Biomedical subjects

A H Rubenstein

Publications and source records attributed to A H Rubenstein.

At least 199 records · Page 11Linked to original sources

PubMed1975

Prolonged suppression of insulin release by insulin-induced hypoglycemia: demonstration by C-peptide assay.

Pancreatic beta cells secrete the proinsulin connecting peptide (C-peptide) and insulin on an equimolar basis. The C-peptide can thus be used as an indicator of endogenous insulin secretion in the presence of exogenously administered insulin. Using this approach, we have shown suppression of endogenous insulin release in healthy subjects during hypoglycemia induced by intravenous infusion of porcine insulin. Moreover, the suppression persists after the plasma glucose returns to fasting levels, suggesting that the recovery of beta cells from the effects of hypoglycemia is not immediate.

Adult↗

PubMed1975

Carbohydrate and lipid metabolism in the Alaskan Arctic Eskimo.

The effect of a low total carbohydrate low sucrose diet on various parameters of lipid and carbohydrate metabolism was studied among residents of a North Slope Alaskan Eskimo village. For comparative purposes a group of Eskimo youths consuming a higher carbohydrate institutional diet was also stidied. Those Eskimos consuming their native diet had unusually low serum triglycerides and very low density lipoproteins and normal glucose and tolbutamide tolerance tests. Eskimos on a higher carbohydrate diet exhibited significant elevations of triglycerides and minor alterations in glucose tolerance testing. Differences in cholesterol intake between these groups were accompanied by changes in serum cholesterol and low density lipoprotein levels. Unusually high levels of free fatty acids without ketonemia in the North Slope sample were noted as well.

Adolescent↗

PubMed1975

Insulin and the kidney.

Changes in renal function and structure are frequently observed in patients with diabetes mellitus. In the early phases of the disease, alterations in glomerular filtration rate, renal plasma flow, glomerular permeability and tubular capacity for glucose reabsorption occur. In the late stages of juvenile onset diabetes, renal failure is a common cause of death. For this reason, increasing attention is being paid to the possibility of long-term dialysis and renal transplantation in these patients. The kidneys play an important role in regulating insulin metabolism. The renal arteriovenous difference is approximately 30-45% and a linear relationship exists between the arterial insulin level and the renal arteriovenous concentration difference. The renal extraction of insulin is 200 ml/min in man, and it is estimated that 6-8 U are removed and degraded by the kidney in 24 h. The quantity of insulin in urine is small. However, its clearance is relatively constant over a wide range of serum concentrations and is 0.15-0.5 ml/min. The mean basal insulin excretion is 3.6 muU/mg creatinine, and a fourfold rise occurs following a glucose load. The urinary insulin values in neonates, children and patients with diabetes and renal failure are reviewed. In diabetic patients, progressive renal disease is accompanied by decreasing insulin requirements. In contrast, nondiabetic patients who develop renal failure frequently show abnormalities in carbohydrate metabolism, the commonest of which is a pseudodiabetic state.

Carbohydrate Metabolism↗

PubMed1975

Proinsulin, insulin, and C-peptide concentrations in human portal and peripheral blood.

Concentrations of insulin, proinsulin, and C-peptide were measured in portal and peripheral venous blood in six nondiabetic, nonobese subjects. Portal vein samples were obtained by umbilical vein catheterization. Three subjects were studied with intravenous infusion of 25 g glucose, and three with 30 g arginine. Insulin and proinsulin were determined in the insulin immunoassay after separation by gel filtration, and C-peptide was measured by direct immunoassay. With both glucose and arginine stimulation, portal vein levels of all three peptides peaked at 90-120 s after the onset of the stimulus. Relative increases in insulin concentration were greater than those of proinsulin or C-peptide. In peripheral venous blood, maximal levels of the three peptides were observed later (2-5 min), and the increase in insulin relative toproinsulin and C-peptide was not as great. At the time of peak secretion, portal vein insulin and C-peptide approached equimolar concentrations, and proinsulin, as measured against an insulin standard, comprised approximately 2.5% of the total immunoreactive insulin. After stimulation by glucose or arginine, portal insulin, proinsulin and C-peptide levels were not correlated with the concentrations measured in simultaneously drawn peripheral samples. At all sampling times, however, significant correlation was found between insulin and C-peptide in both peripheral and portal blood. The results indicate that under the conditions studied, insulin and C-peptide are secreted in equimolar concentrations in man, and that proinsulin is secreted in the same proportion to insulin as found in the pancreas. Consideration of the relative secretory and metabolic rates of the three beta cell peptides explains their peripheral concentrations. The data further support the use of plasma C-peptide as an indicator of beta cell secretory function.

Antigens↗

PubMed1975

Peripheral metabolism of insulin, proinsulin, and C-peptide in the pregnant rat.

To clarify alterations in carbohydrate metabolism which occur in pregnancy, metabolic clearance rates of insulin, proinsulin, and C-peptide were measured by the constant infusion technique in term-pregnant rats and in virgin littermates. In addition, placental permeability to these peptides was evaluated by simultaneous determination of their concentration in fetal blood, amniotic fluid, and maternal arterial blood and the renal extraction and excretion of insulin and C-peptide were determined during simultaneous studies of renal hemodynamics. The metabolic clearance rate (MCR) of insulin was higher (P less than 0.005) in pregnant animals (61.5+/-1.7 ml/min per kg nonconceptus body weight) than in virgin littermates (51.5+/-2.2 ml/min per kg). Insulin disappearance from the circulation after both single injection and discontinuance of a constant infusion was also faster in gravid animals. In contrast, the MCR of proinsulin and C-peptide, and the disappearance of C-peptide from the circulation were similar in pregnant and control rats. The placenta was virtually impermeable to each of the three polypeptides since their mean levels in both fetal blood and amniotic fluid did not exceed 2.5 ng/ml and were only minimally influenced by pharmacological concentrations as high as 60 ng/ml in the maternal circulation. The renal clearance of insulin (renal arteriovenous insulin difference X renal plasma flow) was lower, and its contribution to insulin MCR was less in pregnant animals than in controls (19.4+/-1.5% vs. 28.7+/-3.7%, P less than 0.05), whereas the renal clearance and renal clearance/MCR of C-peptide were similar in pregnant rats and virgin littermates. These results indicate that the peripheral metabolism of insulin is accelerated in pregnancy, while that of pro-insulin and C-peptide is unaffected. Since transplacental passage of insulin is negligible and its renal clearance is not increased, the enhanced MCR of insulin in pregnancy is due to increased metabolism at an extrarenal site probably within the placenta itself.

Amniotic Fluid↗

PubMed1975

Carbohydrate metabolism in pregnancy: XIII. Relationships between plasma insulin and proinsulin during late pregnancy in normal and diabetic subjects.

To assess the effects of pregnancy on the relationships between plasma insulin and proinsulin, studies were performed during late gestation in women with normal carbohydrate metabolism or diabetes mellitus. Plasma was secured after overnight fast and 1, 2, and 3 hours following oral glucose (100 g). Samples were analyzed directly for total immunoreactive insulin (TIR) and for insulin and proinsulin following plasma fractionation by gel filtration. Fractionation disclosed that most of the normal gestational increase in basal and glucose-stimulated TIR can be ascribed to insulin rather than disproportionate increments in proinsulin-like components. Normal proinsulin/insulin relationships were also preserved in mild diabetics despite greater variability in their TIR response to glucose. Thus, mild carbohydrate intolerance during pregnancy is not attended by abnormalities in plasma proinsulin. In contrast basal proinsulin levels were elevated in 4 of 9 pregnant subjects with diabetes sufficiently severe to necessitate subsequent insulin therapy. Following glucose administration in the severe diabetics, the relative contribution from proinsulin to TIR was altered so that ratios of circulating proinsulin/insulin were increased at all levels of blood sugar. Postpartum tests of glucose tolerance in some of the normal and mildly diabetic subjects confirmed that pregnancy per se does not modify appreciably the relationships between plasma insulin and proinsulin although there may be some tendency for proinsulin to account for a smaller proportion of TIR.

Blood Glucose↗

PubMed1975

Serum proinsulin in children and adolescents with chemical diabetes.

Proinsulin levels (PLC) in serum were determined after gel filtration on specimens obtained during oral glucose tolerance testing (OGTT) in seven patients with repeated abnormality in OGTT and in a group of seven control subjects matched for age. Fasting and thirty-, sixty-, and 120-minute postglucose venous samples were analyzed for glucose (PG) and immunocreactive insulin (IRI) as well as PLC, PG and IRI mean concentrations were greater at all testing times in the patient population, but the mean IRI/PG was significantly higher in the patients only at fasting. PLC mean levels were higher in the patients but not to a level of significance. Percentage of total IRI atributable to PLC at each time point was identical between the two groups. The apparcent diminished effectiveness of circulating insulin in chemical diabetes cannot be attributed to an abnormal proportion of proinsulin.

Adolescent↗

PubMed1975

Plasma C-peptide and diagnosis of factitious hyperinsulinism. Study of an insulin-dependent diabetic patient with "spontaneous" hypoglycemia.

Factitious hyperinsulinism was suspected in a patient with an 11-year history of insulin-dependent, ketosis-prone diabetes mellitus who began to experience repetitive episodes of "spontaneous" hypoglycemia. Insulin mediation of the hypoglycemia was confirmed by documenting that urinary insulin and total extractable insulin in plasma increased during periods of hypoglycemia. Failure to detect significant amounts of human C-peptide by radioimmunoassay during periods of hypoglycemia or in response to stimulation with glucagon, leucine, or tolbutamide indicated that the insulin was not endogenous. The diagnosis of factitious hyperinsulinism was ultimately proved by the finding of radioactivity in the patient's urine after 131-I Hippuran was added to a vial of insulin found in the patient's room.

Diabetes Mellitus↗

PubMed1975

Insulinoma with low circulating insulin levels: the diagnostic value of proinsulin measurements.

Hypoglycemia coexisting with very low plasma immunoreactive insulin concentrations was found in a 78-year-old woman with an insulinoma. However, the absolute proinsulin levels during hypoglycemia were elevated (0.9 to 1.4 ng/ml), accounting for 66.5% of the total circulating immunoreactive insulinlike material. The raised serum proinsulin concentrations together with an abnormal proinsulin:insulin ratio proved to be of critical importance in establishing the diagnosis of an islet-cell tumor in this patient.

Adenoma, Islet Cell↗

PubMed1975

Degradation of insulin in serum by insulin-specific protease.

The effect of insulin specific protease (ISP) in degrading plasma insulin over a wide concentration range was studied. In sera containing more than 50 muU per milliliter, more than 85 per cent of the insulin was destroyed. However, a smaller percentage of the hormone was degraded in sera containing less than 20 muU per milliliter and the results were highly variable. The residual insulin-like immunoreactivity in plasma after exposure to ISP thus represents both undegraded insulin as well as proinsulin. These findings explain the higher plasma proinsulin values obtained by the enzyme method when compared to gel filtration.

Antigens↗

PubMed1975