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Biomedical subjects

A H Rubenstein

Publications and source records attributed to A H Rubenstein.

At least 145 records · Page 8Linked to original sources
PubMed1978

A prospective study of glucose tolerance, insulin, C-peptide, and glucagon responses in patients with pancreatic carcinoma.

Ninety-nine patients suspected of having pancreatic carcinoma were studied prospectively for carbohydrate tolerance. Thirty-two patients were proven subsequently to have pancreatic carcinoma; the remainder served as a control group. There was an increased incidence of carbohydrate intolerance in patients with pancreatic carcinoma compared to the control group. Insulin and C-peptide measurements during glucose tolerance tests suggest abnormal beta cell function and possibly insulin resistance as causes for this abnormality. Although factors related to malignancy in general could partly account for the results, a specific factor occurring in patients with pancreatic carcinoma must also be considered as it could serve as a marker for the early detection of this disease.

Body Weight↗
PubMed1978

Diabetes and hypoglycemia due to insulin antibodies.

A patient with "autoimmune diabetes" with reactive hypoglycemia due to anti-insulin antibodies is described. The pathophysiology of the impaired carbohydrate tolerance and reactive hypoglycemia is illustrated by measurements of C-peptide, and free and antibody-bound insulin. Detailed analysis of her antibodies did not provide any evidence in favor of exogenous insulin immunization. Nevertheless, a possible cause of unsuspected insulin immunization was present in her history which should be considered in other reported cases of "autoimmune diabetes" due to insulin antibodies in which exposure to insulin cannot be documented.

Adult↗
PubMed1978

Proinsulin and C-peptide in diabetes.

The availability of C-peptide measurement continues to provide new and useful information about the state of beta cell secretory function and the natural history of diabetes. Measurement of proinsulin is of value in the diagnosis of insulin-secreting tumors.

C-Peptide↗
PubMed1978

Plasma glucagon, insulin and glucose responses to intravenous arginine infusion in the rat.

Plasma glucagon (IRG), insulin and glucose responses to intravenous arginine infusion in the rat were studied. Three doses of arginine hydrochloride were infused into fasted rats: 0.2 gm/kg b.w., 0.5 gm/kg b.w., and 1 gm/kg b.w. The 0.2 gm/kg dose did not result in significant elevation of plasma IRG or insulin. Both the 0.5 and 1 gm/kg doses produced a significant increase in glucagon and insulin levels within 5 minutes of starting the infusion. The 1 gm/kg dose was most effective in stimulating secretion of both hormones. This dose produced a 250% rise in the plasma IRG compared to 80% peak rise with the 0.5 gm/kg dose (p less than .01) and 1055% rise in insulin levels compared to a peak level of 225% above baseline with the 0.5 gm/kg dose (p less than .001). These results demonstrate the effectiveness of intravenous arginine in the stimulation of glucagon and insulin secretion in the rat.

Animals↗
PubMed1978

Insulin resistance due to a defect distal to the insulin receptor: demonstration in a patient with leprechaunism.

We have studied a 2-year-old girl with acanthosis nigricans, glucose intolerance, marked hyperinsulinemia, and somatic features characteristic of the leprechaunism syndrome. Circulating plasma insulin levels were increased up to 50-fold and the patient showed a blunted hypoglycemic response to an injection of exogenous insulin (0.2 units/kg), indicating the presence of severe insulin resistance. Insulin purified from the patient's plasma was normal on the basis of chromatographic, electrophoretic, and immunologic criteria. Furthermore, the purified insulin competed effectively with (125)I-labeled insulin for binding to insulin receptors on cultured IM-9 lymphocytes and rat fat cells and also exhibited normal biological potency when tested on rat fat cells. Anti-insulin receptor and anti-insulin antibodies were not detected in the patient's plasma, and plasma levels of glucagon, growth hormone, and cortisol were normal. Insulin binding to the patient's circulating monuclear leukocytes was only slightly depressed into the low normal range and could not account for the severe insulin resistance. Studies on the patient's fibroblasts revealed normal levels of insulin receptors but a total absence of insulin's ability to accelerate glucose transport. Because rates of glucose transport and metabolism were normal in the basal state in the absence of insulin, we conclude that this patient's insulin resistance is due to an inherited cellular defect in the coupling mechanism between occupied insulin receptors and the plasma membrane glucose transport system.

Autoantibodies↗
PubMed1978

Kinetics of human connecting peptide in normal and diabetic subjects.

The metabolic clearance rate (MCR) of synthetic human connecting peptide (C-peptide) was measured with a single-dose injection technique in six normal and seven diabetic subjects and with a constant infusion technique in one normal subject. The MCR of C-peptide did not differ in normal subjects (4.4 ml/min per kg; range, 3.7-4.9) and in diabetic subjects (4.7 ml/min per kg; range, 3.7-5.8). Employment of both techniques in one subject gave similar MCR. The average half-life of C-peptide in plasma calculated from the last 1-h period of the single-dose injection studies was longer in the insulin-dependent diabetics (42.5 min; range, 39.4-48.5) than in the normal subjects (33.5 min; range, 24.9-45.3). These results indicate that the beta-cell secretory capacity of normal and insulin-dependent diabetic subjects can be compared by measuring the C-peptide concentration in peripheral venous plasma. The difference in the half-life of C-peptide in plasma between diabetics and normals suggests an altered kinetics of the disappearance of the peptide, while the overall metabolism, as expressed by the MCR, is similar.

Adult↗
PubMed1978

Glucagon metabolism in the rat.

The renal handling of the biologically active glucagon component (the 3,500-mol wt fraction of immunoreactive glucagon [IRG]) and the contribution of the kidney to its overall peripheral metabolism were studied in normal and uremic rats. The metabolic clearance rate of glucagon was 31.8 +/- 1.2 ml/min per kg in normal animals and was diminished by approximately one-third in each of three groups of rats with compromized renal function: 22.3+/-1.6 ml/min per kg in partially (70%) nephrectomized; 22.9+/-3.3 ml/min per kg in bilaterally ureteral ligated; and 23.2+/-1.2 ml/min per kg in bilaterally nephrectomized animals. In normal rats the kidney contributed 30% to the overall metabolic clearance of the hormone and the renal extraction of endogenous and exogenous glucagon was similar, averaging 22.9+/-1.6% and was independent of plasma IRG levels over a wide range of arterial concentrations. The remnant kidney of partially (70%) nephrectomized animals continued to extract substantial amounts (16.6+/-4.2%) of the hormone, but accounted for only 8% of the total peripheral catabolism of IRG. In the two groups of animals with filtering kidneys, renal glucagon uptake was linearly related to its filtered load and could be accounted for by glomerular filtration and tubular reabsorption. However, the kidneys of animals with both ureters ligated (renal extraction of inulin = 3.2+/-1.8%) and hence virtual absence of glomerular filtration, continued to extract 11.5+/-1.9% of the renal arterial glucagon, contributing by 9% to its overall metabolic clearance, indicating that IRG uptake occurs also from the post glomerular capillaries.

Animals↗
PubMed1978

Synchronous, sustained oscillation of C-peptide and insulin in the plasma of fasting monkeys.

The previously reported synchronous oscillations in plasma glucose and insulin levels have been further studied to determine whether the phenomenon can be attributed to cyclic secretion or degradation of the hormone. Plasma C-peptide concentrations were measured and found to cycle with the same period as plasma insulin suggesting that the oscillations of insulin arise from changing secretion rather than degradation. The amplitude of C-peptide oscillation was 50 percent that of insulin. Assuming first order kinetics and the same relative rates of disappearance as in humans, this difference in amplitudes in consistent with equal secretion rates for the two peptides.

Animals↗
PubMed1978

Direct effect of insulin on secretion of insulin, glucagon, gastric inhibitory polypeptide, and gastrin during maintenance of normoglycemia.

The direct effect of insulin on the secretion of insulin (as measured by C-peptide), glucagon, gastric inhibitory polypeptide, and gastrin was studied in normal subjects by infusing insulin while the plasma level of glucose was maintained in the normal fasting range (euglycemic clamp). Insulin-induced hypoglycemia resulted in increases in circulating glucagon and gastric inhibitory polypeptide, a decrease in C-peptide, and no change in gastrin levels. In contrast, during the euglycemic clamp, insulin was found to behave a direct suppressive effect on the secretion of glucagon, C-peptide, and gastrin, but no effect on levels of gastric inhibitory polypeptide.

Blood Glucose↗
PubMed1978

On the preparation and characterization of standard materials for natural human proinsulin and C-peptide.

The preparation and characterization of intact native human proinsulin and C-peptide to serve as reference standards in immunologic and biologic assays is described. The major difficulty encountered in the preparation of human proinsulin from crystalline human insulin is the rather low yield (0.08 per cent), which may be due to postmortem autolysis in the pancreatic specimens. Under such circumstances, minor degrees of contamination of batches by fresh pancreases from other species, such as cows or pigs, may be magnified considerably. Such contamination can be readily detected with various currently available proinsulin- or C-peptide-specific antisera. Autolysis before or during preparation may also affect the yields and quality of human C-peptide preparations. Some of these C-peptide by-products are described, along with methods for their purification and characterization.

Amino Acids↗
PubMed1978

Characterization of seven C-peptide antisera.

The plasma C-peptide immunoreactivity (CPR) in 10 normal subjects varied considerably when measured with different antisera in parallel assays. The CPR level correlated with the blank "CPR" value measured in plasma devoid of C-peptide and to a lesser degree with the sensitivity of the standard curves obtained with the individual antisera. Storage of plasma samples at different temperatures and for different lengths of time before the analyses were carried out resulted in further variation in the CPR results. This was caused by a time- and temperature-dependent fall in CPR, which was more pronounced with some antisera than with others. This sensitivity to storage of plasma did not correlate with the antigenic characteristics of the antisera as determined by their reactivity with 11 specific fragments of the C-peptide molecule. The contribution of human proinsulin to the CPR concentration relative in normal subjects was considered to be negligible even though the relative immunoreactivity of human proinsulin and C-peptide ranged from 11 to 143 per cent among these antisera. These results suggest that differences in C-peptide antisera are a major reason for the variation in the concentration of circulating CPR as measured in different C-peptide immunoassays.

Animals↗
PubMed1978

Heterogeneity of circulating human C-peptide.

Values reported for serum C-peptide immunoreactivity in healthy individuals vary considerably. To assess factors that contribute to this finding, three human C-peptide assay systems were developed utilizing three distinct antisera that react differently with various C-peptide fragments. Preparations of natural pancreatic and synthetic human C-peptide standards were compared immunologically in these systems. The curves of the natural C-peptide and the synthetic preparations were not identical. The relative immunoreactivity of each standard varied, depending on the particular antiserum used. Serum C-peptide concentrations varied when measured in the different assay systems. Furthermore, the results of dilution and recovery tests and stability of the C-peptide during storage showed differences among the three assays. Gel filtration of serum indicated heterogeneity within the major C-peptide peak, and in addition, a smaller peak of lower molecular weight material was present in some samples. Although degradation of serum C-peptide may occur during storage, fragments of C-peptide may also be secreted or arise during in-vivo metabolism. Thus, the present studies indicate the need for careful standardization and checking of each particular assay system before its use in clinical studies.

C-Peptide↗
PubMed1978

C-peptide in conditions other than diabetes mellitus.

Measurement of serum and urinary C-peptide has been shown to be of value in several conditions other than diabetes mellitus. It is particularly useful because it can distinguish endogenous beta cell secretion from exogenously administered insulin and because circulating insulin-binding antibodies do not interfere with its measurement. Because the liver removes little, if any, C-peptide, peripheral blood values may more accurately reflect beta cell secretion than do peripheral insulin levels. Clinically, serum C-peptide has been most useful in diagnosing hypoglycemic disorders. Diagnosis of insulinomas is facilitated in both diabetic and nondiabetic patients, and surreptitious insulin injection is readily detected. In studies of insulin regulation, circulating C-peptide has been used to demonstrate suppression of endogenous insulin secretion by exogenous insulin. Peripheral insulin and C-peptide levels have been compared in studies of the role of the liver in states of altered insulin homeostasis. Because of its higher urinary clearance, determination of urinary C-peptide is preferable to urinary insulin measurement in situations where frequent blood sampling is impossible or difficult to accomplish.

Blood Glucose↗