Intravenous Injection Of Glucose Research Articles

Plasma catecholamines and carbohydrate metabolism in patients with acute myocardial infarction.

Blood glucose, glucose tolerance, serum insulin, free fatty acids in serum, plasma noradrenaline, and plasma adrenaline were measured in 10 patients with acute myocardial infarction (AMI) as well as in healthy subjects. Both noradrenaline and adrenaline in plasma were elevated in patients with AMI, the level being fairly constant in the individual patients and dependent on their degree of illness. In the fasting state, blood glucose, serum insulin, and free fatty acids were elevated in patients with AMI. Plasma noradrenaline showed a highly significant correlation with the fasting blood glucose concentration, but not with serum insulin or free fatty acids. The concentration of free fatty acids in serum could be predicted only if both plasma noradrenaline and the basal insulin concentration were known. Intravenous glucose tolerance was reduced in patients with AMI, especially in patients with high plasma noradrenaline and a low initial rise in insulin. There was a significant negative correlation between the initial rise in insulin expressed in percentage of the basal insulin concentration and the plasma noradrenaline level. The statistical effects of serum insulin and plasma noradrenaline on the glucose tolerance could not be separated from each other. The decline in free fatty acids after intravenous injection of glucose showed a negative correlation with plasma noradrenaline and a positive correlation with the initial rise in insulin. Plasma adrenaline did not correlate with any of the metabolic parameters mentioned above. The plasma noradrenaline concentration was elevated to such a degree in patients with AMI that the observed changes in metabolism might have been caused directly by the circulating noradrenaline. During the glucose tolerance tests, the effects of noradrenaline was probably carried out indirectly via a suppression of insulin secretion. It is conceivable that any effect of plasma noradrenaline on the basal insulin secretion was neutralized by the fasting hyperglycemia.

Circulating "big" insulin in protein-energy malnutrition.

1. The ‘big’ insulin content of the serums from ten children with protein–energy malnutrition was estimated before, during and after 3–6 weeks of treatment. The values for immunoreactive insulin (IRI) after intravenous injections of glucose were almost normal, with one exception, although tolerance was impaired. In addition, total body potassium content (TBK) was measured for three of the children on each test day.2. In nine of twenty-three estimations ‘big’ insulin content was slightly more than 20% of the total IRI. However, there was a wide fluctuation in the values and no change was noted after treatment.3. The amount of ‘big’ insulin did not correlate with either the magnitude of insulin secretion, the insulin:glucose ratio or TBK. There was a barely significant negative correlation between ‘big’ insulin content and degree of glucose intolerance, with some individual exceptions.

Estimation of the early insulin response to intravenous glucose injection.

Abstract The early insulin response to 25 Gm. glucose intravenously was studied in 29 nonobese, apparently healthy volunteers. The pattern of plasma insulin was followed by frequent sampling during 15 minutes. It showed a wide variation between individuals, but certain features in common could be recognized. The insulin concentration began to rise 1.5 to 3 minutes after the beginning of the injection and reached a maximum at 3 to 8 minutes, most often at 4 minutes. Then, the concentration declined at varying rates. Kinetic analysis of the response curves showed that the release of insulin from the pancreas started almost immediately after the beginning of the injection but lasted for only about 5 minutes. The early response thus reflects a distinct phase, well separated from the later release of insulin. A method is devised for the quantitative estimation of the early response, taking into account also the fraction of the newly released insulin that has disappeared from plasma at the end of the test. The mean value in the group studied was 51 ± 31 μU per milliliter (mean ± S.D.). As a result of these studies, a simple test for determination of the early response is proposed, based on sampling during the first 10 minutes after a single injection of glucose.

Diurnal variation in glucose tolerance and in insulin secretion in man.

The changes in blood glucose and plasma free fatty acid (FFA), insulin, and human growth hormone (HGH) concentrations in response to oral and intravenous glucose and intravenous insulin were measured at 7 a.m. and 7 p.m., on both occasions after a ten hour fast, in thirteen normal males and two juvenile diabetics. Basal concentration of plasma FFA was lower and that of plasma insulin higher in the morning than in the evening. Blood glucose and plasma HGH levels did not differ at these times. In the normal subjects, glucose tolerance was diminished and plasma insulin response was delayed in the evening. The delay was significantly less with intravenous glucose than with oral glucose. When compared with the usually accepted criteria for diagnosis of diabetes mellitus, the normal subjects responded in the evening as mild diabetics. Two juvenile-onset diabetics, who had virtually no increase in plasma insulin concentrations after ingestion or injection of glucose, showed no diurnal variation in glucose tolerance. No diurnal variation was seen in the blood glucose response to intravenously injected insulin or in the plasma clearance rate of insulin; these findings suggest that impairment in glucose tolerance in the evening is due to diminished early insulin response to glucose, rather than to abnormal handling of glucose or insulin. The effect of tolbutamide, phentolamine, and theophylline on the diurnal variation of glucose tolerance was studied. In four subjects, intravenous injection of tolbutamide induced a greater insulin response and a greater fall in the blood glucose concentration in the morning than in the evening. The disappearance rate of intravenously injected glucose and both early and delayed insulin responses to the glucose were enhanced to a much greater degree in the morning than in the evening by the simultaneous intravenous injection of tolbutamide. Intravenous infusion of phentolamine, an alpha-adrenergic blocking agent, in five subjects failed to influence responses to intravenous injection of glucose. Intravenous infusion of theophylline, which inhibits cyclic 3′5′-adenosine monophosphate phosphodiesterase activity, in five subjects potentiated the plasma insulin response to intravenous glucose in the evening but not in the morning; the substance did not influence the disappearance rate of glucose.

Influence of extracorporeal dialysis on glucose utilization and insulin secretion in patients with acute renal failure.

Abstract. The influence of haemodialysis on glucose assimilation, insulin secretion and plasma NEFA was followed in 14 patients with acute renal failure. The results obtained were compared with those from healthy subjects. As has been found in chronic renal insufficiency glucose intolerance was found in patients suffering from acute renal failure. This metabolic aberration was found despite higher mean plasma insulin levels. Treatment by haemodialysis was followed by improvement of glucose assimilation in 10 out of 14 patients. No correlation was found between the improvement of glucose assimilation after haemodialysis and insulin secretion stimulated by intravenous glucose injection. From the results it is concluded that the pathomechanism of glucose intolerance found in patients with acute renal failure does not appear to be uniform and is not necessarily related to insulin secretion.

The glucose receptor. A defective mechanism in diabetes mellitus distinct from the beta adrenergic receptor.

Acute serum insulin responses in 10 normal subjects after rapid intravenous injection of glucose (5 g) or isoproterenol (2 mug) were of similar magnitude and timing (glucose: 431+/-349%; mean Delta3-5' insulin (IRI)+/-SD, per cent basal and isoproterenol: 359+/-216%; mean Delta2-4' IRI+/-SD, per cent basal). To elucidate the relationship of glucose-induced insulin secretion to pancreatic beta adrenergic receptors and the implications of this relationship with regards to abnormal insulin secretion in diabetes mellitus, two questions were studied. (a) To determine whether glucose-induced insulin secretion is dependent upon beta adrenergic activity, the effect of beta adrenergic blockade with intravenous propranolol (0.08 mg/min) upon acute insulin responses to isoproterenol and glucose were compared in normal subjects. (b) To determine whether acute insulin responses to beta adrenergic stimulation were intact in diabetes mellitus, the effect of isoproterenol upon serum insulin levels was studied in diabetic subjects. Beta adrenergic blockade in the normal subjects obliterated acute insulin responses to isoproterenol (before: 361+/-270%, during: - 31+/-15%; n = 6, P < 0.001) but did not significantly affect responses to glucose (before; 311+/-270%; during: 284+/-206%; n = 5). The mean acute insulin response after isoproterenol in the diabetic group was significantly elevated over basal levels (152+/-74%; n = 10, P < 0.001) but the response after glucose was not (- 11+/-11%). These data suggest that insulin responses to glucose in normal subjects are mediated by specific pancreatic glucose receptors which are independent from beta adrenergic receptors and that abnormal glucose-induced insulin secretion in diabetics is due to defects within glucose receptors and not beta adrenergic receptors as has been previously hypothesized.

Chapter VIII DIABETES MELLITUS, CARBOHYDRATE TOLERANCE AND EARLY INSULIN RESPONSE TO AN INTRAVENOUS GLUCOSE INJECTION IN A POPULATION SAMPLE OF WOMEN AND IN WOMEN WITH ISCHAEMIC HEART DISEASE

Abstract. The prevalence of manifest diabetes mellitus was significantly higher in women with myocardial infarction than in women in the general population. This was not the case for women with angina pectoris or ECG changes suggestive of ischaemic heart disease. There were no differences in fasting blood glucose or fasting serum insulin values between non‐diabetic women who had angina pectoris or who had had myocardial infarction and non‐diabetic women in the general population. Intravenous glucose injection did not reveal significant differences in glucose tolerance or mean values of early insulin response. However, there was an over‐representation of women with a very low early insulin response in the women who had had myocardial infarction.

Studies on carbohydrate metabolism in penguins ( Pygocellis papua)

The present experiment was performed in the Antartic continent at 64° 53′ S Lat; 62° 53′ W Long. Gento penguins ( Pygocellis papua) were studied after 24–48 hr and 6–12 days of starvation. After intravenous injection of glucose (1 g/kg), the blood sugar levels remained elevated for periods up to 10 hr. Starvation did not affect the glucose tolerance curve. The pancreatic function was tested using hipoglycemic agents. Tolbutamide (200 mg/kg) and chlorpropamide (100 mg/kg) did not induce any changes in the blood sugar level. Inmunoreactive serum insulin level was about 40 μU/ml after 24–48 hr of starvation. This value fell to about 10 μU/ml after 12 days of starvation. Intravenous glucose injection was without significant effect in insulin secretion.

The Incorporation of Fructose and Glucose, Given Intravenously, Into the Serum Lipids of Baboons

(1) in both male and female baboons, the &lt;sup&gt;14&lt;/sup&gt;C specific activity in the serum glycerides is greater following the intravenous injection of about 10 Ci fructose-U-&lt;sup&gt;14&lt;/sup&gt;Cthan after the same amount of radio-glucose. It is argued that this indicates a greater incorporation of &lt;sup&gt;14&lt;/sup&gt;C-fructose into serum glycerides. (2) The serum glucose concentrations of male baboons rise steadily over a 5-hour period following the injection of fructose. No such rise is found in the serum glucose concentrations of the female baboons. (3) The incorporation of &lt;sup&gt;14&lt;/sup&gt;C of fructose into serum glycerides is significantly greater in male baboons than in females. (4) After the intravenous injection of either glucose or fructose in both male and female baboons, there is a fall in serum glyceride concentration, reaching a nadir at 30 min following the injection.

Glucose kinetics and fatty acids in dogs on matched insulin infusion after glucose load

The endogenous insulin secretion of five conscious, depancreatized fasted dogs was replaced by intraportal insulin infusions of 192–263 μU/kg per min to establish whether the release of extra insulin is essential during a glucose tolerance test. Infusion rate of insulin about 200 μU/kg per min was considered to be near basal since it maintained unchanged glucose turnover as well as the plasma concentrations of glucose, free fatty acids (FFA), and immunoreactive insulin (IRI). The glucose tolerance tests of these dogs were then compared to those of six normal and six partially depancreatized dogs. It was found that after an intravenous injection of glucose the depancreatized dogs maintained on portal or peripheral insulin infusion had a 50% decreased exponential slope of the plasma glucose concentration versus time (k). In contrast to the normal dogs, their plasma glucose levels were still elevated but declining 60–140 min after the glucose load. The declining glucose levels were associated with an increased disappearance rate (R d), but there was no inhibition of the rate of glucose production. FFA decreased only slightly after the glucose load. Five days after partial pancreatectomy the dogs reacted to a glucose injection with a lesser output of insulin than normal dogs. Their homeostatic deficiencies with respect to glucose kinetics and FFA response were less marked than in depancreatized dogs maintained on matched insulin infusion. It was concluded that a prompt release of extra insulin is an essential part of the normal homeostatic mechanisms that determine a glucose tolerance curve.

Investigation of some theoretical models relating the concentrations of glucose and insulin in plasma

In this survey 24 possible theoretical models for the regulation of plasma glucose concentration by plasma insulin concentration have been proposed and tested. A set of data, consisting of plasma glucose concentrations at various times after an intravenous injection of glucose, was selected from the literature. An attempt was made to fit each model to the chosen data using a digital computer program and ten of these were successful. The behaviour of these ten models under different experimental conditions was compared, using a simulation technique, with further published data. At this stage six models were consistent with a steady state at the start or the end of an experiment, but only three were reasonably good at predicting all aspects of the chosen experiments. One was particularly good. Two other sets of data were taken from the literature and the six best models were fitted in order to calculate replicate values of the physiological parameters.

Functional nature of the polysomes as indicated by the influences of insulin-glucose and adrenalectomycortisol on rat liver polysomes in vivo

The disaggregated liver polysomes of the fasted rat can be restored by an intravenous injection of glucose and insulin. This treatment also causes an increase in amino acid incorporation in vivo. Adrenalectomized rats have disaggregated liver polysomes and decreased amino acid incorporation in vivo. Treatment with cortisol hemisuccinate restores the polysomes, but causes a further decrease in amino acid incorporation in vivo. These results are interpreted to mean that insulin acts on some insulin-sensitive sites in the liver, permitting glucose to preferentially change the polysome steady-state condition by affecting the relative rates of polysome breakdown (protein synthesis) and ribosomal activation to polysomes. The functional nature of the polysome is described as being a reservoir of active ribosomes that can be, but are not necessarily, used for protein synthesis.

Diabetes in patients treated with asparaginase.

In 5 patients treated with L‐asparaginase, plasma insulin response to intravenous glucose injection was measured by radioimmunoassay. Two of the patients developed a diabetic state (2 and 4 days) after a single dose of L‐asparaginase, while a third patient developed diabetes 2 days after the fourth dose of L‐asparaginase. Plasma insulin was not detectable by radioimmunoassay during the diabetic state in each of them. The normal pattern of insulin response returned completely in one of the 3 patients within 23 days, whereas suboptimal response persisted for 2 weeks and 9 months in the remaining 2 patients. The two remaining patients were studied prior to and 6 days after a single dose of L‐asparaginase; neither developed a diabetic state.

Carbohydrate metabolism in the primate fetus: Studies of the placental gradient for glucose and insulin in response to intravenous saline, glucose, and glucagon injections

Plasma insulin and blood glucose were measured in the mother and fetus of Macaca mulatta at 150 to 156 days of gestation. The physiologic acute preparation included placement of polyvinyl catheters within the inferior vena cava of both mother and fetus under pentobarbital anesthesia. In 27 fasting maternal-fetal paired samples, there was a significant correlation for glucose but none for insulin. With intravenous fetal injections the data show that the fetal pancreatic beta cells are unresponsive to saline and glucose and, apparently, unresponsive to glucagon.

Study of the Glycoregulation in the Obese Child

The glucose kinetics are modified in obese children. This fact does not appear after an intravenous load of glucose, but it may be disclosed when the penetration of glucose into the cells is forced either by the oral administration of a large amount of glucose or by the neous intravenous injection of glucose and of a supramaximal dose of insulin. The insulin response of the pancreas to oral glucose and intravenous tolbutamide is not significantly increased in obese children. The rise of the fasting level of free fattyacids is significant, but the response of adipose tissue to glucose is comparable to that observed in normal children.

Insulin levels in thyrotoxicosis and primary myxoedema: response to intravenous glucose and glucagon.

Glucose disappearance, insulin-like activity (ILA) and serum immunoreactive insulin (IRI) were studied after intravenous injection of glucose or glucagon in patients suffering from thyrotoxicosis or primary myxoedema. A group of normal subjects was also investigated. Glucose disappearance rate appeared to be normal in hyperthyroid, and markedly reduced in hypothyroid subjects. Fasting ILA levels were significantly higher than normal in myxoedema, and lower than normal in thyrotoxicosis. On the other hand, fasting IRI levels were higher than normal in myxoedema but normal in thyrotoxicosis. After glucose administration ILA in myxoedema remained at higher values than in thyrotoxicosis at any time of the study; in myxoedema, peak ILA levels were reached later than in thyrotoxicosis; peak IRI levels of similar magnitude were reached slightly earlier than normal in thyrotoxicosis, and later in myxoedema; in the latter condition, elevated IRI levels were observed for a longer period than in either euthyroidism or hyper-thyroidism. During this test the insulingogenic index showed only slight changes in normal and in thyrotoxic subjects, whereas it increased significantly up to 60 min in myxoedema. The data indicate that the reduced glucose utilization in hypothyroidism is not due to insulin deficiency, but rather to insulin resistance. It also seems possible that thyroid function influences the time of maximal insulin response to intravenous glucose administration. After glucagon injection, the increase in blood glucose was lower and shorter than normal in thyrotoxicosis; it was initially somewhat slower, but later higher and more sustained than normal, in myxoedema. The smaller increment in blood glucose in the former condition is probably connected with reduced glycogen stores. ILA response was very high and well sustained in myxoedema, whereas it was moderate and shortlasting in thyrotoxicosis. IRI response was higher than normal in hypothyroid subjects, and lower than normal in thyrotoxic subjects. No difference in the time required for maximal response was observed among the three groups.

Insulin-secreting capacity in newborn infants.

Response of plasma insulin to intravenous glucose injection in the umbilical vein and artery were studied in normal newborn infants. Normal newborn infants produce a small rise in circulating insulin levels in response to hypergly-cemia despite a delayed excessive insulin levels in the umbilical vein. The relatively poor response of the neonatal pancreatic beta cells to glucose was confirmed.

The contribution of different organs and tissues of the rat to assimilation of glucose.

After intravenous injection of glucose, 750 mg/kg, together with a tracer dose of [U-14C] glucose, into fasted, adult white rats, the following percentages of the administered dose were found in whole organs and tissues: 1. after five minutes: skeletal muscle 30.3, skin 28.1, blood 13.1, adipose tissue 10.7, liver 8.9. 2. Forty minutes after injection the corresponding values were: 35.0, 11.1, 5.0, 4.6 and 9.4%. Expired 14CO2 was negligible after five minutes: after 40 min it comprised 8% of the total dose administered. — After intragastric administration of 1500 mg/kg of glucose given with a tracer dose of [U-14C] glucose under the same experimental conditions, the alimentary tract contained, after 15, 90 and 180 min, 60.5, 14.8 and 8.4% respectively of the total 14C dose given. At these times the liver contained 2.9, 10.7 and 15.0%; skin contained 7.5, 7.1 and 5.4%; adipose tissue 2.0, 3.8 and 3.5%, and expired 14CO2 0.4, 11.8 and 31.3% respectively. Details of the uptake of 14C glucose by other organs and tissues are given, and a balance sheet for the injected material is attempted.

HUMAN FETAL INSULIN RESPONSE AFTER ACUTE MATERNAL GLUCOSE ADMINISTRATION DURING LABOR

The effects of an intravenous injection of glucose (0.5 gm/kg) on the concentration of maternal and fetal serum glucose, insulin, and free fatty acids (FFA) were determined in six women in labor. The maternal hyperglycemia was accompanied by a rapid increase in maternal serum insulin concentration and a fall in maternal FFA levels. Fetal serum insulin and FFA values showed either no changes or a markedly attenuated response despite fetal hyperglycemia. These results are consistent with a diminished responsiveness of the human fetal pancreas to alterations in glucose concentrations in the hour prior to birth.

Studies on the mechanism of xylitol-induced insulin secretion in dogs. Effect of its infusion into the pancreatic artery, and the inhibition by epinephrine and diazoxide of xylitol-induced hyperinsulinaemia.

The effect of infusion of small doses of xylitol into the pancreatic artery upon insulin release was studied in anaesthetized dogs, in order to decide whether the strong insulin-releasing effect of xylitol in dogs is mediated by a direct action of xylitol upon the islets or indirectly by some of its metabolites. Xylitol or glucose was infused at 0.5–1.0 mg/kg · min either into the femoral vein or into the superior pancreaticoduodenal artery, and the changes in plasma insulin were measured in the superior pancreaticoduodenal vein. Infusion into the pancreatic artery always resulted in a sharp increase in insulin release, whereas intravenous infusion caused no or little increase. Infusion of xylitol into the superior pancreaticoduodenal artery produced a prompt increase in plasma insulin in the superior pancreaticoduodenal vein but not in the splenic vein. These data suggest that xylitol has a direct stimulatory effect upon islet cells. — During intravenous infusion of epinephrine (1.0 μg/kg. min), plasma insulin did not increase despite intravenous administration of glucose or xylitol (0.4 g/kg). There was a rebound rise of plasma insulin after cessation of epinephrine infusion. Plasma insulin responses to intravenous injection of glucose or xylitol (0.4 g/kg) were inhibited also by the intravenous infusion of diazoxide (0.2 mg/kg · min), but this was somewhat variable among individual dogs. The suppression by epinephrine or diazoxide of both glucose and xylitol-induced hyperinsulinaemia may suggest that there is some common mechanism between the insulin-releasing effects of glucose and xylitol.