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Biomedical subjects

I Lager

Publications and source records attributed to I Lager.

At least 37 records · Page 2Linked to original sources
PubMed1987

Insulin resistance in type 1 (insulin-dependent) diabetes following hypoglycaemia--evidence for the importance of beta-adrenergic stimulation.

The insulin effect, evaluated with the euglycaemic clamp technique, was studied before and after hypoglycaemia in 7 patients with Type 1 (insulin-dependent) diabetes. Following an initial 2 h clamp (clamp I) hypoglycaemia was induced and 2 h later a second clamp (clamp II), identical to the former, was performed. Each subject was studied twice; during infusion with saline (placebo) or propranolol. Glucose production and disposal were studied with the 3(3H)glucose technique. During placebo infusion, hypoglycaemia elicited an insulin resistance leading to approx. 50% reduction in the steady state glucose infusion rate during clamp II as compared to clamp I (clamp I 2.58 +/- 0.32, clamp II 1.26 +/- 0.08 mg . kg-1 . min-1, p less than 0.02). The insulin resistance was prevented by infusing propranolol (clamp I 2.29 +/- 0.29, clamp II 2.85 +/- 0.56 mg . kg-1 . min-1). The posthypoglycaemic insulin resistance was due to a less pronounced insulin effect on both glucose production (clamp I 0.29 +/- 0.21, clamp II 0.86 +/- 0.19 mg . kg-1 . min-1, p less than 0.05) and glucose utilisation (clamp I 2.84 +/- 0.26, clamp II 2.13 +/- 0.23 mg . kg-1 . min-1, p less than 0.05). The insulin resistance on both glucose production and utilisation was prevented by propranolol. Thus, the present study demonstrates that hypoglycaemia elicits a prolonged insulin resistance which is due to a less pronounced effect of insulin to both inhibit splanchnic glucose production and to stimulate peripheral glucose utilisation. The insulin resistance is due to beta-adrenergic stimulation and can be prevented by propranolol.

Adult↗
PubMed1987

Early posthypoglycemic insulin resistance in man is mainly an effect of beta-adrenergic stimulation.

The insulin effect following hypoglycemia was studied with the euglycemic clamp technique in seven healthy subjects. Following an initial euglycemic clamp hypoglycemia was induced and after glucose recovery a second clamp was performed. Glucose production (Ra) and utilization (Rd) were studied with [3-3H]glucose. Each subject was studied four times; during infusion of placebo, propranolol, somatostatin, and a control study where hypoglycemia was prevented. Hypoglycemia induced an insulin resistance with a lower steady state glucose infusion rate following the hypoglycemia during placebo as compared to the control study (2.5 +/- 0.5 and 4.8 +/- 1.0 mg/kg min, respectively, P less than 0.05). The insulin resistance was due to an attenuated insulin effect on both inhibition of Ra (impaired by 37%) and stimulation of Rd (impaired by 61%). The insulin-antagonistic effect was completely prevented by propranolol but only partly by somatostatin. Thus, early posthypoglycemic insulin resistance (2.5-3.5 h after hypoglycemia) is a sustained effect mainly due to beta-adrenergic stimulation.

Adult↗
PubMed1986

Studies on the insulin-antagonistic effect of catecholamines in normal man. Evidence for the importance of beta 2-receptors.

The insulin-antagonistic effect of adrenaline was studied in seven healthy subjects with the euglycaemic clamp technique using two insulin infusion rates (40 and 1200 mU X (m2)-1 min-1). The adrenergic receptor mediating the adrenaline effect was characterized by concomitant infusion of propranolol (beta 1 + beta 2-antagonist) or metoprolol (beta 1-antagonist). Each subject was studied four times (placebo, adrenaline, adrenaline + propranolol, adrenaline + metoprolol). Glucose turnover was measured with D(3-3H)-glucose. Similar plasma insulin levels were reached in all studies with the two insulin infusion rates (mean; placebo 51 +/- 3 and 7421 +/- 337 mU/l respectively). Glucose production was completely inhibited by the low insulin level during placebo infusion. Adrenaline antagonized this effect so that a significant glucose production was seen at the low but not at the high insulin level. Propranolol, but not metoprolol, reversed this insulin-antagonistic effect of adrenaline. Glucose utilization increased from 2.53 +/- 0.17 to 7.28 +/- 0.88 mg X kg-1 X min-1 during placebo when the insulin levels were increased from 4 +/- 0.3 to 51 +/- 3 mU/l. Increasing the insulin levels 150-fold to approximately 7500 mU/l only doubled the glucose utilization (14.68 +/- 1.14 mg X kg-1 X min-1). Adrenaline induced a pronounced inhibition of glucose utilization at both insulin levels (78% and 37% inhibition respectively). Propranolol, but not metoprolol, prevented this effect of adrenaline. Thus, physiological adrenaline levels exert a pronounced insulin-antagonistic effect which is mediated by beta 2-receptor stimulation. The inhibitory effect on glucose uptake is maintained even at high insulin levels when hepatic glucose production is completely abolished.

Adult↗
PubMed1985

Glucagon release and glucose counter-regulation during hypoglycaemia. Modifying effect of the previous glucose level.

The importance of a short-term elevation of the ambient glucose level for the release of counter-regulatory hormones and the glucose recovery rate during a subsequent hypoglycaemia was studied in healthy subjects. Hypoglycaemia was induced with insulin infusion after a previous 80 min of euglycaemic (E: 5 mmol/l) or hyperglycaemic (H: 15 mmol/l) glucose clamp. By infusing insulin during the euglycaemic clamp similar levels were reached during both glucose clamps. The same level of hypoglycaemia was reached in both studies (E: 1.5 +/- 0.1, H: 1.5 +/- 0.2 mmol/l) and the insulin levels were also similar both at glucose nadir and during the recovery period. In spite of this, both the mean glucagon levels at nadir at the mean individual maximal increase were significantly lower after the hyperglycaemic clamp (E: 101 +/- 25, H: 54 +/- 7 pg/ml, P less than 0.05). The glucose recovery rate was also significantly impaired following the hyperglycaemic clamp. The results show that a short-term elevation of the ambient glucose level impairs the glucagon release during a subsequent hypoglycaemia. This finding may be of importance for the development of the blunted glucagon release in response to low glucose levels in diabetics.

Adult↗
PubMed1984

Improved but not normalized glucose counter-regulation during glucagon infusion in Type 1 (insulin-dependent) diabetes.

Glucose counter-regulation during insulin-induced hypoglycaemia was studied in Type 1 diabetic patients without evidence of autonomic neuropathy and compared with that of a non-diabetic control group. The glucose recovery rate following hypoglycaemia was delayed in the diabetic compared with the control subjects and this was most pronounced for the initial, rapid phase of glucose increase (glucose increase in 15 min, control: 1.1 +/- 0.1 versus 0.4 +/- 0.1 mmol/l; p less than 0.01). The release of glucagon during hypoglycaemia was blunted in the diabetic patients (maximal plasma levels, control: 148 +/- 25 versus 70 +/- 10 pg/ml; p less than 0.01). The adrenaline levels were also lower compared with the control subjects (maximal plasma levels, control: 7.23 +/- 1.21 versus 3.27 +/- 0.87 nmol/l; p less than 0.05). To evaluate the importance of the blunted glucagon response for the delayed glucose compensation, glucagon was infused during the hypoglycaemia. Overall glucose recovery rate was improved but did not return to normal. Consequently impaired glucagon release in the diabetic patients cannot alone explain impaired glucoregulation; the lower adrenaline levels and/or an effect of the previous glucose levels per se on hepatic glucose production are probably also of importance.

Adult↗
PubMed1983

Reversal of insulin resistance in type I diabetes after treatment with continuous subcutaneous insulin infusion.

Insulin responsiveness was studied with the euglycaemic glucose clamp technique in seven patients with type I diabetes and in six control subjects matched for age and weight. The glucose disposal rate was significantly reduced in the diabetic subjects when they were receiving conventional insulin treatment compared with the control group, showing insulin resistance in the diabetics. The diabetic patients were again studied after eight days of intensified metabolic control achieved with continuous subcutaneous insulin infusion. During the infusion a more physiological insulin regimen was used compared with their regular treatment, less of the total insulin dose being given as continuous infusion and more as bolus doses before meals. The insulin resistance in the diabetics was largely reversed after this improved metabolic control. Dose response studies showed an increased glucose disposal rate at all plasma insulin concentrations, including the maximum insulin concentration, indicating a predominant effect of the continuous infusion regimen at the postreceptor level. The improved insulin effect seen with continuous subcutaneous insulin infusion could be due to the improved metabolic control achieved as well as the more physiological regimen.

Adult↗
PubMed1983

Adrenergic blockade and hypoglycaemia.

The metabolic effects of beta-adrenoceptor blocking agents during hypoglycaemia in patients prone to hypoglycaemia are of interest as diabetics are often treated with these drugs because of hypertension or angina pectoris. Compared with non-diabetics these patients also have impaired glucose compensation after hypoglycaemia, partly secondary to deficient release of glucagon. This makes the diabetics more dependent on adrenergic mechanisms to recover from low blood glucose concentrations. Non-selective beta-adrenoceptor blockade (propranolol) significantly impairs the glucose recovery rate after hypoglycaemia in insulin dependent diabetics, whereas selective beta-adrenoceptor blockade (metoprolol) does not have this side effect. The mechanism of the effect of propranolol is probably an attenuation of the gluconeogenesis secondary to deficient release of the important gluconeogenic substrates lactate and glycerol.

Adrenergic beta-Antagonists↗
PubMed1983

Insulin sensitivity and responsiveness in vitro and in vivo.

Insulin resistance is evident in several clinical conditions such as obesity, diabetes type II, hypercortisolism. The mechanisms behind this resistance at the level of the target cell can be evaluated with measurements of insulin sensitivity with techniques both in vitro and in vivo. In this review various techniques used to evaluate insulin action are discussed and also some clinical conditions associated with insulin resistance.

Blood Glucose↗
PubMed1983

Effects of anti-hypertensive therapy on serum lipoproteins. Treatment with metoprolol, propranolol and hydrochlorothiazide.

The effects of metoprolol, propranolol and hydrochlorothiazide on lipoprotein metabolism were studied in three different but comparable groups of middle-aged men with previously untreated hypertension (n=10, n=10, and n=11, respectively). All three treatments were associated with an increase in serum triglyceride and VLDL-cholesterol levels. Propranolol treatment was associated with consistent and significant decreases in HDL-cholesterol, apoA-I and A-II levels, whereas these changes during the other treatments were neither significant nor consistent. An increase in adipose tissue LPL-activity and a decrease in serum free fatty acids were seen in the propranolol treatment group. Significant changes were not observed in glucose tolerance or catecholamine excretion. The blood pressure reduction was similar in the three groups. The design of the present study was in some important respects different from that of others. This may help to explain why we found a difference between the two beta-blockers in our study.

Adipose Tissue↗
PubMed1982

Beta-adrenoceptor blockade and recovery from hypoglycaemia in diabetic subjects: normalization after lactate and glycerol infusions.

1. Previous studied have shown that non-selective beta-adrenoceptor blockade attenuates the blood glucose recovery rate after hypoglycaemia in type I diabetes. Apart from possible effects on hepatic glycogenolysis propranolol also inhibits the release of the important gluconeogenic substrates lactate and glycerol. 2. To determine whether the effect of non-selective beta-adrenoceptor blockade on glucose recovery could be associated with diminished availability of gluconeogenic substrates, lactate and glycerol were infused during hypoglycaemia in four insulin-dependent diabetic patients. Comparisons were made of the blood glucose recovery on placebo, propranolol and propranolol combined with the infusion. 3. The blood glucose recovery rate after hypoglycaemia was less on propranolol than with placebo but was significantly improved and not different from placebo when propranolol treatment was combined with lactate and glycerol infusions. Thus, at least for type I diabetic patients, in whom gluconeogenesis is proportionally greater than in healthy subjects, non-selective beta-adrenoceptor blockade attenuates the glucose recovery rate from hypoglycaemia mainly by reducing the availability of gluconeogenic substrates.

Adult↗
PubMed1982

Importance of glucose control for the recovery from hypoglycemia in insulin-dependent diabetics.

To evaluate whether the delayed glucose compensation after hypoglycemia in insulin-dependent diabetics was associated with their elevated blood glucose levels, five diabetic patients were studied before and after a period of intensified metabolic control. The glucose recovery rate was found to be improved after better diabetic control. This influence seems to be better reflected by the mean diurnal level rather than the glucose level immediately before hypoglycemia. The improvement occurred despite the same or lower levels of the important glucocompensatory hormones. These results show the importance of antecedent metabolic control for glucose compensation after hypoglycemia.

Adult↗
PubMed1981

Hypoglycemic symptoms in insulin-dependent diabetics. A prospective study of the influence of beta-blockade.

Hypoglycemic attack rate, duration and symptomatology were studied in five insulin-dependent diabetics with borderline hypertension all of whom were prone to hypoglycemia. They were treated in a double-blind, cross-over fashion with the cardioselective beta 1-blocking agent metoprolol and placebo. The treatment period on each drug lasted at least three months. No treatment-associated differences in attack rate and duration of hypoglycemic attacks were recorded. Slight, but no severe masking of hypoglycemic symptoms was recorded in one patient on metoprolol. It is concluded that cardioselective beta 1-blocking agents can be used by insulin-dependent diabetics. However, until further direct experience has been gained caution should be exercised in treating patients with obvious clinical signs of autonomic neuropathy with these drugs.

Adult↗
PubMed1980

Effect of beta-blockade on hormone release during hypoglycaemia in insulin-dependent diabetics.

Previous studies have shown that non-selective, but not beta 1-selective, beta-blockers prolong the duration of hypoglycaemia. In order to elucidate possible mechanisms key hormones as well as alanine levels were measured following insulin-induced hypoglycaemia in 7 insulin-dependent diabetics. The subjects were treated with placebo, propranolol (a non-selective agent) or metoprolol (a beta 1-selective drug) prior to the hypoglycaemia. Treatment with either beta-blocking agent led to higher levels of adrenaline, glucagon, cortisol and growth hormone during hypoglycaemia as compared to those reached on placebo. The adrenaline levels during placebo treatment in response to hypoglycaemia appeared less in these diabetics than that previously reported for non-diabetics. The plasma alanine levels were similar and decreased following insulin administration irrespective of type of treatment. The data show that the release of key glycogenolytic and gluconeogenic hormones is not inhibited by beta-blockers during hypoglycaemia but is instead augmented or, possibly, hormonal clearance is reduced. It is suggested that the delayed recovery in blood glucose on a non-selective beta-blocker is partly due to lack of gluconeogenic substrates such as lactate and glycerol.

Adrenergic beta-Antagonists↗
PubMed1979

Effect of cardioselective and non-selective beta-blockade on the hypoglycaemic response in insulin-dependent diabetics.

The response to intravenous insulin was studied in seven diabetics after a dose of placebo, propranolol (40 mg), or metoprolol (50 mg). Two of the seven subjects also had a week's course of each of the same agents taken three times daily. Neither of the beta-blockers potentiated the effect of insulin as judged by the rate of reduction in blood-glucose. However, blood-glucose recovery was reduced significantly by propranolol, but not significantly by metoprolol. Propranolol caused severe bradycardia and raised diastolic blood-pressure during hypoglycaemia; these effects were milder with metoprolol. Propranolol inhibited the free-fatty-acid levels after hypoglycaemia to a greater extent than did metoprolol. The results strongly suggest that propranolol (and presumably other non-selective beta-blockers) is hazardous in subjects prone to hypoglycaemia. When diabetics require beta-blockade a cardioselective beta 1-blocker should be used.

Adult↗