faster than the other three groups so that fewer days elapsed between subcultures but significant differences were only seen between N and one or two of the other groups over some of the first seven subcultures. The onset of cellular senescence occurred earlier in P and JOD cultures both in mean population doublings and calendar time. N cultures had a higher percent surviving clones after picking than MOD, and a shorter recloning time than clones of JOD. The replicative life-spans of cultures (mean population doublings +/- SE) were N = 52.54 +/- 2.24, P = 47.84 +/- 2.43, JOD = 47.12 +/- 2.99, and MOD = 46.40 +/- 4.04, but differences did not reach significance for N vs the other three groups. The data demonstrate that cellular growth is impaired in both JOD and MOD types of cultures and to a generally lesser extent in P cultures. This is consistent with intrinsic genetic defects but the possibility that persistent deleterious effects of in vivo pathophysiology contribute alone or in combination cannot be ruled out. Therefore, the diabetic defect(s) can be expressed in extrapancreatic cells of mesenchymal origin. This system should prove useful in exploring the interplay between genetic and environmental factors in diabetes, the mechanisms(s) of hyperglycemia and other metabolic derangements, and the propensity that affected individuals have to develop degenerative diseases.

Adolescent↗
PubMed1979

Metabolic effects of glucose, mannose, galactose, and fructose in man.

The effects of various hexoses upon immunoreactive insulin (IRI) secretion, glucose disposal, and gastric inhibitory polypeptide (GIP) release have been compared in 10 normal nonobese men. Rapid iv infusion (0.5 g/kg in 3 min) of D-mannose resulted in significant ITI release, the peak levels approaching those after D-glucose infusion. D-Galactose, however, was ineffective. The 60-min urine excretions of mannose, galactose, and glucose were 35 +/- 7%, 16 +/- 4%, and 5.5 +/- 0.7% (mean +/- SEM) of the administered dose, respectively. All subjects also received 50 g oral glucose, mannose, galactose, and fructose on different days, each followed by an iv glucose infusion 30 min later. The ingestion of glucose or galactose resulted in a similar increment of GIP (P less than 0.01), followed by a similar increment in the IRI response to iv glucose. Furthermore, the glucose disposal rate increased 2.5-fold compared to that after iv glucose alone (P less than 0.001). However, oral msnnose or oral fructose caused no significant GIP release, yet the IRI response to a subsequent iv glucose load was moderately augmented after oral mannose or oral fructose when compared to iv glucose alone. In addition, there was a similar enhancement of glucose disposal of the iv glucose load after both oral mannose and oral fructose (P less than 0.01). From these studies we conclude that 1) galactose does not elicit IRI secretion per se, yet, like glucose, potentiates GIP and IRI secretion; 2) mannose, despite weak transport across gut or kidney, evokes significant betacytotropic effects; and 3) mannose- and fructose-induced enhancement of glucose disposal might be mediated by a factor(s) other than GIP.

Adolescent↗
PubMed1979

Reproducibility of hemoglobin AIc and sensitivity to various degrees of glucose intolerance.

To establish a normal range of hemoglobin (Hb) AIc, and ascertain the sensitivity and reproducibility of this test, three groups were studied: patients with suspected diabetes undergoing a standard oral glucose tolerance test, diabetic outpatients, and subjects with normal carbohydrate tolerance studies on two separate occasions. In Group 1, the mean Hb AIc (+/- SD) in 165 carbohydrate-tolerant subjects was 4.97 +/- 0.50% and the normal range was the mean +/- 2 standard deviations (4.0 to 6.0%). The mean Hb AIc (+/- SD) of the 63 carbohydrate-intolerant subjects was 6.45 +/- 1.14, significantly greater than the normal subjects. In both subgroups, Hb AIc correlated significantly with the fasting blood glucose but not with the glucose areas of the oral glucose-tolerance test. In Group 2, the Hb AIc values were normal in 39% of those diet treated, 10% of those on oral agents, and none of those on insulin therapy. In Group 3, the mean coefficient of variation of the two Hb AIc values for each subject was 6.86% but was 7.15% for the fasting blood glucose. These findings suggest that Hb AIc is highly reproducible and responsive to minor degrees of abnormality of glucose tolerance and may provide an alternative method for defining carbohydrate tolerance or the degree of blood sugar control.

Adolescent↗
PubMed1979

Biosynthesis of glycosylated hemoglobins in the monkey.

We have investigated the in vivo biosynthesis of the minor hemoglobin components in the rhesus monkey. The elution profile of rhesus hemolysate on BioRex 70 cation exchange resin was analogous to that of human hemolysate. The rhesus Hb Alc peak was identified with the TBA test, which revealed a carbohydrate content identical to that of human Hb A1c. A rhesus monkey was injected with autologous 55Fe-bound transferrin, and the specific activity of each of the minor and major components was followed for over 70 days. As previously shown in man, rhesus Hb alc accumulated specific activity almost linearly over the erythrocyte life-span, indicative of slow and continuous conversion of Hb A0 to Hb Alc. This study revealed two new findings. (1) The specific activity of rhesus Hb Alb was always significantly less than that of Hb Alc. This result suggested that HB Alb is made by further posttranslational modification of Hb Alc. (2) The first portion of rhesus Hb A0 to be eluted on BioRex 70 contained a significant amount of carbohydrate and lower initial specific radioactivity than did the latter portion. This unexpected heterogeneity in the major hemoglobin component reflects slow, nonenzymatic glycosylation at sites other than at the N-terminus of the beta-chain.

Animals↗
PubMed1979

The development of an implantable electrochemical glucose sensor: response to glucose in bovine serum ultrafiltrate.

A glucose sensor based on organic oxidation reactions at a platinum electrode is being developed as the key component for an implantable artificial beta cell for diabetic patients. Sensitivity of a membrane-covered platinum electrode to changing glucose concentration in bovine serum ultrafiltrate has been demonstrated, with current response as high as 60 microamperes per 100 mg/dl change in glucose concentration. Reproducibility of measurements probably will depend on satisfactory mechanical assembly of the membrane-electrode combination. An approach to selectivity based on multiple current measurements is suggested.

Animals↗
PubMed1978

Chronologic and physiologic age affect replicative life-span of fibroblasts from diabetic, prediabetic, and normal donors.

Cultured skin fibroblasts from subjects with clinically apparent diabetes mellitus and from subjects genetically predisposed to diabetes have a replicative lifespan that is inversely related to donor age. Fibroblasts from carefully defined normal subjects not predisposed to diabetes fail to show this correlation. The data support the idea that physiologic status of the tissue donor is a more precise determinant of fibroblast replicative lifespan than chronologic age.

Adolescent↗
PubMed1978

A rapid method for the determination of glycosylated hemoglobins using high pressure liquid chromatography.

Hemoglobin (Hb) Alc is a minor component of Hb found in normal individuals but elevated two or threefold in patients with diabetes mellitus. Limited studies have suggested that the level of Hb Alc is proportional to the integrated concentration of glucose over time. Thus it could serve as an index of hyperglycemia. Its measurement may enable a more objective approach to assessing whether or not the control of hyperglycemia can be correlated with the severity of complications of diabetes. Large scale clinicab studies of Hb Alc have not been undertaken for lack of a rapid assay system. This article describes a method of high pressure liquid chromatography (HPLC) which enables the isolation of Hb Alc in 27 min using only 12 microgram of Hb (100 microliter of blood) and a second method for the isolation of total fast Hb components (also elevated in diabetes) in 11 min. Using the first method, a total of 36 assays were performed on the blood of a single normal volunteer over a one month period. the mean level of Hb Alc was 4.95 +/- 0.12% (SD) +/- 0.02% (SEM), while the coefficient of variation (C.V.) was 2.4%. The mean Hb Alc & b level was 1.65 +/- 0.06% +/- 0.01% (C.V. = 3.6%). Values for Hb Alc in 10 normal individuals were 5.06 (mean) +/- 0.32% (SD) +/- 0.01% (SEM). Hb Alc values in 15 patients with diabetes mellitus ranged from 6.8 to 20.0%. The second method was designed to assay Hb Ala, Hb Alb, and Hb Alc as a single peak and yielded results identical to the sum of these components as determined by the first method ( r = 0.98; p less than 0.001).

Chromatography, High Pressure Liquid↗
PubMed1978

Factors governing insulin and glucagon responses during normal meals.

An experimental model is described which can be used to study substrate and hormone responses to normal meals administered in very near normal circumstances. After 500, 300 and 125 calorie meals, the relative proportion of fat or protein content did not influence the plasma glucose except for minor differences between the high protein-high fat meals. The insulin response to such meals was correlated positively with the increment in glucose but reduction of protein content below 8 g caused a signficant reduction in the increment in plasma insulin per unit increase in plasma glucose. Alterations in protein content above 8 g made no difference. Fat content of the meal did not significantly alter the insulin response. No evidence was obtained for a major component of insulin release attributable to either bulk or preabsorption phenomena such as sight or smell. It is concluded that a significant accentuation of the insulin response to meals is dependent on a minimum amount of protein and that this is probably mediated by one of the gastro-intestinal hormones. Glucagon release is dependent on protein and carbohydrate content of the meal and is independent of the fat content. There may also be an early stimulation of glucagon release, regardless of content, which may also be hormonally mediated.

Adult↗
PubMed1978

A model of glucose-insulin homeostasis in man that incorporates the heterogeneous fast pool theory of pancreatic insulin release.

Current physiologic knowledge about glucose-insulin homeostasis in liver, brain, pancreas, kidney, peripheral tissues, and central vascular organs has been synthesized to form a whole-system mathematical model of glucose metabolism in normal, ideal man. In addition to data of other workers, results from more than 100 intravenous glucose tolerance tests, including variable dosage, variable duration of infusion, and double pulse studies, were used to determine model structure and parameters. Model and clinical testing have focused particularly on the fast phase of insulin response to vascular glucose. The model incorporates blood circulation and equilibration of substances between vascular and interstitial spaces, and it assumes constant fractional clearance of insulin by liver and kidney. Studies using a double pulse of glucose suggest that the time derivative of glucose level is not the sole or predominant influence on fast phase insulin release, but that preinfusion glucose level and/or previous glucose exposure of the pancreas are also important. Variable dosage glucose studies suggest that the amount of insulin released during the fast phase rather than the insulin release rate is regulated by the glucose level. A two-pool, heterogeneous threshold mechanism for beta cell response to glucose is presented that is compatible with the clinical results.

Computers↗
PubMed1978

Reproducibility and comparative analysis of repeated intravenous and oral glucose tolerance tests.

We have developed a methodology for measuring the reproducibility of the oral glucose tolerance test (OGTT) and the intravenous glucose tolerance test (IVGTT) in normal subjects and in offspring of conjugal diabetic parents. Both groups of subjects revealed more striking correlations of several parameters of blood glucose and insulin secretion between two IVGTTs than between two OGTTs. Employing arbitrary criteria, we calculated a "reproducibility index" as a quantitative measure of blood glucose variability in each subject. No significant difference was found in the reproducibility of OGTT versus IVGTT, nor in normals versus the offspring. Only about 50 per cent of the tests in normals and in the offspring could be considered to be "reproducible." The offspring revealed greater correlations of several parameters, particularly insulin secretion, between the two IVGTTs and between the two OGTTs as compared with the normal group. However, the blood glucose variations tended to be considerably greater in the offspring from one to the other test.

Administration, Oral↗
PubMed1977

"Somatostatinoma": a somatostatin-containing tumor of the endocrine pancreas.

We studied the pancreatic and enteric hormone profile of a 46-year-old woman who had hyperglycemia and a pancreatic tumor. Before operation, there was no evidence of overproduction of glucagon or insulin. The tumor's ultrastructure had a distinctive endocrine morphology, resembling D cells. Prompted by the recent demonstration of somatostatin in D cells of pancreatic islets, we analyzed the tumor and found a large quantity of immunoreactive somatostatin (301 ng per milligram of tissue). Insulin, glucagon, gastrin, vasoactive intestinal polypeptide and human pancreatic polypeptide were present in only trace quantities. The tumor cells were cultured in monolayers, which remained viable up to 51 days and released somatostatin into the culture medium. In seven insulinomas and two glucagonomas, we found the somatostatin content either much lower (less than 0.6 ng per milligram of tissue) or undetectable. After complete resection of the tumor, our patient became euglycemic and has remained so for the past 20 months.

Cells, Cultured↗
PubMed1977

Portacaval diversion for severe hypercholesterolemia. Report of a case with measurements of glucose tolerance, insulin, and glucagon levels.

An end-to-side portacaval shunt was performed in a patient with severe coronary arteriosclerosis and type IIa hypercholesterolemia. By one year postoperatively there was a decrease of serum cholesterol concentration of more than 40%. No adverse side effects were noted. Intravenous and oral glucose tolerance tests were performed and were within normal range preoperatively and postoperatively. However, preoperatively, during the oral test, the serum insulin levels exceeded the normal range. In addition, glucagon levels revealed less tendency to suppression during the preoperative oral tests. Psychological testing revealed no abnormalitites, and serum ammonia levels were only slightly elevated.

Adult↗
PubMed1977

Metabolic and endocrine studies in a case of lipoatrophic diabetes.

A 20-yr-old female with congenital lipoatrophic diabetes was studied, with the following findings: (1) Serum insulin levels increased after both oral glucose and intravenous arginine administration; there was no growth hormone response to the latter. (2) The infusion of insulin (0.1 units and 0.5 units/kg) during the fed state and following at 110-hr fast produced only minimal changes of various fuels measured, with the exception of a decrease in the branched-chain amino acids. (3) There was a minimal production of ketones during the 110-hr fast. (4) Matabolic expenditure was markedly increased during the postabsorptive state (65-75 kcal/hr/sg m); it fell into the normal range during the 110-hr fast (31-35 kcal/hr/sq m). (5) Following meals, the patient experienced complaints ranging from cold and shivering to feeling hot with gross diaphoresis. These findings were associated with intermittent lability of her skin temperature, which varied 1 degree - 2 degrees F during a 3-hr period. (6) Progressive increases in doses of regular insulin before each meal resulted in up to a total of 9000 units/day being required before normal blood glucose levels were achieved. (7) A 2-wk therapeutic trial of pimozide provided no significant changes in a variety of hormones and fuels in the basal state or following insulin perturbations. (8) A variety of pituitary hormones and pituitary target organ hormones were studied in both the hypothyroid (Hashimoto's thyroiditis) and euthyroid state (following thyroid replacement). All the hormone responses were normal except that growth hormone did not rise during the slow wave sleep in either thyroid state.

Adult↗
PubMed1977

Deranged insulin-secretory dynamics in offspring of two diabetic parents after double stimulation with intravenous glucose.

Nine offspring of two diabetic parents and 18 normals were studied with two intravenous glucose loads (o.5 gm./kg. body weight), 60 minutes apart. By thus stressing the beta cell, subtle defects could be identified in the prediabetics: (1) An inverse relationship between insulin peak response and insulin concentration 60 minutes postglucose was seen, a phenomenon exactly the opposite to that seen in normals. (2) Insulin peak response was delayed slightly after the first pulse and significantly after the second. (3) A less effective handling of the glucose load when compared with normals was brought out by the second stimulation. (4) There was a significant reduction in the insulin response per unit change in glucose after the first glucose pulse that was accentuated after the second pulse. This double-stimulation technique amplifies previously detected slight but significant defects in insulin secretion that might help to identify a diabetes-prone population.

Adolescent↗