Biomedical subjects

A J Szabo

Publications and source records attributed to A J Szabo.

At least 19 recordsLinked to original sources

PubMed1985

Hypertension, orthostatic hypotension and the microvascular complications of diabetes.

Prevalences of hypertension and orthostatic hypotension and their relationship to the microvascular complications of diabetes were assessed in 702 individuals aged 18-74 years, who had been selected as a representative sample of surviving patients with diabetes diagnosed at the Joslin Clinic between 1939 and 1965. In diabetes of short, long and very long duration, hypertension was 1.7, 1.9 and 2.1 times more frequent, respectively, than in the white U.S. population, regardless of gender. The excess frequency of hypertension in short duration diabetes suggests that some etiologic factor is shared by both conditions, while the magnification of the excess with increasing duration could be explained by an effect of diabetes on the kidney. Hypertension without accompanying proteinuria was not associated with retinopathy. Orthostatic hypotension was observed in 12% of the males and 13% of the females. The magnitude of the fall in systolic blood pressure was correlated with age, postprandial blood glucose, supine diastolic blood pressure, and the presence of retinopathy. Patients with proliferative retinopathy had the largest fall in systolic blood pressure.

Adult↗

PubMed1983

Insulin injected into CNS structures or into the carotid artery: effect on carbohydrate homeostasis of the intact animal.

A synopsis is presented of studies (anatomical, immunohistological, immunochemical, and physiological) that suggested the presence of insulin receptors, native insulin, insulin-responsive cells, and insulin-sensitive glucoregulatory regions (centers) in the CNS. Evidence and consideration at variance with the above were also briefly listed. The controversies related to this new field of investigations are far from settled; they will provide a fertile field for exciting pioneering work for many investigators in the near future.

Animals↗

PubMed1983

Vagotomy or atropine blocks hypoglycemic effect of insulin injected into ventromedial hypothalamic nucleus.

Stereotaxic microinjections of insulin (100 microU) into the ventromedial hypothalamic nucleus (VMN) resulted in rapid decrease, whereas injection of control saline into the same region caused a slight increase of hepatic venous plasma glucose concentration in rats. The hypoglycemic effect of insulin injected into the VMN was eliminated by pretreatment of the animals with atropine but not with propranolol or with phentolamine. Subdiaphragmatic vagotomy also prevented the decrease of hepatic venous plasma glucose concentration seen after microinjection of insulin into the VMN. These results support the hypothesis that the VMN is an insulin-sensitive glucoregulator center or that it is part of one and that the glucoregulatory impulse that originates in the VMN reaches the effector organ, the liver, through the cholinergic fibers of the vagus nerves.

Animals↗

PubMed1981

Decrease in plasma glucose concentration after microinjection of insulin into VMN.

The influence of insulin on hypothalamic regulation of blood sugar homeostatis was studied in anesthetized rats. Insulin was injected directly into the ventromedial hypothalamic nucleus (VMN), the lateral hypothalamic area (LHA), the parietal cortex, or the third cerebral ventricle, and changes in hepatic venous plasma glucose concentrations were studied. After injection of 100 microU insulin into the parietal cortex or the third ventricle, hepatic venous plasma glucose concentration did not differ from that of the control rats, which received saline injection into the same CNS regions. Saline injection into the LHA raised the hepatic venous plasma glucose concentration in control rats, where injection of 100 microU insulin into the LHA resulted in a modest but significant decrease of glycemia in the 2-, 5-, and 10-min postinjection samples. As little as 10 microU insulin injected into the VMN eliminated the hyperglycemic response seen in control rats after saline injection into this site. The divergence between insulin-treated rats and their saline-treated controls was further amplified, and an actual fall of plasma glucose was observed in rats given injections of 50 or 100 microU insulin into the VMN. Increasing quantities of insulin (from 10 to 100 microU) injected into the VMN resulted in graded decreases of hepatic venous plasma glucose concentrations, suggestive of a dose-response curve. These observations support the hypothesis that the VMN and the LHA are parts of an insulin-sensitive CNS glucoregulator system that exerts influences on the systemic blood glucose levels by causing rapid alterations in hepatic glucose metabolism.

Animals↗

PubMed1979

Transjugular hepatic vein cannulation in rats with nonisotopic in vivo verification.

A simple, rapid and relatively atraumatic method for transjugular cannulation of the hepatic vein and for repeated sampling of hepatic venous blood in the rat is described. Preliminary in vivo verification of the cannula's position is proposed, either by using the glucose differential between consecutive samples of the hepatic venous blood and inferior vena cava blood, or more practically, by using the glucose differential between the hepatic venous blood and tail blood obtained simultaneously. The latter procedure is favored because of its technical simplicity.

Animals↗

PubMed1975

Influence of the insulin sensitive central nervous system glucoregulator receptor on hepatic glucose metabolism.

Excitation of the insulin sensitive glucoregulator receptor in the central nervous system (C.N.S.) causes an immediate decrease in the systemic blood sugar level in rats. 2. A study was made in animals that were subjected either to evisceration or to evisceration and functional-hepatectomy, in order to assess the role of the liver and pancreatic hormones in the blood sugar decrease following insulin injection into the carotid artery. 3. The results indicate that the change in the systemic blood sugar level, induced by exposing the C.N.S. to insulin, was effected through a direct influence of the receptor centre on glucose metabolism of the liver. 4. Excitation of the insulin-sensitive receptor in the C.N.S. regulates carbohydrate metabolism of the liver, both by inhibiting hepatic glucose output and by facilitating hepatic glucose uptake. 5. The data derived from these animal models reveal that the mode of transmission of the impulse from the C.N.S. region is through efferent neural pathways that directly influence the hepatic carbocydrate metabolism, and not through a modification of pancreatic hormone secretion.

Animals↗

PubMed1975

Neuropharmacological characterization of insulin-sensitive CNS glucoregulator.

Regional insulinization of the central nervous system (CNS) through the carotid artery causes an immediate decrease of the systemic blood sugar level in rats under light barbiturate anesthesia. Cervical vagotomy or intraperitoneal or intravenous atropine pretreatment results in partial inhibition of the systemic hypoglycemic response that follows intracarotid insulin injection. Intraperitoneal, intravenous, or intracarotid pretreatment with phentolamine or propranolol or intracarotid pretreatment with epinephrine had no effect on this centrally induced hypoglycemia. Intracarotid atropine injection immediately prior to intracarotid insulin injection completely abolished the systemic hypoglycemic response. Pretreatment with neostigmine administered intravenously prevented the inhibitory effect of intracarotid atropine on the hypoglycemic response that followed intracarotid insulin injection. It is consluded that the insulin-sensitive glucoregulator center of the CNS is under cholinergic influence, or its efferent pathways have a centrally located cholinergic synapsis.

Animals↗

PubMed1975

The effect of hypophysectomy on the function of the insulin-sensitive central nervous system glucoregulator receptor.

Hypophysectomized and healthy control rats were studied to investigate the mechanism of action of the insulin-sensitive glucoregulator receptor of the central nervous system (CNS). Glucagon-free insulin (500 muU) was injected into the carotid artery, and the peripheral blood glucose was monitored. An immediate significant fall in the blood sugar was observed in intact as well as in hypophysectomized rats. To control these experiments buffer was injected into the carotid artery, or 500 muU insulin was given through the jugular vein of intact and hypophysectomized animals. The systemic blood sugar level remained unchanged for 10-15 min in the control experiments. The results indicate that the function of this insulin-sensitive glucoregulator CNS receptor is not impaired in the hypophysectomized state. The initial phase of its effect, the sudden decrease of the blood sugar level, appears to be independent of pituitary hormone secretion.

Animals↗

PubMed1975

Studies on the nature and mode of action of the insulin-sensitive glucoregulator receptor in the central nervous system.

In vivo studies were undertaken in rats to provide evidence of the neural nature, tentative localization and mode of excitation of the insulin-sensitive central nervous system (CSN) glucoregulator center. In rats under light barbiturate anesthesia minute amounts of insulin injected into the carotid artery resulted in an immediate decrease of the systemic blood sugar. This hypoglycemic action of regional insulinzation of the CSN was lost when the animals were subjected to prolonged, deep barbiturate narcosis. Competitive inhibition of glucose utilization in the CSN region by intracarotid administration of 2-deoxy-D-glucose did not block the systemic hypoglycemic effect of subsequent intracarotid insulin injection. Chronic endogenous hyperinsulinemia produced by daily growth hormone treatment resulted in an insensitivity of the CNS glucoregulator center to exogenous insulin. The ratio of the quantity of the injected insulin and the pre-existent plasma insulin concentration showed direct correlation with the systemic hypoglycemic response that followed intracarotid injection. Present data support the hypothesis that the insulin-sensitive glucoregulator center located in the area supplied by the carotid artery is neural in nature, because of its inhibition by barbiturate anesthesia. The data are compatable with the working hypothesis that the center is located in the hypothalamus, since light cortical barbiturate anesthesia did not, but deep anesthesia did have an inhibitory effect on it. Marked interference by chronic hyperinsulinemia suggests that the receptor center estimates the metabolic status of the animal through means related to physicochemical binding of insulin to specific receptors. However, since our attempt to inhibit glucose utilization in the CNS was without effect on the activity of the center, it appears that the singal for the glucoregulatory impulse is not insulin facilitation of glucose utilization in the receptor area, but another parameter of insulin action.

Alloxan↗

PubMed1974