Home About us Contact
|
Home About us Contact | ||
|
|
||
Glucose Infusion Rate (glucose + infusion_rate)
Selected AbstractsMeasuring the acute effect of insulin infusion on ATP turnover rate in human skeletal muscle using phosphorus-31 magnetic resonance saturation transfer spectroscopyNMR IN BIOMEDICINE, Issue 8 2010Ee 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] The glucose lowering effect of an oral insulin (Capsulin) during an isoglycaemic clamp study in persons with type 2 diabetesDIABETES OBESITY & METABOLISM, Issue 1 2010S. D. Luzio Aim: Randomized, open, single-centre, two-way crossover study comparing the pharmacokinetic (PK) and pharmacodynamic (PD) properties of subcutaneous (sc) regular human insulin (Actrapid) and oral insulin in a capsule form (Capsulin). Methods: Sixteen persons (12 males) with type 2 diabetes on oral hypoglycaemic agents (OHAs) participated. Mean (s.d.) age 60.2 (5.5) years, BMI 28.3 (3.4) kg/m2, haemoglobin A1c (HbA1c) 7.4% (1.1). Two 6-h isoglycaemic glucose clamp studies were conducted 11 days apart. All subjects received in random order 12U sc Actrapid on one clamp study day and either 150U or 300U Capsulin (Cap) on the other day. Glucose infusion rates (GIRs), plasma insulin and C-peptide concentrations were determined throughout each 6-h isoglycaemic clamp. Between the clamp study days, all patients received 150U Capsulin twice daily, dropping all their standard OHAs apart from metformin. Self-monitored blood glucose (SMBG) levels were taken four times a day between the clamp study days. Results: Administration of either Actrapid or Capsulin (150 and 300U) increased GIRs reaching a maximum values at approximately 280,330 min. Overall values for maximum GIR values were higher for Actrapid than either dose of Capsulin (p < 0.05). The significantly greater systemic insulin concentrations following Actrapid were reflected in the AUC0,6 h (910 ± 270 vs. 472 ± 245 pmol h/L; 950 ± 446 vs. 433 ± 218 pmol h/L; both p < 0.05 for Actrapid vs. 150U Capsulin and 300U Capsulin respectively). No difference was observed between 150U and 300U Capsulin. During the repeat-dosing period, good safety and tolerability were observed with Capsulin, and SMBG levels remained stable. At the poststudy visit, significant falls in HbA1c, weight and triglycerides were observed. Conclusions: Administration of the oral insulin Capsulin preparation demonstrated a significant hypoglycaemic action over a period of 6 h associated with only a small increase in circulating plasma insulin concentrations. [source] Is postprandial hypertriglyceridaemia in relatives of type 2 diabetic subjects a consequence of insulin resistance?EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2005A. Kriketos Abstract Background, Higher postprandial triglyceride responses reported in first degree relatives of people with type 2 diabetes (REL) were postulated to be the result of an early, possibly intrinsic, defect in oral lipid handling. The postprandial triglyceride response to high fat meals (HFM) in normal subjects is reduced by the insulin response to dietary carbohydrate (CHO) in the meal. The aims of this study were to examine whether (1) insulin resistance is associated with an intrinsic defect in triglyceride handling in insulin-resistant REL and (2) insulin resistance is associated with altered triglyceride handling after HFM with high CHO content. Materials and methods, Postprandial responses to a HFM in normolipidaemic, normoglycaemic REL were compared with subjects without a family history of diabetes mellitus (CON). Over 6 h, the insulin, glucose, triglyceride and nonesterified fatty acid (NEFA) responses after a high fat (80 g fat), low CHO (HFM-LC; 20 g CHO, 4250 kJ) meal and a high fat, high CHO (HFM-HC; 100 g CHO, 5450 kJ) meal were examined. Results, The 10 (7F/3M) REL were significantly more insulin-resistant, determined by glucose infusion during a hyperinsulinaemic euglycaemic clamp than the 10 (5F/5M) CON (glucose infusion rate 44·6 ± 4·9 vs. 60·0 ± 4·8 µmol min,1 kg FFM,1, P = 0·037). Subjects were similar for age and body mass index (BMI). The triglyceride increments after the HFM-LC were similar in both, peaking at 180,240 min (,0·77 ± 0·11 mmol L,1), demonstrating no postprandial defect in REL, despite insulin resistance. There was a significantly lower postprandial triglyceride response in CON following the HFM-HC compared with the HFM-LC, but not in REL. In contrast, the higher insulin level during the HFM-HC was associated with significantly greater NEFA level suppression than in the HFM-LC (2·13 ± 0·51 vs. 0·70 ± 0·35 mmol L,1, P = 0·03), only in the REL. Conclusions, These results are inconsistent with a primary aetiological role for postprandial hypertriglyceridaemia in already insulin resistant type 2 diabetic REL, but raise the possibility that this potentially atherogenic manifestation is secondary to insulin resistance lessening VLDL production and/or release from the liver. [source] Effects of dietary protein level and cold exposure on tissue responsiveness and sensitivity to insulin in sheepJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 11-12 2001H. Sano The effects of dietary crude protein (CP) level and cold exposure on tissue responsiveness and sensitivity to insulin were studied in sheep. Nine rams were assigned to one of three isoenergetic diets which contained 70, 100, and 140% of CP for maintenance. They were exposed from a thermoneutral environment (20 °C) to a cold environment (0 °C) for 7 days. A hyperinsulinemic euglycemic clamp approach was applied for the determination of tissue responsiveness to insulin (the maximal glucose infusion rate, GIRmax) and tissue sensitivity to insulin (the plasma insulin concentration at half maximal glucose infusion rate, ED50). Dietary CP level influenced digestibilities of dry matter and CP (P=0.002 and P=0.001, respectively), and cold exposure decreased (P=0.01) CP digestibility. The GIRmax and ED50 tended to be influenced (P=0.08) by dietary CP level. The GIRmax was enhanced (P=0.0001) during cold exposure. Significant interactions between diet and environment were found for the GIRmax (P=0.04), but not for ED50 (P=0.07). It is concluded that in sheep dietary CP level can modify insulin action in response to cold exposure. [source] Intermuscular adipose tissue (IMAT): Association with other adipose tissue compartments and insulin sensitivityJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 6 2009Michael Boettcher MD Abstract Purpose To quantify intermuscular adipose tissue (IMAT) of the lower leg as well as to investigate associations with other adipose tissue (AT) compartments. The relationship between IMAT and insulin sensitivity was also examined. Materials and Methods Standardized quantification of IMAT was performed in a large cohort (N = 249) at increased risk for type 2 diabetes in the right calf by T1-weighted fast spin-echo imaging at 1.5T (Magnetom Sonata; Siemens Healthcare). Additionally, whole-body AT distribution was assessed. Insulin sensitivity was determined by glucose clamp. Results Males showed significantly more IMAT than females (2.1 ± 1.1 cm2 vs. 1.5 ± 0.9 cm2; P < 0.001). IMAT correlated well with other AT depots, especially with visceral AT (VAT; rfemales = 0.52, P < 0.0001 vs. rmales = 0.42, P < 0.0001). Moreover, IMAT showed a negative correlation with the glucose infusion rate (GIR; rfemales = ,0.43, P = 0.0002 vs. rmales = ,0.40, P = 0.0007). Conclusion Quantification of IMAT is possible by standard MR techniques. AT distribution of the lower leg is comparable to the visceral compartment with males having higher IMAT/VAT but lower subcutaneous AT (SCAT). IMAT seems to be involved in the pathogenesis of insulin resistance, as shown by the significant negative correlation with GIR. J. Magn. Reson. Imaging 2009. © 2009 Wiley-Liss, Inc. [source] Standardized protocol for a depletion of intramyocellular lipids (IMCL)NMR IN BIOMEDICINE, Issue 5 2010Michael Ith Abstract Intramyocellular lipids (IMCL) are flexible fuel stores that are depleted by physical exercise and replenished by fat intake. IMCL or their degradation products are thought to interfere with insulin signaling thereby contributing to insulin resistance. From a practical point of view it is desirable to deplete IMCL prior to replenishing them. So far, it is not clear for how long and at which intensity subjects have to exercise in order to deplete IMCL. We therefore aimed at developing a standardized exercise protocol that is applicable to subjects over a broad range of exercise capacity and insulin sensitivity and allows measuring reliably reduced IMCL levels. Twelve male subjects, including four diabetes type 2 patients, with wide ranges of exercise capacity (VO2peak per total body weight 27.9,55.8,ml*kg,1*min,1), insulin sensitivity (glucose infusion rate per lean body mass 4.7,15.3,mg*min,1*kg,1), and BMI (21.7,31.5,kg*m,2), respectively, were enrolled. Using 1H magnetic resonance spectroscopy (1H-MRS), IMCL was measured in m.tibialis anterior and m.vastus intermedius before and during a depletion protocol of a week, consisting of a moderate additional physical activity (1,h daily at 60% VO2peak) and modest low-fat (10,15%) diet. Absolute IMCL-levels were significantly reduced in both muscles during the first 3 days and stayed constant for the next 3 days of an identical diet/exercise-scheme. These reduced IMCL levels were independent of insulin sensitivity, yet a tendency to lower depleted IMCL levels has been observed in subjects with higher VO2peak. The proposed protocol is feasible in subjects with large differences in exercise capacity, insulin sensitivity, and BMI, leading to reduced IMCL levels that neither depend on the exact duration of the depletion protocol nor on insulin sensitivity. This allows for a standardized preparation of IMCL levels either for correlation with other physiological parameters or for replenishment studies. Copyright © 2010 John Wiley & Sons, Ltd. [source] Successful treatment of severe subcutaneous insulin resistance with inhaled insulin therapyPEDIATRIC DIABETES, Issue 6 2010AAEM Van Alfen-van der Velden van Alfen-van der Velden AAEM, Noordam C, de Galan BE, Hoorweg-Nijman JJG, Voorhoeve PG, Westerlaken C. Successful treatment of severe subcutaneous insulin resistance with inhaled insulin therapy. The potential of inhaled insulin therapy for severe resistance to subcutaneous insulin was tested in a 7-yr old boy with type 1 diabetes mellitus. The efficiency of 1 mg inhaled insulin (Exubera®) was examined by a 4-h euglycemic clamp study. During the clamp, the glucose infusion rate started to increase 25 min after inhalation and peaked 120 min after inhalation. Subsequently, a trial of inhaled insulin monotherapy was initiated consisting of pre-meal inhalations and one inhalation during the night. Since glycemic control remained fair (HbA1c ,8.5%), this therapy was continued. Over the ensuing 18 months, mild keto-acidosis occurred twice during gastro-enteritis. Inhaled insulin was well tolerated and pulmonary function did not deteriorate. We conclude that severe resistance to subcutaneous insulin does not preclude sufficient absorption of insulin delivered by pulmonary. [source] Short-term sprint interval training increases insulin sensitivity in healthy adults but does not affect the thermogenic response to ,-adrenergic stimulationTHE JOURNAL OF PHYSIOLOGY, Issue 15 2010Jennifer C. Richards Sprint interval training (SIT) and traditional endurance training elicit similar physiological adaptations. From the perspective of metabolic function, superior glucose regulation is a common characteristic of endurance-trained adults. Accordingly, we have investigated the hypothesis that short-term SIT will increase insulin sensitivity in sedentary/recreationally active humans. Thirty one healthy adults were randomly assigned to one of three conditions: (1) SIT (n= 12): six sessions of repeated (4,7) 30 s bouts of very high-intensity cycle ergometer exercise over 14 days; (2) sedentary control (n= 10); (3) single-bout SIT (n= 9): one session of 4 × 30 s cycle ergometer sprints. Insulin sensitivity was determined (hyperinsulinaemic euglycaemic clamp) prior to and 72 h following each intervention. Compared with baseline, and sedentary and single-bout controls, SIT increased insulin sensitivity (glucose infusion rate: 6.3 ± 0.6 vs. 8.0 ± 0.8 mg kg,1 min,1; mean ±s.e.m.; P= 0.04). In a separate study, we investigated the effect of SIT on the thermogenic response to beta-adrenergic receptor (,-AR) stimulation, an important determinant of energy balance. Compared with baseline, and sedentary and single-bout control groups, SIT did not affect resting energy expenditure (EE: ventilated hood technique; 6274 ± 226 vs. 6079 ± 297 kJ day,1; P= 0.51) or the thermogenic response to isoproterenol (6, 12 and 24 ng (kg fat-free mass),1 min,1: %,EE 11 ± 2, 14 ± 3, 23 ± 2 vs. 11 ± 1, 16 ± 2, 25 ± 3; P= 0.79). Combined data from both studies revealed no effect of SIT on fasted circulating concentrations of glucose, insulin, adiponectin, pigment epithelial-derived factor, non-esterified fatty acids or noradrenaline (all P > 0.05). Sixteen minutes of high-intensity exercise over 14 days augments insulin sensitivity but does not affect the thermogenic response to ,-AR stimulation. [source] In vivo activity of 11,-hydroxysteroid dehydrogenase type 1 and free fatty acid-induced insulin resistanceCLINICAL ENDOCRINOLOGY, Issue 4 2005K. Mai Summary Introduction, Free fatty acids (FFAs) induce hepatic insulin resistance and enhance hepatic gluconeogenesis. Glucocorticoids (GCs) also stimulate hepatic gluconeogenesis. The aim of this study was to investigate whether the FFA-induced hepatic insulin resistance is mediated by increased activity of hepatic 11,-hydroxysteroid dehydrogenase type 1 (11,-HSD1), accompanied by elevated hepatic cortisol levels. Methods, Following a 10-h overnight fast, six healthy male volunteers were investigated. A euglycaemic hyperinsulinaemic clamp was performed during lipid or saline infusion. To assess hepatic 11,-HSD1 activity, plasma cortisol levels were measured after oral administration of cortisone acetate during lipid or saline infusion. In addition, 11,-HSD activities were determined in vivo by calculating the urinary ratios of GC metabolites. Results, Lipid infusion increased FFAs (5·41 ± 1·00 vs. 0·48 ± 0·20 mmol/l; P < 0·005) and significantly increased insulin resistance [glucose infusion rate (GIR) 6·02 ± 2·60 vs. 4·08 ± 2·15 mg/kg/min; P < 0·005]. After lipid and saline infusions no changes in 11,-HSD1 activity were found, neither by changes in cortisone acetate to cortisol conversion nor by differences in urinary free cortisol (UFF) or cortisone (UFE), 5,-tetrahydrocortisol (THF), 5,-THF, cortisone (THE), UFF/UFE and (5,-THF + THF)/THE ratios. Conclusions, We found no change in hepatic and whole-body 11,-HSD1 activity during acute FFA-induced insulin resistance. Further studies are necessary to clarify whether 11,-HSD1 in muscle and adipose tissue is influenced by FFAs and whether 11,-HSD1 is involved in other conditions of insulin resistance. [source] Active immunization against leptin fails to affect reproduction and exerts only marginal effects on glucose metabolism in young female goatsJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 7-8 2006H. Sauerwein Summary Approximately 150 days before expected breeding time, 12 female goats (3 months of age) were actively immunized against ovine leptin. Booster injections were given throughout the following year. Control animals (n = 6) were sham-immunized. After the first observed oestrus, a buck was introduced and goats were mated. Blood samples were collected twice weekly and frequent blood sampling series were performed on days ,15, 76, 153 and 286 relative to the first immunization. Nine of the immunized goats developed titres within 3 months and had elevated serum concentrations of leptin compared with controls (p < 0.0001). Hematological parameters and blood chemistry were not affected by the immunization. No differences were detectable in all reproductive parameters recorded. Serum insulin was higher in immunized goats during the frequent blood sampling series of day 287 after the first immunization. Glucose metabolism was investigated during pregnancy using hyperglycaemic and euglycaemic/hyperinsulinaemic clamps. None of the parameters derived from the clamp studies was different (p > 0.05) between the two groups. During the hyperglycaemic clamp there was a trend (p < 0.15) towards increased insulin concentrations in immunized animals whereas glucose infusion rates were not different between the groups. This indicates decreased insulin sensitivity in immunized goats. Our study describes the ontogenesis of serum concentrations of leptin during growth, puberty and first pregnancy and parturition for the caprine species. The effects of the immunization were not detectable or only marginal and the approach aimed at therefore not effective to investigate leptin action in detail. [source] | |||||||||||||