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Biomedical subjects

J S Soeldner

Publications and source records attributed to J S Soeldner.

At least 109 records · Page 6Linked to original sources
PubMed1977

Monozygotic triplets with discordance for diabetes mellitus and diabetic microangiopathy.

A set of monozygotic triplets (PE.K., P.K., S.K.) has been studied. There is no diabetes in first-degree relatives. PE.K. developed insulin-requiring (60 U. NPH) diabetes at the age of 13 years. Over a period of 11 years since that time, numerous studies of insulin and growth-hormone secretion were performed on P.K. and S.K., including multiple oral glucose tolerance tests (OGTTs), cortisone-primed oral glucose tolerance tests (C-OGTTs), intravenous glucose tolerance tests (IVGTTs), and intravenous tolbutamide tests (IVTTs). The results of each test were compared with age- and sex-matched control subjects. P. K. developed insulin-requiring (56 U. NPH) diabetes after remaining discordant for eight years. Glucose, insilin, and growth-hormone responses during all tests were normal except during the IVGTT performed four months prior to the onset of diabetes. This last IVGTT revealed a glucose disappearance rate of 0.98 per cent per minute, and the slope of the regression line of serum-insulin response (IRI) on blood glucose (BG) was markedly decreased to 0.005 micronU./ml. IRI/mg./dl. BG (controls 0.340 +/- 0.04; mean +/- S.E.M.). The insulin responses in P.K. and S.K. were similar during all OGTTs, C-OGTTs, and IVTTs. S.K. has continued to maintain normal glucose tolerance and normal insulin and growth-hormone responses during all tests. The histocompability antigen studies have revealed HLA-A2, AW24, BW15, and BW40 phenotype in these monozygotic triplets. Muscle capillary basement membranes of the nondiabetic triplet were normal, whereas both diabetic triplets manifested evidence of capillary basement membrane thickening. The clinical and biochemical profiles in these triplets and the capillary basement membrane data lend strong credence to the role of "nongenetic" determinants in the development of "genetic" diabetes as well as diabetic microangiopathy in juvenile-onset-type diabetes.

Adolescent↗
PubMed1977

Serum insulin response to slow-rise glucose infusion in "genetic prediabetics" (offspring of two diabetic parents).

The insulin response to a programed slow-rise glucose infusion designed to mimic the postprandial rise in glucose was studied in five offspring of two diabetic parents (ODP) and seven normal subjects. The ODP had higher mean blood glucose levels towards the end of the infusion and during the postinfusion period. The rates of glucose disappearance calculate during the postinfusion period were comparable in the two groups. Despite the apparent similarity of serum insulin levels of ODP and normal subjects, the amount of insulin secreted per unit of glycemic stimulus was lower in the ODP group. When the glucose infusion test was preceded by an acute load of glucose, similar findings in the insulin secretory dynamics were found in the ODP group. These data suggest that an impairment in insulin secretion exists in ODP when they are challenged by the slow rise of blood glucose achieved by this type of an intravenous glucose infusion.

Adult↗
PubMed1977

The effects of long-term therapy with oral hypoglycemic agents on the oral glucose tolerance test dynamics in male chemical diabetics.

The effect of fixed doses of oral hypoglycemic agents and placebo (diet alone) on the blood glucose, serum insulin, triglyceride, and cholesterol responses during oral glucose tolerance tests done annually for up to four years' follow-up was studied, in a double-blind manner, in five groups of mild male chemical diabetics. The drugs used were chlorpropamide (100 mg. O.D.), tolbutamide (500 mg. b.i.d.), phenformin (50 mg. O.D.), acetohexamide (250 mg. O.D.), and placebo. Each subject was given an individualized diet aimed at attaining and maintaining ideal weight. Comparison by chi-square analysis between the placebo group and each of the drug groups showed (a) no significant differences with regard to the number of subjects with normal glucose tolerance in each of the tests and (b) no change in the insulin secretion dynamics. Comparison between the initial test and each of the subsequent tests within each group showed (a) a greater number of subjects with normal glucose tolerance in the first follow-up test in the chlorpropamide group only, (b) no change in the insulin secretion dynamics except in the chlorpropamide group, where there was an increased insulin/glucose ratio in the first follow-up test, and (c) no change in the fasting serum triglyceride and cholesterol levels.

Acetohexamide↗
PubMed1976

[The effect of caffeine on the serum insulin level during intravenous glucose tolerance test in patients with chemical diabetes].

Nine mild male diabetic patients were studied by intravenous glucose tolerance tests with and without pretreatment with caffeine. The dose of caffeine was 90 mg given as 195 mg of caffeine citrate. The parameters measured were blood glucose and serum insulin. Caffeine given 2 hours previously did not affect the mean glucose disappearance rate of the group, however, those with the highest rates did show a reduced rate after caffeine. Insulin levels showed a decrease particularly during the first five minutes after glucose. This finding was present particularly in those patients who exhibited the larger first peak. It is possible that a relationship exists between the magnitude of the caffeine effect upon early insulin secretion and the glucose disappearance rate.

Adult↗
PubMed1976

Amino acid levels across normal forearm muscle and splanchnic bed after a protein meal.

To characterize further the role of blood cells in amino acid transport, four normal volunteers were asked to ingest 200 g of broiled ground sirloin within a 10-min period. Blood samples from a radial artery, a deep vein draining forearm muscle bed, and a tributary of the hepatic vein were obtained prior to and for 4 hr after the meal and analyzed for various hormones and substrates. At rest, analysis of arterio-deep venous differences across the forearm revealed the blood cell and plasma amino acid compartmentmental contents to be relatively constant except for alanine and glutamine. Whole blood arterio-hepatic venous (A-HV) amino acid differences were not significantly different from zero; however, blood cell A-HV difference analysis revealed a significant release of threonine from the splanchnic bed while plasma A-HV difference analysis revealed modest but significant releases of glutamate and ornithine and uptakes of phenylalanine and histidine. After the ingestion of the meat meal, plasma and blood cell levels of almost all of the measured amino acids increased significantly. Notable exceptions included glycine and alanine, levels of which did not change significantly and glutamine. The arterial blood cell content of the latter amino acid paradoxically decreased while arterial plasma levels increased significantly. Most importantly, large quantities of branched chain amino acids were released from the splanchnic bed and removed by forearm muscle. These data suggest that the blood cells of normal man do actively participate in amino acid transport, and that the magnitude and direction of change induced by the ingestion of a proteins meal varies with the individual amino acid.

Abdomen↗
PubMed1976

Insulin release is glucose anomeric specific in the human.

The alpha-glucose anomer produces a greater insulin release than beta-glucose in various animal models. These glucose anomers were dissolved rapidly and administered intravenously to human volunteers at a high dose (0.5 g/kg) over a 3-min period or a low dose (3.5 g) over a 20-s period. Blood samples were obtained at frequent time intervals for measurement of whole blood glucose (ferricyanide), plasma glucose (beta-glucose oxidase) and serum immunoreactive insulin. The high-dose infusion test showed no differences between the anomers of either blood glucose or serum insulin levels. However, at the lower dose, the alpha-glucose anomer stimulated a significantly greater insulin release than did beta-glucose. It is concluded that the alpha-glucose anomer stimulates a greater insulin release than the beta-glucose anomer in human subjects at low but not at high doses intravenously and that this response is not apparently related to approximations of the degree of mutarotation. These results suggest that a steric specific glucose receptor site exists on the beta-cell as a rapid insulin release trigger, although the alpha-anomer does not exclusively produce this stimulation.

Female↗
PubMed1976

Hormone-fuel concentrations in anephric subjects. Effect of hemodialysis (with special reference to amino acids).

Arterial blood concentrations of insulin, glucagon, and various substrates were determined in six anephric subjects in the postabsorptive state and immediately after hemodialysis. Plasma glucose and serum insulin concentrations were normal, and declined during dialysis. Plasma glucagon was elevated and remained unchanged. There was moderate hypertriglyceridemia before dialysis, but this decreased significantly after administration of heparin just before the start of dialysis, and at the end of dialysis was lowered further into the normal range. Comparison of postabsorptive whole blood concentrations of amino acids with those in normal, healthy adults revealed striking differences. Glutamine, proline, citrulline, glycine and both 1- and 3-methyl-histidines were increased, while serine, glutamate, tyrosine, lysine, and branched-chain amino acids were decreased. The glycine/serine ratio was elevated to 300% and tyrosine/phenylalanine ratio was lowered to 60% of normal. To investigate the potential role of blood cells in amino acid transport, the distribution of individual amino acids in plasma and blood cell compartments was studied. Despite a markedly diminished blood cell mass (mean hematocrit, 20.6 +/- 1.4%), there was no significant decrease in the fraction of most amino acids present in the cell compartment, and this was explained by increases of several amino acids in cellular water. None were decreased. Furthermore, during dialysis, whole blood and plasma amino acids declined by approximately 30% and 40%, respectively, whereas no significant change was observed in the cell compartment. Alanine was the only amino acid whose concentration declined in the cells as well as in plasma. The results indicate (a) significant alterations in the concentrations of hormones and substrates in patients on chronic, intermittent hemodialysis; (b) removal of amino acids during hemodialysis, predominantly from the plasma compartment, with no significant change in cell content; and (c) a redistribution of amino acids in plasma and blood cell compartments with increased gradients of most of the amino acids per unit cell water, by mechanism(s) as yet undetermined.

Adult↗
PubMed1976

The effect of severe trauma on urine loss of insulin.

Six trauma patients and five healthy volunteers were given an intravenous glucose infusion (5 Gm. per hour) for 6 hours. The serum insulin response and urine insulin excretion were measured and compared in the two groups. Glucose intolerance and serum insulin levels which were elevated but inappropriately low for the degree of glycemia characterized the trauma patients. Urine insulin concentrations and total urine insulin were increased significantly in the trauma patients. Renal function was similar in both groups, as determined by serum creatinine, blood urea nitrogen, and creatinine clearance. The increase in urine insulin concentration in the trauma patients reflected the higher serum insulin concentrations, but no correlation existed between serum insulin and urine insulin concentrations. A negative correlation was found between "insulin clearance" and serum insulin in both groups, indicating altered renal handling of insulin following injury which may be a contributory factor to the relative hypoinsulinemia of trauma.

Adolescent↗
PubMed1976

The direct relationship of proinsulin-insulin hypersecretion to basal serum levels of cholesterol and triglyceride in myotonic dystrophy.

Excessive pancreatic insulin secretory responses to a variety of beta-cytotropic agents have been observed in 40 to 60 per cent of subjects with myotonic dystrophy; in addition, 25 to 30 per cent of affected persons manifest mild glucose intolerance, suggesting that circulating insulin may be biologically ineffective. To test this hypothesis, 8 men with myotonic dystrophy were challenged with a 100 gm. oral glucose load; responses were compared to an age, sex, weight-matched control group. Fasting serum immunoreactive insulin (IRI), cholesterol, and triglyceride levels in the myotonic group did not differ significantly from the controls. In contrast, fasting blood glucose and serum free fatty acid (FFA) levels in the myotonic group were significantly elevated above control, although still within the accepted normal range. Following oral glucose challenge, myotonic subjects exhibited mild glucose intolerance and excessive IRI response, but the FFA and serum alpha-amino nitrogen responses were comparable to control responses. Serum proinsulin was separated from insulin by gel filtration and quantitated by immunoassay. Overall, the proinsulin level in myotonic serum was not greater than the accepted normal level. The mean proinsulin level at the peak serum IRI response during the test was 18.6 +/- 4.1 per cent of the total IRI; 3 myotonic subjects responded with greater than 20 per cent proinsulin. The proinsulin secretory response correlated significantly with basal triglyceride (r = 0.972) and cholesterol (r = 0.794) levels but not with fasting glucose or FFA levels. Peak insulin response was also significantly correlated with triglyceride but not with cholesterol levels. Serum insulin-like activity (ILA) from myotonic dystrophic patients was assessed in vitro employing rat adipose tissue and skeletal muscle in the presence and absence of excess guinea pig anti-insulin serum. Comparison of suppressible insulin-like activity to immunoreactive insulin revealed that the mean biological recovery of serum insulin in these assay systems was 85 to 90 per cent, indicating that endogenous insulin was biologically active on both adipose tissue and skeletal muscle in vitro. We conclude that a biologically ineffective form of circulating insulin does not exist in myotonic dystrophy and that the pancreatic insulin response mechanism may be excessively sensitive, resulting in balanced hypersecretion of proinsulin and insulin. The highly significant correlation between proinsulin and serum triglyceride or cholesterol levels suggests that, in addition to insulin, proinsulin may also exert an important influence on lipid metabolism.

Adult↗
PubMed1976

Species differences in insulin secretory responses during hemorrhagic shock.

Insulin secretory rates (ISR) during intravenous glucose tolerance tests (IVGTT's) were measured in six dogs subjected to hemorrhagic shock and were compared to ISR's from five monkeys subjected to shock of comparable severity. ISR's also were measured in normotensive control dogs and monkeys subjected to the same blood sampling protocol. A sixfold increase in ISR occurred in shocked dogs after glucose loading; however, no ISR response occurred in monkeys subjected to hemorrhage. It is concluded that marked species differences exist in the insulin-glucose metabolic responses to shock. In addition, the dog would appear to be an inappropriate experimental animal as applied to trauma-insulin metabolism in man.

Animals↗
PubMed1976

Lipid, glucose, and insulin interrelationships in normal, prediabetic, and chemical diabetic subjects.

Fasting levels of plasma cholersterol and triglyceride, lipoprotein patterns, and fasting and postintravenous glucose levels of blood glucose, serum insulin, serum growth hormone, and plasma free fatty acids in a genetic potential diabetic population were compared to those in a similar normal control population. THe potential diabetic population was further divided into groups of patients with a normal (prediabetic) or abnormal (chemical diabetic) glucose tolerance test. Although no clear-cut lipid differences were noted, certain trends appeared. More type IV hyperlipoproteinemia was seen in male prediabetic (21%) and male chemical diabetic patients (19%) than in normal male subjects (5%); in female subjects only a few type IV patterns were seen. Type II hyperlipoproteinemia was not seen in any normal subject, but was noted in nearly 9% of those with chemical diabetes. Fasting cholesterol levels correlated better with age than did fasting triglyceride levels in most of the patient groups. Fasting triglyceride levels showed a significant positive correlation with the serum insulin area of the oral glucose tolerance test in the normals wna prediabetic persons, and also showed a significant positive correlation with the blood glucose area of the prediabetic and chemical diabetic patients. It is suggested that a normal relationship between triglyceride concentration and insulin response to glucose is lost in chemical diabetes. Sex differences were also noted in the inslin response and the insulin-glucose relationships during the oral glucose tolerance test, with normal menstruation women showing a significantly lower insulin-glucose relationship than the age-related men.

Adolescent↗
PubMed1976

Mean retinal circulation time as determined by fluorescein angiography in normal, prediabetic, and chemical-diabetic subjects.

A preliminary survey has been completed using manual densitometric technics to determine the mean retinal circulation times in groups of normal controls, offspring to two diabetic parents with normal glucose tolerance (prediabetics), and offspring of two diabetic parents with abnormal glucose tolerance (chemical diabetics). Comparisons of the mean retinal circulation time showed differences between the left eye and right eye in prediabetic and chemical diabetic groups and a sex difference in both normals and prediabetics. In addition, both age and per cent ideal body weight were inversely related to the mean retinal circulation time. The levels of fasting serum cholesterol, triglyceride, and growth hormone, in many instances, also appeared to be inversely related to the mean retinal circulation time. Similarly, the degree of glucose tolerance (determined by the area under the glucose curve above baseline) was significantly inversely related to the mean retinal circulation time. The mean retinal circulation time adjusted for per cent ideal weight was analyzed separately for both right eye and left eye, and a significantly shorter mean retinal circulation time was noted, particularly in males, for prediabetics than for normal controls and for chemical diabetics than for both prediabetics and normals. Analysis of the mean retinal circulation time adjusted for age showed similar differences. It is postulated that the genetic prediabetic state with or without glucose intolerance might be associated with significant alterations of mean retinal circulation time independent of age and per cent ideal weight. It is also suggested that a number of potentially meaningful interrelationships between the degree of glucose intolerance and/or hyperlipidemia might exist and should be further quantified.

Adult↗
PubMed1975

Serum insulin and growth hormone response patterns in monozygotic twin siblings of patients with juvenile-onset diabetes.

To detect abnormalities in the secretion of insulin and growth hormone in monozygotic twin siblings of patients with juvenile-onset diabetes, their responses during oral, cortisone-primed oral, and intravenous, glucose tolerance tests and intravenous tolbutamide tests were compared to those of matched controls. The twins had higher mean serum insulin levels during all tests, but differences reached statistical significance (P less than 0.02) only in the cortisone-primed test. Growth hormone levels were higher in the twins (P less than 0.04) in the intravenous tolbutamide tolerance test. The frequency of abnormal oral glucose tolerance tests among controls, diabetic monozygotic twins and the offspring of two diabetic parents was also compared. Twins and controls had nearly the same frequency of normal tests; however, the diabetic offspring had a significantly higher (P less than 0.001) prevalence of abnormal tests. These data suggest that magnitudes of environmental and genetic factors operating in monozygotic "pre-diabetic" children of diabetic parents.

Adolescent↗
PubMed1975

Alanine-induced amino acid interrelationships.

Six normal subjects received 10 g of alanine both orally and as a 60-min intravenous infusion. In both studies blood samples for hormones and substrates were obtained every thirty minutes for 2 1/2 hour. Significant increases in whole blood levels of threonine, serine, glutamine, proline, glycine, and alpha-amino-n-butyric acid were found, which were mainly due to increases of these amino acids in the plasma compartment. In contrast, whole blood levels of leucine, valine, and isoleucine declined, mainly due to increases in the cell compartment. Plasma glucagon levels increased in both studies while insulin levels rose significantly only during the oral study. Plasma free fatty acids and blood glycerol levels declined while lactate and pyruvate increased. Glucose concentration did not change during both tests. These data suggest that the administration of large quantities of alanine is capable of inducing significant alterations in levels of other amino acids and substrates as well as changing hormone levels.

Adult↗
PubMed1975

Dynamics of tolbutamide, glucose, and insulin interrelationships following varying doses of intravenous tolbutamide in normal subjects.

Four healthy adult subjects received intravenous tolbutamide (TOL) at six different doses (twenty-four tests): 0.0625 gm., 0.125 gm., 0.25 gm., 0.5 gm., 1.0 gm. and 1.5 gm. Blood glucose (BG), serum immunoreacctive insulin (IRI) and serum TOL levels were determined before and for 180 minutes after TOL. There was a highly significant correlation of the dose of TOL with the peak IRI (p less than .01), zero to ten minute IRI area (p less than .001), and zero to sixty minute IRI area (p less than .001) and with the decline in BG expressed as zero to sixty minute BG area (p less than .001). Similar significant correlations were observed between levels of TOL and both IRI and BG. At each dose level the IRI response correlated significantly with the BG fall. An additional eighteen subjects received the 1.0 gm. dose. In these, serum TOL levels did not correlate with either BG or IRI. These subjects also received intravenous glucose (0.5 gm. per kilogram body weight). BG levels did not correlate with IRI. However, there were striking correlations between TOL and glucose-stimulated peak IRI (p less than .001), zero to ten minute IRI area (p less than .05). The mean (plus or minus SEM) space of distribution for glucose (G.S.) and tolbutamide (TLS.) was found to be 13.45 plus or minus 0.71 and 6.34 plus or minus 0.31 L., respectively. There was a significant dose-response relationship exists between TOL and IRI. TOL- and glucose-induced IRI secretion dynamics suggest strong similarities between mechanisms of rapid IRI release and/or size of available IRI storage pools.

Adult↗