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H Beck-Nielsen

Publications and source records attributed to H Beck-Nielsen.

At least 145 records · Page 8Linked to original sources
PubMed1992

Assessment of glucose turnover rates in euglycaemic clamp studies using primed-constant [3-3H]-glucose infusion and labelled or unlabelled glucose infusates.

Underestimation of glucose turnover rates has been a problem in clamp studies using primed-constant [3-3H]-glucose infusion technique. Due to slow mixing in interstitial compartments concealed specific activity gradients may arise between plasma and interstitial compartments during intravenous unlabelled glucose infusion. Such specific activity gradients, however, can be prevented if plasma specific activity is maintained constant. Two euglycaemic clamp studies (insulin infusion 40 mU m-2 min-1) were performed in six lean normal subjects. Using conventional unlabelled glucose infusates plasma specific activity declined by 74%, tracer determined glucose appearance was smaller than actual glucose infusion rates (317 +/- 11 vs 366 +/- 15 mg m-2 min-1, p < 0.001), and erroneous negative values were calculated for glucose production (- 49 +/- 7 mg m-2 min-1). Average underestimation during the first 2 h correlated with glucose infusion rates (r = 0.88, p < 0.02). In contrast, when plasma specific activity was maintained constant, using appropriately labelled glucose infusates, tracer determined glucose appearance and glucose infusion rates were similar (385 +/- 16 vs 385 +/- 17 mg m-2 min-1), and negative errors for glucose production were avoided. In conclusion, using unlabelled glucose infusates, as in previous studies, suppression of glucose production is overestimated and stimulation of glucose utilization is underestimated. As errors were greater with larger glucose infusions, the mistakes may have been greatest in insulin sensitive control subjects, and smaller in insulin resistant subjects. Therefore, re-evaluation of hepatic insulin sensitivity seems appropriate in diabetes, obesity, and other insulin resistant states.

Adult↗
PubMed1992

Decreased insulin activation of glycogen synthase in skeletal muscles in young nonobese Caucasian first-degree relatives of patients with non-insulin-dependent diabetes mellitus.

Insulin resistance in non-insulin-dependent diabetes is associated with a defective insulin activation of the enzyme glycogen synthase in skeletal muscles. To investigate whether this may be a primary defect, we studied 20 young (25 +/- 1 yr) Caucasian first-degree relatives (children) of patients with non-insulin-dependent diabetes, and 20 matched controls without a family history of diabetes. Relatives and controls had a normal oral glucose tolerance, and were studied by means of the euglycemic hyperinsulinemic clamp technique, which included performance of indirect calorimetry and muscle biopsies. Insulin-stimulated glucose disposal was decreased in the relatives (9.2 +/- 0.6 vs 11.5 +/- 0.5 mg/kg fat-free mass per (FFM) min, P less than 0.02), and was due to a decreased rate of insulin-stimulated nonoxidative glucose metabolism (5.0 +/- 0.5 vs 7.5 +/- 0.4 mg/kg fat-free mass per min, P less than 0.001). The insulin-stimulated, fractional glycogen synthase activity (0.1/10 mmol liter glucose-6-phosphate) was decreased in the relatives (46.9 +/- 2.3 vs 56.4 +/- 3.2%, P less than 0.01), and there was a significant correlation between insulin-stimulated, fractional glycogen synthase activity and nonoxidative glucose metabolism in relatives (r = 0.76, P less than 0.001) and controls (r = 0.63, P less than 0.01). Furthermore, the insulin-stimulated increase in muscle glycogen content over basal values was lower in the relatives (13 +/- 25 vs 46 +/- 9 mmol/kg dry wt, P = 0.05). We conclude that the defect in insulin activation of muscle glycogen synthase may be a primary, possibly genetically determined, defect that contributes to the development of non-insulin-dependent diabetes.

Adult↗
PubMed1992

Effects of prolonged Acipimox treatment on glucose and lipid metabolism and on in vivo insulin sensitivity in patients with non-insulin dependent diabetes mellitus.

The effect of prolonged treatment with Acipimox on in vivo peripheral insulin sensitivity, and on glucose and lipid metabolism, was investigated in patients with NIDDM in a double-blind study. Twelve NIDDM patients were randomized to treatment with either placebo or Acipimox in pharmacological doses (250 mg x 3) for three months. Fasting plasma glucose, insulin, C-peptide and HbA1c concentrations were unaffected after three months of acipimox treatment. However, fasting plasma non-esterified fatty acid (NEFA) concentrations were twofold elevated after Acipimox treatment (1.34 +/- 0.09 vs 0.66 +/- 0.09 mmol/l; p < 0.05). Despite this, repeated acute Acipimox administration after the three months' treatment period enhanced total insulin-stimulated glucose disposal to the same extent as acute Acipimox administration before the treatment period (367 +/- 59 vs 392 +/- 66 mg.m-2.min-1, NS; both p < 0.05 vs placebo glucose disposal) (267 +/- 44 mg.m-2.min-1). In conclusion, insulin resistance or tachyphylaxis towards the effects of Acipimox on insulin stimulated glucose disposal was not induced during prolonged Acipimox treatment. The lack of improvement of blood glucose control in the patients with NIDDM may be due to the demonstrated rebound effect of lipolysis.

Diabetes Mellitus, Type 2↗
PubMed1992

Effect of acute hyperglycemia on glucose metabolism in skeletal muscles in IDDM patients.

The effect of acute hyperglycemia on glucose metabolism in skeletal muscles was assessed during replacement insulin infusion in 11 patients with insulin-dependent diabetes mellitus (IDDM). With a primed continuous [3-3H]glucose infusion and indirect calorimetry, glucose metabolism was assessed during a basal period (plasma glucose [PG] 5 mM) and during a hyperglycemic period (4-h i.v. glucose infusion, PG 12.1 mM). Biopsies were taken from the vastus lateralis muscle during both periods. On a control day, glucose metabolism was assessed in 10 patients during a basal period (PG 5.2 mM) and after 4 h with no glucose infusion (PG 4.2 mM). Nonoxidative glucose disposal increased during hyperglycemia (32 +/- 7 vs. 51 +/- 9 mg.m-2.min-1, P less than 0.05), whereas glucose oxidation remained constant. On the control day, nonoxidative glucose disposal decreased from the basal to the second (control) period (33 +/- 7 vs. 22 +/- 6 mg.m-2.min-1, P less than 0.05), and glucose oxidation remained constant. The activity of glycogen synthase in muscle biopsies (fractional velocities [0.1 and 10 mM glucose 6-phosphate (G6P)]) decreased slightly during hyperglycemia (18 +/- 2 vs. 12 +/- 2%, P less than 0.05) and on the control day (26 +/- 4 vs. 20 +/- 3%, P less than 0.05). Hyperglycemia increased the intracellular concentration of free glucose, corrected for estimated extracellular glucose (0.56 +/- 0.11 vs. 1.43 +/- 0.19 mM, P less than 0.01), G6P (0.14 +/- 0.04 vs. 0.23 +/- 0.08 mM, P less than 0.02), and lactate (2.88 +/- 0.33 vs. 4.46 +/- 0.61 mM, P less than 0.05), whereas these substrate concentrations remained constant on the control day.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1992

Insulin resistance in skeletal muscles in patients with NIDDM.

Skeletal muscles in patients with non-insulin-dependent diabetes mellitus (NIDDM) are resistant to insulin; i.e., the effect of insulin on glucose disposal is reduced compared with the effect in control subjects. This defect has been found to be localized to the nonoxidative pathway of glucose disposal; hence, the deposition of glucose, as glycogen, is abnormally low. This defect may be inherited, because it is present in first-degree relatives to NIDDM patients two to three decades before they develop frank diabetes mellitus. The cellular defects responsible for the abnormal insulin action in NIDDM patients is reviewed in this article. The paper focuses mainly on convalent insulin signaling. Insulin is postulated to stimulate glucose storage by initiating a cascade of phosphorylation and dephosphorylation events, which results in dephosphorylation and hence activation of the enzyme glycogen synthase. Glycogen synthase is the key enzyme in regulation of glycogen synthesis in the skeletal muscles of humans. This enzyme is sensitive to insulin, but in NIDDM patients it has been shown to be completely resistant to insulin stimulation when measured at euglycemia. The enzyme seems to be locked in the glucose-6-phosphate (G-6-P)-dependent inactive D-form. This hypothesis is favored by the finding of reduced activity of the glycogen synthase phosphatase and increased activity of the respective kinase cAMP-dependent protein kinase. A reduced glycogen synthase activity has also been found in normoglycemic first-degree relatives of NIDDM patients, indicating that this abnormality precedes development of hyperglycemia in subjects prone to develop NIDDM. Therefore, this defect may be of primary genetic origin. However, it does not appear to be a defect in the enzyme itself, but rather a defect in the covalent activation of the enzyme system. Glycogen synthase is resistant to insulin but may be activated allosterically by G-6-P. This means that the defect in insulin activation can be compensated for by increased intracellular concentrations of G-6-P. In fact, we found that both hyperinsulinemia and hyperglycemia are able to increase the G-6-P level in skeletal muscles. Thus, insulin resistance in the nonoxidative pathway of glucose processing can be overcomed (compensated) by hyperinsulinemia and hyperglycemia. In conclusion, we hypothesize that insulin resistance in skeletal muscles may be a primary genetic defect preceding the diabetic state. The cellular abnormality responsible for that may be a reduced covalent insulin activation of the enzyme glycogen synthase.(ABSTRACT TRUNCATED AT 400 WORDS)

Diabetes Mellitus, Type 2↗
PubMed1992

[Insulin treatment--its physiological principle].

Insulin treatment based on the physiological principle not only results in better glucose homeostasis but also in improved quality of life for the patients. The frequency of metabolic events also seems to be controlled, particularly when the multiple injection system is used. However, a prerequisite is regular, preferably daily, blood sugar monitoring to enable the insulin dosage to be adapted according to food intake and exercise. Advances in our knowledge of the importance of the injection technique used may contribute to the optimisation of insulin treatment and thus of glucose homeostasis.

Absorption↗
PubMed1991

[Magnesium deficiency and development of late diabetic complications].

Diabetics have a higher prevalence of recurrent angina, myocardial infarction and hypertension compared with healthy individuals. This is partly due to the metabolic control, and partly to the development of nephropathy, but inherited factors also seem to contribute to their development. Another factor, to some extent inherited, could be magnesium-deficiency. Up to 30% of all diabetics suffer from magnesiumdepletion, which in other disease entities has been related to angina pectoris, myocardial infarction, and changes in blood lipids. Furthermore, magnesium-deficiency might be related to the development of hypertension. In diabetes, magnesium-depletion has been linked with the development of retinopathy, and an increase in abortions and malformations in diabetic pregnancies. No intervention trials with magnesium, to elucidate the question of magnesium depletion and diabetic late complications have hitherto been made. No methods for assessing magnesium-status in diabetes are available as yet, to select patients for this type of trial.

Diabetes Mellitus, Type 1↗
PubMed1991

Effects of sulfonylureas on adipocyte and skeletal muscle insulin action in patients with non-insulin-dependent diabetes mellitus.

The effect of glibenclamide treatment on insulin action in isolated fat cells was studied in eight moderately obese patients with non-insulin-dependent diabetes mellitus (NIDDM). Insulin receptor binding and the effect of insulin on glucose transport and lipogenesis were determined before and after 3 months of glibenclamide therapy. At the end of the treatment period, mean daytime plasma glucose concentrations were reduced (10.8 +/- 0.4 versus 7.0 +/- 0.3 mmol/L, p less than 0.001) whereas mean daytime plasma insulin level was increased (40 +/- 12 versus 71 +/- 9 mU/L, p less than 0.001). Adipocyte insulin receptor binding as well as basal glucose transport and metabolism were unaffected by drug treatment. In contrast, insulin-stimulated glucose transport and lipogenesis were both significantly enhanced (p less than 0.05). These findings are comparable to those of another study involving seven moderately obese subjects with NIDDM who had biopsies of the lateral vastus muscle taken for measurement of insulin receptor function and glycogen synthase activity before and during 2 months of gliclazide treatment. In that study insulin receptors purified with wheatgerm agglutinin showed unchanged insulin binding and receptor kinase activity. Moreover, gliclazide had no impact on maximal glycogen synthase activity. However, under physiologic hyperinsulinemic conditions gliclazide therapy was associated with an increased sensitivity of glycogen synthase for its allosteric activation by glucose-6-phosphatase (p less than 0.04). In conclusion, sulfonylurea treatment of NIDDM enhances insulin-stimulated peripheral glucose utilization in part through a potentiation of insulin action on adipose tissue glucose transport and lipogenesis and skeletal muscle glycogen synthase.

Adipose Tissue↗
PubMed1991

Reduced glycogen synthase activity in skeletal muscle from obese patients with and without type 2 (non-insulin-dependent) diabetes mellitus.

In order to evaluate the importance of a defect in insulin mediated non-oxidative glucose metabolism and glycogen synthase activity in skeletal muscles in obese subjects with and without Type 2 (non-insulin-dependent) diabetes mellitus we studied: 10 lean and 10 obese control subjects and 12 obese diabetic patients using the euglycaemic hyperinsulinaemic clamp technique (basal, 20 mU.(m2)-1.min-1, 80 mU.(m2)-1.min-1) in combination with indirect calorimetry. Muscle biopsies were taken from m. vastus lateralis at each insulin level. We found that non-oxidative glucose metabolism could be stimulated by insulin in all three groups (p less than 0.01). The values obtained at the highest insulin levels (around 140 microU/ml) were lower in both obese groups compared to the lean control subjects (118 +/- 21, 185 +/- 31, 249 +/- 14 mg.(m2)-1.min-1 (p less than 0.01]. Insulin stimulation of the glycogen synthase activity at a glucose-6-phosphate concentration of 0.1 mmol/l was absent in both obese groups, while activities increased significantly in the lean control subjects (19.6 +/- 4.2% to 45.6 +/- 6.8%, p less than 0.01). Glycogen synthase activities at the highest insulin concentrations only differed significantly between lean control subjects and obese diabetic patients (45 +/- 7% and 31 +/- 5%, p less than 0.05). We conclude that insulin resistance in peripheral tissues in obese subjects with and without Type 2 diabetes may be partly explained by a reduced insulin mediated non-oxidative glucose metabolism and that this abnormality might be due to an absent insulin stimulation of glycogen synthase in skeletal muscles. This enzyme defect is correlated to obesity itself.

Allosteric Regulation↗
PubMed1991

Effect of insulin on renal sodium handling in hyperinsulinaemic type 2 (non-insulin-dependent) diabetic patients with peripheral insulin resistance.

The sodium retaining effect of insulin was studied in ten Type 2 (non-insulin-dependent) diabetic patients (mean age 56 (43-73) years, mean body mass index 29.5 (24.2-33.7) kg/m2) and eight age-matched control subjects (mean age 57 (43-68) years, mean body mass index 23.4 (20.8-26.6) kg/m2). The renal clearances of 99mTc-DTPA, lithium, sodium and potassium were measured over a basal period of 90 min. Then insulin was infused at a rate of 40 mU.min-1.m-2. After an equilibration period of 90 min, the clearance measurements were repeated during a new 90 min period. Blood glucose was clamped at the basal level (diabetic patients: 9.9 +/- 3.5, control subjects: 5.3 +/- 0.5 mmol/l) by a variable glucose infusion. Basal plasma insulin concentration was elevated in the diabetic patients (0.12 +/- 0.05 vs 0.05 +/- 0.02 pmol/ml, p less than 0.01). Insulin infusion resulted in comparable absolute increments in plasma insulin concentrations in the diabetic group and in the control group (0.44 +/- 0.13 vs 0.36 +/- 0.07 pmol/ml, NS). The metabolic clearance rate of glucose during the last 30 min of insulin infusion was lower in the diabetic patients (155 +/- 62 vs 320 +/- 69 ml.min-1.m-2, p less than 0.01), reflecting peripheral insulin resistance. The decline in sodium clearance during insulin infusion was similar in diabetic subjects (1.8 +/- 1.1 vs 0.7 +/- 0.4 ml.min-1.1.73 m-2, p less than 0.01) and in control subjects (1.7 +/- 0.3 vs 0.8 +/- 0.3 ml.min-1.1.73 m-2, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1991

Concentration-response relationship in paroxetine treatment of diabetic neuropathy symptoms: a patient-blinded dose-escalation study.

A single-blind dose-escalation study with the selective serotonin reuptake inhibitor paroxetine was conducted in 19 diabetic patients with neuropathy symptoms. The effect of treatment was evaluated by self-rating using visual analog scales. After an initial placebo period, paroxetine doses were increased from 10 mg/day in 10 mg steps, until the dose was 30-70 mg/day. In all except four patients, there was a marked relief of symptoms. Plasma concentrations of paroxetine above 300-400 nM were required to insure maximal relief in the majority of patients responding on paroxetine, but a considerable interindividual variation was observed (10-800 nM, median of 195 nM). The therapeutic effect appeared to increase gradually as the plasma concentration increased. The great interindividual variation in the pharmacokinetics of paroxetine was confirmed, but as the effect is maximal within approximately 1 week, and the drug is nontoxic, it may be clinically feasible simply to titrate the dose from 20 mg/day until the maximal effect is achieved. However, it is advised that titration to an effect, in diabetic neuropathy using doses above 50 mg/day, be undertaken with care as there is limited experience with doses above this level in any population. The beneficial effect of paroxetine appeared to be maintained unaltered during an additional 1 month open-label treatment on optimal paroxetine doses.

Adult↗
PubMed1991

Absorption of NPH (isophane) insulin in resting diabetic patients: evidence for subcutaneous injection in the thigh as the preferred site.

The absorption kinetics of NPH (isophane) insulin injected subcutaneously into the abdominal wall and subcutaneously (SC) and intramuscularly (IM) into the thigh was studied in 11 Type 1 diabetic patients. The thickness of the subcutaneous adipose tissue layer was measured by ultrasound. NPH (isophane) insulin injected IM into the thigh was absorbed faster than NPH insulin injected SC into the thigh (T50%, IM 8.0 +/- 0.6 h and SC 10.3 +/- 0.7 h, p less than 0.05). No difference in T50% values was found for injection into the abdominal wall (9.7 +/- 1.2h) compared with the thigh. The mean absorption rate from 1.5 to 13.5 h after injection was higher after injection IM into the thigh (6.4 +/- 0.3% of initial dose injected absorbed per h) than after SC injection into the thigh (5.2 +/- 0.3% h-1) and SC into the abdominal wall (5.1 +/- 0.3% h-1) (p less than 0.01). The most constant absorption rate was obtained after SC injection into the thigh (within-study day CV of the mean absorption rate 19.9 +/- 3.2% vs 34.4 +/- 3.2% after IM injection into the thigh and 27.1 +/- 4.9% after SC injection into the abdominal wall (p less than 0.02]. The study provides further evidence that the subcutaneous tissue of the thigh is the preferred injection site for NPH insulin.

Absorption↗
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

Insulin resistance, but normal basal rates of glucose production in patients with newly diagnosed mild diabetes mellitus.

Fasting hyperglycemia in Type II (non-insulin-dependent) diabetes has been suggested to be due to hepatic overproduction of glucose and reduced glucose clearance. We studied 22 patients (10 lean and 12 obese) with newly diagnosed mild diabetes mellitus (fasting plasma glucose less than 15 mmol/l, urine ketone bodies less than 1 mmol/l), and two age- and weight-matched groups of non-diabetic control subjects. Glucose turnover rates and sensitivity to insulin were determined using adjusted primed-continuous [3-3H]glucose infusion and the hyperinsulinemic euglycemic clamp technique. Insulin-stimulated glucose utilization was reduced in both diabetic groups (lean patients: 313 +/- 35 vs 531 +/- 22 mg.m-2.min-1, p less than 0.01; obese patients: 311 +/- 28 vs 453 +/- 26 mg.m-2.min-1, p less than 0.01). Basal plasma glucose concentrations decreased 0.43 +/- 0.05 mmol/l per h (p less than 0.01). Glucose production rates were smaller than glucose utilization rates (lean patients: 87 +/- 3 vs 94 +/- 3 mg.m-2.min-1, p less than 0.01; obese patients: 79 +/- 5 vs 88 +/- 5 mg.m-2.min-1, p less than 0.01), were not correlated to basal glucose or insulin concentrations, and were not different from normal (lean controls: 87 +/- 4 mg.m-2.min-1; obese controls: 80 +/- 5 mg.m-2.min-1). These results suggest that the basal state in the diabetic patients is a compensated condition where glucose turnover rates are maintained near normal despite defects in insulin sensitivity.

Adult↗
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↗
PubMed1991

Basal glucose metabolism in type 2 diabetes. A critical review.

In the current review we have re-evaluated the concept of markedly elevated basal glucose production rates in patients with Type 2 diabetes. Owing to underpriming of the enlarged glucose pool in hyperglycaemic Type 2 diabetic patients most previous studies using the primed-continuous tracer infusion technique may have markedly overestimated basal glucose production rates in proportion to the level of hyperglycaemia. Also previous studies using an adequate priming ratio may have overestimated glucose production to some extent due to assumptions of steady state conditions. Using adjusted priming and non-steady state calculations we have found near normal rates of basal glucose production and glucose utilization in obese patients with Type 2 diabetes. The presence of insulin resistance in these patients was confirmed using the euglycaemic clamp technique. Thus, it is suggested that the basal state in Type 2 diabetes may be considered as a compensated condition where glucose turnover rates are maintained near normal. Hyperinsulinaemia and hyperglycaemia may serve as compensating factors, compensating for the defects in insulin action.

Blood Glucose↗
PubMed1990

Kinetics of insulin binding and kinase activity of the partially purified insulin receptor from human skeletal muscle.

The kinetics of insulin binding and kinase activity of soluble, partially purified insulin receptors from human skeletal muscle are considered. An equilibrium for insulin binding was obtained within 2 h at 37 degrees C. At lower temperatures the equilibrium for insulin binding was less clearly defined. Dissociation of 125I-labelled insulin was incomplete unless an excess amount of unlabelled insulin was added. Insulin-stimulatable autophosphorylation of the 95 kDa subunit was verified by gel electrophoresis. The kinase activity was measured with the synthetic polypeptide poly(Glu-Tyr(4:1] as a phosphoacceptor. The insulin receptor kinase activity correlated significantly (r = 0.92, P less than 0.0001) to the concentration of high-affinity insulin binding sites in the eluate. Autophosphorylation of the insulin receptor was necessary for the activation of the receptor kinase. When activated the receptor kinase activity was stable for at least 60 min at 21 degrees C with a pH optimum of approx. 7.8, similar to the pH optimum for insulin binding. The non-ionic detergent Triton X-100 inhibited the sensitivity of the receptor kinase to insulin. Insulin stimulated the Vmax of the kinase reaction about 3-fold, decreased the Km for ATP from 35 +/- 5 microM (mean +/- S.E.) to 8 +/- 1 microM (P less than 0.02) and induced a positive cooperativity to ATP with an increase in the Hill coefficient from 1.00 +/- 0.02 to 1.37 +/- 0.07 (P less than 0.05). According to the Hill plots, insulin itself showed no cooperativity with respect to receptor binding or kinase activation.

Adenosine Triphosphate↗