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Biomedical subjects

A Vaag

Publications and source records attributed to A Vaag.

67 records · Page 4Linked to original sources
PubMed1991

Effect of the antilipolytic nicotinic acid analogue acipimox on whole-body and skeletal muscle glucose metabolism in patients with non-insulin-dependent diabetes mellitus.

Increased nonesterified fatty acid (NEFA) levels may be important in causing insulin resistance in skeletal muscles in patients with non-insulin-dependent diabetes mellitus (NIDDM). The acute effect of the antilipolytic nicotinic acid analogue Acipimox (2 X 250 mg) on basal and insulin-stimulated (3 h, 40 mU/m2 per min) glucose metabolism was therefore studied in 12 patients with NIDDM. Whole-body glucose metabolism was assessed using [3-3H]glucose and indirect calorimetry. Biopsies were taken from the vastus lateralis muscle during basal and insulin-stimulated steady-state periods. Acipimox reduced NEFA in the basal state and during insulin stimulation. Lipid oxidation was inhibited by Acipimox in all patients in the basal state (20 +/- 2 vs. 33 +/- 3 mg/m2 per min, P less than 0.01) and during insulin infusion (8 +/- 2 vs. 17 +/- 2 mg/m2 per min, P less than 0.01). Acipimox increased the insulin-stimulated glucose disposal rate (369 +/- 49 vs. 262 +/- 31 mg/m2 per min, P less than 0.01), whereas the glucose disposal rate was unaffected by Acipimox in the basal state. Acipimox increased glucose oxidation in the basal state (76 +/- 4 vs. 50 +/- 4 mg/m2 per min, P less than 0.01). During insulin infusion Acipimox increased both glucose oxidation (121 +/- 7 vs. 95 +/- 4 mg/m2 per min, P less than 0.01) and nonoxidative glucose disposal (248 +/- 47 vs. 167 +/- 29 mg/m2 per min, P less than 0.01). Acipimox enhanced basal and insulin-stimulated muscle fractional glycogen synthase activities (32 +/- 2 vs. 25 +/- 3%, P less than 0.05, and 50 +/- 5 vs. 41 +/- 4%, P less than 0.05). Activities of muscle pyruvate dehydrogenase and phosphofructokinase were unaffected by Acipimox. In conclusion, Acipimox acutely improved insulin action in patients with NIDDM by increasing both glucose oxidation and nonoxidative glucose disposal. This supports the hypothesis that elevated NEFA concentrations may be important for the insulin resistance in NIDDM. The mechanism responsible for the increased insulin-stimulated nonoxidative glucose disposal may be a stimulatory effect of Acipimox on glycogen synthase activity in skeletal muscles.

Biological Transport↗
PubMed1991

Effects of hyperglycaemia on kidney function, atrial natriuretic factor and plasma renin in patients with insulin-dependent diabetes mellitus.

In normoalbuminuric patients with insulin-dependent diabetes mellitus, plasma atrial natriuretic factor (ANF), cyclic GMP and active renin and the renal clearances of [99Tcm]-diethylenetriaminepentaacetic acid (DTPA) lithium and sodium were studied on a hyperglycaemia day and a euglycaemia day. Baseline euglycaemia was achieved by an overnight variable insulin infusion, which during study days was fixed at the rate necessary to maintain euglycaemia in the morning. After a baseline euglycaemic clearance period of 90 min, measurements were repeated in a new 90-min period beginning 150 min later. On the hyperglycaemia day i.v. infusion of 20% glucose was started at the end of the euglycaemic baseline period, increasing blood glucose (5.3 +/- 1.3 vs 12.1 +/- 1.2 mmol l-1, p less than 0.01). On the euglycaemia day blood glucose declined (5.1 +/- 1.0 vs 4.2 +/- 1.0 mmol l-1, p less than 0.02). Glomerular filtration rate (GFR) was unchanged by acute hyperglycaemia (127 +/- 16 vs 129 +/- 24 ml min-1, NS), but nearly normalized during maintained euglycaemia on the euglycaemia day (124 +/- 17 vs 105 +/- 16 ml min-1, p less than 0.01). When comparing the hyperglycaemic study period with the similarly timed period on the euglycaemia day, GFR was elevated by hyperglycaemia (129 +/- 24 vs 105 +/- 16 ml min-1, p less than 0.01), while the renal clearances of lithium and sodium were similar. Consequently, the calculated absolute proximal reabsorption rate of sodium and water was elevated during hyperglycaemia. Hyperglycaemia reduced the slight decline in plasma concentrations of ANF and cyclic GMP observed on the euglycaemia day. Active renin, glucagon and plasma osmolality were unchanged. In conclusion, marked changes in glomerular filtration rate are induced by changes in blood glucose concentration, but the effect is delayed and thus not directly related to renal tubular transport of glucose. Hyperglycaemia does not affect renal clearances of lithium and sodium, while proximal tubular reabsorption is markedly stimulated. These changes are not related to changes in ANF, renin, glucagon or plasma osmolality.

Adult↗
PubMed1990

Expression of insulin regulatable glucose transporters in skeletal muscle from type 2 (non-insulin-dependent) diabetic patients.

A prominent feature of Type 2 (non-insulin-dependent) diabetes mellitus is the inability of insulin to appropriately increase the transport of glucose into target tissue. In adipocytes from individuals with Type 2 diabetes, insulin resistance has been shown to be associated with a depletion of glucose transporters. Similarly, streptozotocin induced diabetes causes a diminished expression of the insulin regulatable glucose transporter in rat adipocytes. The expression of this glucose transporter isoform has not yet been investigated in muscle tissue from patients with Type 2 diabetes. We have measured the content of the insulin regulatable glucose transporter in a vesicular fraction isolated from muscle biopsies from fasting individuals with Type 2 diabetes and control subjects, and we found that the number of the insulin regulatable glucose transporters expressed in skeletal muscle was unaffected by Type 2 diabetes (0.208 vs 0.205, arbitrary units, p greater than 0.5, control subjects and diabetic patients). Thus, the decreased glucose disposal in Type 2 diabetes is not associated with a diminished number of insulin regulatable glucose transporters.

Animals↗
PubMed1990

Impairment of glucose tolerance: mechanism of action and impact on the cardiovascular system.

Macrovascular disease, especially coronary heart diseases, have been found to be linked to glucose intolerance. Insulin resistance in respect to glucose uptake in peripheral tissues seems to play an important role in the development of glucose intolerance, since subjects with coronary heart disease mainly are hyperinsulinemic. Insulin resistance may induce not only glucose intolerance but also hypertension, obesity, and dyslipoproteinemia (high very low-density lipoprotein and low high-density lipoprotein values), all variables that add to the risk of coronary heart disease. On the basis of these findings, a new syndrome has been postulated-syndrome X. This syndrome may be caused by inherited insulin resistance in skeletal muscles, and secondary to that arterial hypertension, obesity, and dyslipoproteinemia may develop. Insulin resistance in noninsulin-dependent diabetic persons and in hypertensive subjects is located in skeletal muscles, where insulin's ability to promote nonoxidative glucose metabolism is reduced. The key enzyme in this pathway, glycogen synthase, is proposed as the causal defect responsible for the insulin resistance state, at least in noninsulin-dependent diabetic patients. The pill (sex steroids) may induce a clinical situation that is similar to syndrome X. However, it is important to emphasize that many more studies are needed to substantiate these hypothetical mechanisms behind coronary heart disease.

Blood Glucose↗
PubMed1990

65 zinc absorption in patients with insulin-dependent diabetes mellitus assessed by whole-body counting technique.

The gastrointestinal absorption of zinc was measured in patients with insulin-dependent diabetes mellitus. The concentration of zinc in serum was similar to healthy individuals. However the urinary excretion rate of zinc relative to the creatinine excretion, was approximately doubled (p less than 0.001) in the diabetics. The absorption of 65Zn tended to be lower in diabetics, but did not reach the level of statistical significance (retention percent 30.6 versus 42.6 (p greater than 0.10). A hypothesis of intracellular zinc depletion with time in insulin-dependent diabetics is proposed.

Absorption↗
PubMed1990

Ouabain inhibition of the sodium-potassium pump: estimation of ED50 in different types of human leucocytes in vitro.

1. We examined the effect of ouabain on the Na(+)-K+ pump of intact mononuclear leucocytes and polymorphonuclear leucocytes by using the radioactive potassium analogue, 86rubidium, as a tracer and measuring the cellular uptake of K+ (86Rb+). Na(+)-K+ pump activity was determined as the cellular uptake of K+ (86Rb+) that is sensitive to ouabain, 10(-5) mol l-1. 2. Dose-response curves for inhibition of the Na(+)-K+ pump were obtained after exposure of the cells to various concentrations of ouabain for 2.5 h when the level of pump inhibition was considered to be at steady state. 3. The ED50 of ouabain for the effect on the Na(+)-K+ pump was estimated to be 3 X 10(-9) mol l-1 in the absence of potassium. In the presence of potassium, 3 and 6.5 X 10(-3) mol l-1, it was increased by factors of 10 and 45 respectively. In the presence of potassium, 4 X 10(-3) mol l-1, the ED50 was similar but somewhat higher when determined in an artificial medium (Ringer solution) than when determined in autologous plasma. 4. The ED50 values observed in the present study were very similar to KD values reported in the literature on ligand binding of tritiated ouabain to the same types of human leucocytes.

Biological Transport, Active↗
PubMed1990

Intramuscular versus subcutaneous injection of unmodified insulin: consequences for blood glucose control in patients with type 1 diabetes mellitus.

Using the perpendicular injection technique lean diabetic patients may often inject insulin intramuscularly (IM). Guided by ultrasound measurements of the subcutaneous (SC) thickness of the thigh, the aim of the present study was to re-evaluate the absorption kinetics of unmodified insulin from IM and SC injection sites and to evaluate the consequences of IM injection of unmodified insulin for blood glucose control in Type 1 diabetic patients. T50% values (time until 50% of the injected insulin is absorbed from the injection site) of SC injected, radioactively labelled, human unmodified insulin (125I-Actrapid) were 338 +/- 13 (+/- SE) min, 289 +/- 27 min, and 287 +/- 27 min during rest, light physical activity, and strenuous exercise, respectively. Intramuscularly injected unmodified insulin was absorbed faster, T50% 232 +/- 20 min, 113 +/- 13 min, and 112 +/- 5 min during the same levels of physical activity in the same order. When unmodified insulin (Actrapid) was given IM 30 min before breakfast, lunch, and dinner together with intermediate-acting insulin (Protaphane) SC at 2200 h, a more physiological profile of plasma free insulin and a more stable blood glucose profile was obtained than with SC administration into the thigh. The coefficient of variation of blood glucose concentration during the study (3 days each route) was lower with IM than with SC injection of unmodified insulin (33 +/- 4 vs 43 +/- 3%, p less than 0.01). No difference in frequency of hypoglycaemic attacks was found and patients claimed that IM injection was no more painful than SC injection. These data suggest that IM injection of soluble insulin into the thigh is beneficial.

Adipose Tissue↗
PubMed1990

Variation in absorption of NPH insulin due to intramuscular injection.

To evaluate the importance of accidental intramuscular injection of NPH insulin, we measured disappearance rates of 125I-labeled NPH insulin (Protaphane) from subcutaneous and intramuscular injection sites in the thighs of 11 insulin-dependent diabetes mellitus patients. Both subcutaneous and intramuscular absorption rates were measured four times in each patient. NPH insulin was absorbed much faster when given intramuscularly than when given subcutaneously (T50% = 5.3 vs. 10.3 h, P less than 0.0001). The intrapatient (day-to-day) coefficient of variation (C.V.) of T50% values (C.V. T50%) for subcutaneously injected NPH insulin in this study, where all injections were guided by ultrasound determination of the subcutaneous fat layer, was 18.4%. Intrapatient variation of absorption was significantly lower for subcutaneously than intramuscularly injected NPH insulin (C.V. T50% = 18.4 vs. 29.8%, P less than 0.01) and was also lower than interpatient variation for subcutaneously injected insulin (C.V. T50% = 18.4 vs. 50%, P less than 0.0001). The faster absorption rate and shorter duration of action, together with the higher day-to-day variation in absorption, led us to conclude that intramuscular injection of NPH insulin should be avoided.

Absorption↗
PubMed1989

NovoSol Basal: pharmacokinetics of a novel soluble long acting insulin analogue.

OBJECTIVE: To determine the courses of absorption and the interindividual and intraindividual variations in absorption of iodine-125 labelled Ultratard HM and NovoSol Basal injected subcutaneously. DESIGN: Open randomised crossover study. Each patient was tested during two study periods of five days each, during which he or she received a subcutaneous injection of either 125I-NovoSol Basal or 125I-Ultratard HM on four consecutive days. The aim was to detect a reduction in intraindividual standard deviation by a factor of two with a probability 0.95, taking 0.05 as the level of significance. This required 24 degrees of freedom and led to the choice of four courses in each of eight patients. SETTING: Referrals to the diabetes research centre in Hvidøre, Copenhagen. PATIENTS: Eight insulin dependent (type I) diabetics with low or undetectable C peptide concentrations who were receiving a multiple insulin injection regimen. One patient withdrew immediately after recruitment. INTERVENTIONS: After an overnight fast patients received 96 nmol (16 IU insulin) of either 125I-NovoSol Basal or 125I-Ultratard HM injected subcutaneously into the thigh. To ensure that the insulin entered the subcutaneous fat at the same depth, ultrasonography was performed on each patient before the first injection. A different injection site on the thigh was used each day for four days in order to facilitate monitoring of the disappearance of four different depots in each patient. MAIN OUTCOME MEASURE: Residual activity at the injection site was measured roughly every two hours throughout the day. No radioactivity measurements were performed overnight (10 pm till 8 am). The residual radioactivity after the injection on the first day (upper right thigh) was recorded for five days, that after the injection on the second day (upper left thigh) for four days, after the injection on the third day (lower right thigh) for three days, and after the last injection (lower left thigh) for two days. RESULTS: NovoSol Basal was absorbed according to first order kinetics with a mean t50% of 35.3 (SEM 1.4) hours; Ultratard HM was absorbed after a lag phase and the corresponding t50% was 25.5 (2.5) hours. The intraindividual variations in t50% were significantly smaller with NovoSol Basal than with Ultratard HM (18.4% v 44.5%; p less than 0.001). Interindividual variations, however, were not significantly different (25.2% v 36.9%; p = 0.38). The total variation in t50% was substantially smaller with NovoSol Basal than with Ultratard HM (20.3% v 42.8%). CONCLUSIONS: NovoSol Basal seems to be an appreciable advance over Ultratard HM as a soluble insulin preparation for obtaining reproducible 24 hour insulin concentrations in the blood

Absorption↗
PubMedDate not supplied

Peripheral glucose uptake and skeletal muscle GLUT4 content in man: effect of insulin and free fatty acids.

To investigate the relationship between glucose uptake and the content of the insulin regulatable glucose transporter, GLUT4, in skeletal muscle at near physiological insulin concentrations in vivo, we measured the effect of a 3h euglycemic insulin-infusion (40 mU m-2 min-1) on glucose uptake and skeletal muscle GLUT4 content in 10 healthy subjects. We found no correlation (r approximately 0.1) between individual muscle GLUT4 content and insulin-stimulated glucose uptake. Mean GLUT4 content in skeletal muscle was reduced by 19 +/- 6.3% (mean +/- SE, p less than 0.02) after insulin infusion. However, when the same subjects were made insulin resistant by infusion of lipid, as evidenced by a reduction of 16 +/- 7.2% (mean +/- SE, p less than 0.05), in insulin-stimulated glucose uptake, the effect of insulin on GLUT4 content was attenuated and no change in GLUT4 content was observed. Our results show that the total content of skeletal muscle GLUT4 is a poor predictor for in vivo response to near physiological insulin concentrations in healthy human subjects.

Adult↗