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Hyperinsulinaemic Clamp Technique (hyperinsulinaemic + clamp_technique)

Distribution by Scientific Domains
Medical Sciences85%

Kinds of Hyperinsulinaemic Clamp Technique

  • euglycaemic hyperinsulinaemic clamp technique
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    Selected Abstracts

    Equine laminitis: Ultrastructural lesions detected in ponies following hyperinsulinaemia

    EQUINE VETERINARY JOURNAL, Issue 7 2009
    A. R. NOURIAN
    Summary Reasons for performing study: Anatomical changes in the hoof lamellar tissue induced by prolonged hyperinsulinaemia have not been described previously. Analysis of the induced lesions may promote understanding of hyperinsulinaemic laminitis pathogenesis and produce clinical benefit. Objectives: To use light and transmission electron microscopy (TEM) to document hoof lamellar lesions in ponies clinically lame after prolonged hyperinsulinaemia. Methods: Nine clinically normal, mature ponies were allocated randomly to either a treatment group (n = 5) or control group (n = 4). The treatment group received insulin via a modified, prolonged euglycaemic hyperinsulinaemic clamp technique (EHCT) and were subjected to euthanasia when clinical signs of Obel grade II laminitis occurred. The control group was sham treated with an equivalent volume of 0.9% saline and killed at 72 h. Lamellar tissues of the right front feet were harvested and processed for TEM. Results: Lamellae from insulin treated ponies were attenuated and elongated with many epidermal basal cells (EBC) in mitosis. Unlike carbohydrate induced laminitis in horses there was no global separation at the lamellar dermal/epidermal interface among ponies. Sporadic EBC basement membrane (BM) separation was associated with the proximity of infiltrating leucocytes. In 2 ponies, the lamellar BM was thickened. The number of hemidesmosomes/,m of BM was decreased in all insulin treated ponies. Conclusions: Prolonged hyperinsulinaemia causes unique lamellar lesions normally characteristic of acute and chronic laminitis. Lamellar proliferation may be an insulin effect through its mitogenic pathway. Aberrant lamellar mitosis may lengthen and weaken the lamellar, distal phalanx attachment apparatus and contribute to the clinical signs that developed. Potential relevance: The study shows that insulin alone, in higher than normal circulating concentrations, induces profound, changes in lamellar anatomy. Medical control of insulin resistance and hyperinsulinaemia may ameliorate lesions and produce clinical benefit. [source]

    The effect of long-term exercise on glucose metabolism and peripheral insulin sensitivity in Standardbred horses

    EQUINE VETERINARY JOURNAL, Issue S36 2006
    E. de GRAAF-ROELFSEMA
    Summary Reasons for performing study: To study the possible long-term effect of improved glucose tolerance in horses after long-term training, as the impact of exercise training on glucose metabolism is still unclear in the equine species. It is not known whether there is a direct long-term effect of training or if the measurable effect on glucose metabolism is the residual effect of the last exercise session. Objectives: To determine the chronic effect on glucose metabolism and peripheral insulin sensitivity of long-term training in horses by use of the euglycaemic hyperinsulinaemic clamp technique. Methods: Eleven Standardbred horses were acclimatised to running on the high-speed treadmill for 4 weeks (Phase 1) followed by training for 18 weeks with an alternating endurance (, 60% HRmax) high intensity training programme (, 80% HRmax) (Phase 2). Training frequency was 4 days/week. At the end of Phase 1, a euglycaemic hyperinsulinaemic clamp was performed 72 h after the last bout of exercise in all horses. At the end of Phase 2, the horses were clamped 24 h or 72 h after the last bout of exercise. Results: Glucose metabolism rate did not change significantly after 18 weeks of training, measured 72 h after the last exercise bout (0.018 ± 0.009 and 0.022 ± 0.006 mmol/kg bwt/min, respectively). Peripheral insulin sensitivity also did not change significantly following training (7.6 ± 5.7 times 10,6 and 8.0 ± 3.1 times 10,6, respectively). The same measurements 24 h after the last bout of exercise showed no significant differences. Conclusions: Results indicated that long-term training in Standardbreds neither changed glucose metabolism or insulin sensitivity 72 h after the last bout of exercise. Potential relevance: The fact that the beneficial effect of increased insulin sensitivity after acute exercise diminishes quickly in horses and no long-term effects on insulin sensitivity after chronic exercise have as yet been found in horses, implies that exercise should be performed on a regular basis in horses to retain the beneficial effect of improved insulin sensitivity. [source]

    Gender-dependent effect of ageing on peripheral insulin action

    INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 4 2005
    A-M. Borissova
    Summary The aim of the present study was to investigate the effect of both gender and age on insulin secretion, peripheral insulin effectiveness and insulin-receptor binding. Eighty healthy volunteers, 40 females of mean age 38.47 ± 11.37 years and mean BMI 21.99 ± 2.06 kg/m2 and 40 males of mean age 34.87 ± 11.22 years and mean BMI 22.65 ± 2.31 kg/m2, with normal glucose tolerance participated in the study. Peripheral insulin effectiveness was measured by the artificial endocrine pancreas, using the euglycaemic hyperinsulinaemic clamp technique and insulin-receptor binding on circulating mononuclear blood cells. Peripheral insulin sensitivity was significantly higher in females as compared to males (p < 0.001), while males demonstrated higher total number of insulin receptors (p < 0.0001) and number of high-affinity receptors (p < 0.01). Peripheral insulin sensitivity decreased with ageing in both males and females, the reduction in females being more pronounced (p < 0.05). In the group under 40 years, the females demonstrated significantly higher insulin sensitivity as compared to males (p < 0.001) and lower insulin-receptor binding. Over 40 years, females presented higher peripheral insulin sensitivity and higher insulin-receptor binding. The percentage of specifically bound insulin increased significantly with ageing in females and decreased in males. We consider that probably the higher androgen level in males affects the post-receptor processes in insulin action and despite the higher insulin-receptor binding, males have lower insulin sensitivity. The androgen levels in females increase with ageing, which could probably affect peripheral insulin sensitivity at the post-receptor level. In conclusion, our results demonstrate that when analysing peripheral insulin effectiveness and insulin-receptor binding, one should always consider both gender and age. [source]

    An insulin-resistant hypertriglyceridaemic normotensive obese dog model: assessment of insulin resistance by the euglycaemic hyperinsulinaemic clamp in combination with the stable isotope technique

    JOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 3-4 2003
    E. Bailhache
    Summary Many studies have shown that in humans insulin resistance (IR) is associated with obesity and hypertriglyceridaemia. The aim of our study was to develop slowly dietary-induced obesity in dogs through long-term overfeeding of a high-fat diet, and to characterize this IR, hypertriglyceridaemic and normotensive model. Insulin resistance was assessed by the euglycaemic hyperinsulinaemic clamp technique. The contribution of hepatic glucose production during the clamp was evaluated using a constant stable-isotope-labelled glucose infusion. Overfeeding a high-fat diet for 7 months was associated with a 43 ± 5% body weight increase. Insulin resistance was characterized by hyperinsulinaemia in the unfed state (10 ± 1 vs. 24 ± 1 ,U/ml, in healthy and obese dogs, respectively, p < 0.02) and by a reduction of the insulin-mediated glucose uptake (28 ± 3 vs. 16 ± 1 mg/kg/min, p < 0.02). Hepatic glucose production suppression under insulin infusion allowed to conclude that this reduced glucose uptake resulted from a decrease of insulin sensitivity in obese dogs. Furthermore, animals remained normotensive and exhibited a marked hypertriglyceridaemia (0.26 ± 0.04 vs. 0.76 ± 0.15 mmol/l, in healthy and obese dogs, respectively, p < 0.02). Because hypertriglyceridaemia is the most common lipid abnormality in insulin-resistant humans, this dog with slowly induced obesity may constitute a good model to study the consequences of IR in lipid metabolism independently of vascular changes. [source]

    Liver fat and lipid oxidation in humans

    LIVER INTERNATIONAL, Issue 9 2009
    Anna Kotronen
    Abstract Background: Studies in animals show that changes in hepatic fatty acid oxidation alter liver fat content. Human data regarding whole-body and hepatic lipid oxidation are controversial and based on studies of only a few subjects. Aims: We examined whether whole-body and hepatic lipid oxidation are altered in subjects with non-alcoholic fatty liver disease (NAFLD) compared with controls. Methods: In vivo measurements of rates of substrate oxidation and insulin sensitivity (using the euglycaemic hyperinsulinaemic clamp technique in combination with indirect calorimetry and infusion of [3- 3H]glucose) were performed in subjects with NAFLD [mean liver fat 14.0% (interquartile range 7.5,20.5%), n=29] and in control subjects [1.6% (1.0,3.0%), n=29]. Liver fat was measured using proton magnetic resonance spectroscopy. Plasma concentrations of 3-hydroxybutyrate (3-OHB) were measured as markers of hepatic lipid oxidation. Results: In the basal state, substrate oxidation rates and serum 3-OHB concentrations were comparable in subjects with and without NAFLD. Plasma 3-OHB concentrations were similarly suppressed by insulin in both the groups. During the insulin infusion, whole-body lipid oxidation was inversely correlated with insulin-stimulated glucose disposal (r=,0.48, P<0.0001), which was lower in subjects with NAFLD [3.7±0.2 mg/(kg fat-free mass min)] than in the control subjects [5.0±0.3 mg/(kg fat-free mass min), P=0.0008]. Conclusions: Hepatic lipid oxidation is unchanged in NAFLD. Whole-body lipid oxidation is increased because of peripheral insulin resistance. These data imply that alterations in hepatic fatty acid oxidation do not contribute to liver fat content in humans. [source]

    Measuring the acute effect of insulin infusion on ATP turnover rate in human skeletal muscle using phosphorus-31 magnetic resonance saturation transfer spectroscopy

    NMR IN BIOMEDICINE, Issue 8 2010
    Ee Lin Lim
    Abstract Mitochondrial dysfunction has been proposed to underlie the insulin resistance of type 2 diabetes. However, the relative time course of insulin action in stimulating ATP turnover rate and glucose uptake in skeletal muscle has not been examined. These two parameters were measured in young healthy subjects using the 31P MRS saturation transfer method in conjunction with the euglycaemic hyperinsulinaemic clamp technique respectively. Glucose infusion rate rose rapidly from 0 to 2.90,±,0.11,mg/kgffm/min during the first 10,min of insulin infusion and further to 6.17,±,0.57,mg/kgffm/min between 15 and 45,min. In contrast, baseline ATP turnover rate was 9.0,±,0.4,µmol/g/min of muscle and did not change during the first 45,min of insulin infusion. Between 50 and 80,minutes ATP turnover rate increased by 8% and remained steady to 150,minutes (9.7,±,0.5 µmol/g/min of muscle, p,=,0.03 vs baseline). The in vivo time course of insulin stimulation of skeletal muscle ATP turnover rate is not consistent with a rate limiting effect upon the initiation of insulin-stimulated glycogen synthesis. Copyright © 2010 John Wiley & Sons, Ltd. [source]

    Effects of T4 replacement therapy on glucose metabolism in subjects with subclinical (SH) and overt hypothyroidism (OH)

    CLINICAL ENDOCRINOLOGY, Issue 6 2008
    Ammon Handisurya
    Summary Objective To evaluate ,-cell function and insulin sensitivity in subjects with overt (OH) and subclinical hypothyroidism (SH) before and after T4 replacement therapy. Background Disturbances in glucose metabolism have been observed in hypothyroid states. However, the clinical significance and potential reversibility of these alterations by T4 replacement therapy remain to be elucidated especially in patients with SH. Design and patients Parameters of glucose metabolism have been investigated in subjects with OH (n = 12) and SH (n = 11). Insulin sensitivity has been assessed by the euglycaemic,hyperinsulinaemic clamp technique and ,-cell function by mathematical modelling of data derived from an oral glucose tolerance test. Results Fasting and dynamic glycaemia as assessed by the AUCGlucose remained unaltered following substitution therapy (P > 0·05). Insulin sensitivity significantly improved only in subjects with OH (P < 0·05). Fasting insulin and proinsulin concentrations increased proportionally in both groups (P < 0·05) with the proinsulin : insulin ratio remaining unchanged (P > 0·05). Total insulin secretion was higher in OH before initiation of therapy (P < 0·05). In both groups, dynamic parameters including total insulin secretion, hepatic insulin extraction and the adaptation index were significantly attenuated (P < 0·05) after restoration of thyroid function, whereas the disposition index and the basal insulin secretion rate remained unaltered (P > 0·05). Conclusion In summary, SH and OH are characterized by attenuated basal plasma insulin levels and increased glucose-induced insulin secretion. T4 replacement therapy partially ameliorates the insulin secretion profile and reduces the demand on pancreatic ,-cells after glucose challenge to an extent that exceeds any effect attributable to the improvement in insulin sensitivity. [source]