| 1. |
|
|
| 2. |
- Adriani, O., et al.
(författare)
-
Design of an Antimatter Large Acceptance Detector In Orbit (ALADInO)
- 2022
-
Ingår i: Instruments. - : MDPI AG. - 2410-390X. ; 6:2
-
Tidskriftsartikel (refereegranskat)abstract
- A new generation magnetic spectrometer in space will open the opportunity to inves-tigate the frontiers in direct high-energy cosmic ray measurements and to precisely measure the amount of the rare antimatter component in cosmic rays beyond the reach of current missions. We propose the concept for an Antimatter Large Acceptance Detector In Orbit (ALADInO), designed to take over the legacy of direct measurements of cosmic rays in space performed by PAMELA and AMS-02. ALADInO features technological solutions conceived to overcome the current limi-tations of magnetic spectrometers in space with a layout that provides an acceptance larger than 10 m2 sr. A superconducting magnet coupled to precision tracking and time-of-flight systems can provide the required matter–antimatter separation capabilities and rigidity measurement resolution with a Maximum Detectable Rigidity better than 20 TV. The inner 3D-imaging deep calorimeter, designed to maximize the isotropic acceptance of particles, allows for the measurement of cosmic rays up to PeV energies with accurate energy resolution to precisely measure features in the cosmic ray spectra. The operations of ALADInO in the Sun–Earth L2 Lagrangian point for at least 5 years would enable unique revolutionary observations with groundbreaking discovery poten-tials in the field of astroparticle physics by precision measurements of electrons, positrons, and antiprotons up to 10 TeV and of nuclear cosmic rays up to PeV energies, and by the possible unam-biguous detection and measurement of low-energy antideuteron and antihelium components in cosmic rays.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Leppänen, A. -P, et al.
(författare)
-
Cosmogenic Be-7 in air : A complex mixture of production and transport
- 2010
-
Ingår i: Journal of Atmospheric and Solar-Terrestrial Physics. - : Elsevier BV. - 1364-6826 .- 1879-1824. ; 72:13, s. 1036-1043
-
Tidskriftsartikel (refereegranskat)abstract
- The long-time series of Be-7 activity in surface air have been studied with the wavelet analysis technique in order to find coherence between Be-7 activity, theoretical production in the troposphere and climatic indices. The Be-7 activity were obtained from five different locations, Angra in the tropics in Brazil, Skane in mid-latitudes in Southern Sweden, Kiruna in Polar region in Northern Sweden, Loviisa in Southern Finland and Rovaniemi in polar region in Northern Finland. The Be-7 data from the Northern hemisphere sites where tested for coherence with theoretical production of the isotope in troposphere and with the North Atlantic Oscillation index. In the Southern hemisphere separate theoretical production was calculated in order to describe local production and Southern Annular Mode was used as the climatic index. Consistent and significant coherence were found with theoretical production at Skane, Kiruna and Loviisa at time-scales of four years or longer. At Angra and Rovaniemi sites, no coherence was detected between Be-7 theoretical tropospheric production and measured activity at ground level. The coherence between Be-7 data from Skane and Angra and climatic indices is insignificant while data from Northern and Eastern Scandinavia show clear coherence with climatic indices at time-scales of four years or longer. Additionally, significant coherence was found between the cosmic ray induced production and NAO at the time band of 8-12 years whereas the coherence between cosmic ray induced production and SAM was insignificant. This feature implies that the ground level Be-7 activity contain mixed information on both production and transport. This conclusion means that further evaluation through models which enable accurate realistic models that will be investigated in future studies.
|
|
| 8. |
- Pasquali, D., et al.
(författare)
-
BROX haploinsufficiency in familial nonmedullary thyroid cancer
- 2021
-
Ingår i: Journal of Endocrinological Investigation. - : Springer Science and Business Media LLC. - 0391-4097 .- 1720-8386. ; 44, s. 165-171
-
Tidskriftsartikel (refereegranskat)abstract
- Background The familial nonmedullary thyroid cancer (FNMTC) is suspected to be a Mendelian condition in up to 3-8% of thyroid cancers. The susceptibility chromosomal loci and genes of 95% of FNMTC cases remain to be characterized. The inheritance of FNMTC appears to be autosomal dominant with incomplete penetrance and variable expressivity. The finding of the causative gene of FNMTC and the identification of patients at risk that need genetic testing were our aim. Methods We analyzed by whole-exome sequencing patients and non-affected relatives of five families with at least two family members affected by papillary thyroid cancer, selecting for new or extremely rare variants with predicted pathogenic value. Results A family showed, in all three affected members, a new loss-of-function variant (frameshift deletion) in BROX gene at 1q41 that was absent from all internal and external databases. In a second family with three affected relatives, we found an additional new BROX variant. The smaller families presented no variants in BROX or in the other causative genes studied. Conclusions BROX could be a new causative gene for FNMTC. Variants in BROX may result in the haploinsufficiency of a key gene involved in the morphogenesis of MVBs, in the endosomal sorting of cargo proteins, and in EGFR. Functional studies are needed to support this result. The thorough genomic analysis by NGS in all families with three or more affected members should become a routine approach to obtain a comprehensive genetic view and find confirmative second cases.
|
|
| 9. |
- Tura, A., et al.
(författare)
-
An empirical index of insulin sensitivity from short IVGTT: validation against the minimal model and glucose clamp indices in patients with different clinical characteristics
- 2010
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 53:1, s. 144-152
-
Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis Minimal model analysis for insulin sensitivity has been validated against the glucose clamp and is an accepted method for estimating insulin sensitivity from IVGTT. However minimal model analysis requires a 3 h test and relevant expertise to run the mathematical model. The aim of this study was to suggest a simple predictor of minimal model analysis index using only 1 h IVGTT. Methods We studied participants with different clinical characteristics who underwent 3 h regular (n=336) or insulin-modified (n=160) IVGTT, or 1 h IVGTT and euglycaemic-hyperinsulinaemic clamp (n=247). Measures of insulin sensitivity were insulin sensitivity index estimated by minimal model analysis ( SI) and the mean glucose infusion rate (clamp) (M). A calculated S-I (CSI) predictor, CSI alpha x K-G/(Delta AUC(INS)/T), was suggested, based on the calculation of the rate of glucose disappearance K-G and the suprabasal AUC of insulin concentration Delta AUC(INS) over T=40 min. For all the participants, a was assumed equal to the regression line slope between K-G/(Delta AUC(INS)/T) and S-I in control participants. Results CSI and S-I showed high correlation (R-2=0.68-0.96) and regression line slopes of approximately one in the majority of groups. CSI tended to overestimate S-I in type 2 diabetic participants, but results were more reliable when CSI was computed with insulin-modified rather than regular IVGTT. CSI showed behaviours similar to S-I as regards relationships with BMI, acute insulin response and sex. CSI showed good correlation with M (R-2=0.82). Conclusions/interpretation A short test can achieve a good approximation of minimal model analysis and clamp insulin sensitivity. The importance of a method such as CSI is that it allows analysis of IVGTT datasets with samples limited to 1 h.
|
|
| 10. |
- Ahlkvist, Linda, et al.
(författare)
-
Synergism by individual macronutrients explains the marked early GLP-1 and islet hormone responses to mixed meal challenge in mice
- 2012
-
Ingår i: Regulatory Peptides. - : Elsevier. - 0167-0115 .- 1873-1686. ; 178:1-3, s. 29-35
-
Tidskriftsartikel (refereegranskat)abstract
- Apart from glucose, proteins and lipids also stimulate incretin and islet hormone secretion. However, the glucoregulatory effect of macronutrients in combination is poorly understood. We therefore developed an oral mixed meal model in mice to 1) explore the glucagon-like peptide-1 (GLP-1) and islet hormone responses to mixed meal versus isocaloric glucose, and 2) characterize the relative contribution of individual macronutrients to these responses. Anesthetized C57BL/6J female mice were orally gavaged with 1) a mixed meal (0.285 kcal; glucose, whey protein and peanut oil; 60/20/20% kcal) versus an isocaloric glucose load (0.285 kcal), and 2) a mixed meal (0.285 kcal) versus glucose, whey protein or peanut oil administered individually in their mixed meal caloric quantity, i.e., 0.171, 0.055 and 0.055 kcal, respectively. Plasma was analyzed for glucose, insulin and intact GLP-1 before and during oral challenges. Plasma glucose was lower after mixed meal versus after isocaloric glucose ingestion. In spite of this, the peak insulin response (P=0.02), the peak intact GLP-1 levels (P=0.006) and the estimated β-cell function (P=0.005) were higher. Furthermore, the peak insulin (P=0.004) and intact GLP-1 (P=0.006) levels were higher after mixed meal ingestion than the sum of responses to individual macronutrients. Compared to glucose alone, we conclude that there is a marked early insulin response to mixed meal ingestion, which emanates from a synergistic, rather than an additive, effect of the individual macronutrients in the mixed meal and is in part likely caused by increased levels of GLP-1.
|
|
| 11. |
- Ahrén, Bo, et al.
(författare)
-
A Novel Approach to Assess Insulin Sensitivity Reveals No Increased Insulin Sensitivity in Mice with a Dominant-Negative Mutant Hepatocyte Nuclear Factor-1{alpha}
- 2006
-
Ingår i: American Journal of Physiology: Regulatory, Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 291:1, s. 131-137
-
Tidskriftsartikel (refereegranskat)abstract
- In phenotype experiments in mice, determination of dynamic insulin sensitivity often uses the insulin tolerance test. However, the interpretation of this test is complicated by the counterregulation occurring at low glucose. To overcome this problem, we determined the dynamic insulin sensitivity after inhibition of endogenous insulin secretion by diazoxide (25 mg/kg) in association with intravenous administration of glucose plus insulin (the DSGIT technique). Estimation of insulin sensitivity index (SI) by this technique showed good correlation to SI from a regular intravenous glucose tolerance test (r = 0.87; P < 0.001; n = 15). With DSGIT, we evaluated dynamic insulin sensitivity in mice with a rat insulin promoter (beta-cell-targeted) dominant-negative mutation of hepatic nuclear factor (HNF)-1{alpha} [RIP-DN HNF-1{alpha} (Tg) mice]. When insulin was administered exogenously at the same dose in Tg and wild-type (WT) mice, plasma insulin levels were higher in WT, indicating an increased insulin clearance in Tg mice. When the diazoxide test was used, different doses of insulin were therefore administered (0.1 and 0.15 U/kg in WT and 0.2 and 0.25 U/kg in Tg) to achieve similar insulin levels in the groups. Minimal model analysis showed that SI was the same in the two groups (0.78 ± 0.21 x 10–4 min·pmol–1·l–1 in WT vs. 0.60 ± 0.11 in Tg; P = 0.45) as was the glucose elimination rate (P = 0.27). We conclude that 1) the DSGIT technique determines the in vivo dynamic insulin action in mice, 2) insulin clearance is increased in Tg mice, and 3) chronic islet dysfunction in RIP-DN HNF-1{alpha} mice is not compensated with increased insulin sensitivity.
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Ahrén, Bo, et al.
(författare)
-
Effects of conjugated linoleic acid plus n-3 polyunsaturated fatty acids on insulin secretion and estimated insulin sensitivity in men.
- 2009
-
Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 1476-5640 .- 0954-3007. ; Sep 3, s. 778-786
-
Tidskriftsartikel (refereegranskat)abstract
- Background/Objectives:Dietary addition of either conjugated linoleic acid (CLA) or n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) has been shown to alter adiposity and circulating lipids, risk markers of cardiovascular diseases. However, CLA may decrease insulin sensitivity, an effect that may be reversed by n-3 LC-PUFA. Thus, the potential of CLA plus n-3 LC-PUFA to affect insulin secretion and sensitivity in non-diabetic young and old, lean and obese subjects was tested.Subjects/Methods:CLA (3 g daily) plus n-3 LC-PUFA (3 g daily) or control oil (6 g daily) was given to lean (n=12; BMI 20-26 kg/m(2)) or obese (n=10; BMI 29-35 kg/m(2)) young (20-37 years old) or lean (n=16) or obese (n=11) older men (50-65 years) for 12 weeks. The study had a double-blind, placebo-controlled randomized crossover design, and primary end points were insulin secretion and sensitivity during a standardized meal test, evaluated by modeling glucose, insulin and C-peptide data.Results:The combination was well tolerated. There was no significant difference in fasting levels of glucose, insulin or C-peptide after CLA/n-3 LC-PUFA treatment compared with control oil. Neither insulin secretion nor estimated sensitivity was affected by CLA/n-3 LC-PUFA in lean or obese young subjects or in older lean subjects. However, in older obese subjects, estimated insulin sensitivity was reduced with CLA/n-3 LC-PUFA compared with control (P=0.024).Conclusions:The results do not support beneficial effects of CLA/n-3 LC-PUFA for beta-cell dysfunction or insulin resistance in humans but suggest that insulin sensitivity in older obese subjects is reduced.European Journal of Clinical Nutrition advance online publication, 3 September 2008; doi:10.1038/ejcn.2008.45.
|
|
| 15. |
- Ahrén, Bo, et al.
(författare)
-
Improved meal-related insulin processing contributes to the enhancement of B-Cell function by the DPP-4 inhibitor vildagliptin in patients with type 2 diabetes
- 2007
-
Ingår i: Hormone and Metabolic Research. - : Georg Thieme Verlag KG. - 1439-4286 .- 0018-5043. ; 39:11, s. 826-829
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the contribution of insulin processing to the improved meal-related B-cell function previously shown with the DPP-4 inhibitor vildagliptin. Fifty-five patients with type 2 diabetes (56.5 +/- 1.5 years; BMI=29.6 +/- 0.5kg/m(2); FPG = 9.9 +/- 0.2 mmol/l; HbA1c=7.7 +/- 0.1 %) were studied: 29 pateients were treated with vildagliptin and 26 patients with placebo, both added to an ongoing metformin regimen (1.5-3.0g/day). A standardized breakfast was given at baseline and after 52 weeks of treatment, and proinsulin related to insulin secretion was measured with C-peptide in the fasting and postprandial (over 4h post-meal) states to evaluate B-cell function. The between-treatment difference (vildaglip-tin-placebo) in mean change from baseline in fasting proinsulin to C-peptide ratio (fastP/C) was -0.007 +/- 0.009 (p=0.052). Following the standard breakfast, 52 weeks of treatment with vildagliptin significantly decreased the dynamic proinsulin to C-peptide ratio (dynP/C) relative to placebo by 0.010 +/- 0.008 (p = 0.037). Importantly, when the P/C was expressed in relation to the glucose stimulus (i.e., the fasting glucose and glucose AUC(0-240min), respectively), the P/C relative to glucose was significantly reduced with vildagliptin vs. placebo, both in the fasting state (p = 0.023) and postprandially (p = 0.004). In conclusion, a more efficient B-cell insulin processing provides further evidence that vildagliptin treatment ameliorates abnormal B-cell function in patients with type 2 diabetes.
|
|
| 16. |
- Ahrén, Bo, et al.
(författare)
-
Insufficient islet compensation to insulin resistance vs. reduced glucose effectiveness in glucose-intolerant mice
- 2002
-
Ingår i: American Journal of Physiology: Endocrinology and Metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 283:4, s. 738-744
-
Tidskriftsartikel (refereegranskat)abstract
- This study evaluated the relative contribution of insulin-dependent mechanisms vs. mechanisms independent on dynamic insulin for glucose intolerance induced by high-fat diet. C57BL/6J mice underwent a frequently sampled intravenous glucose tolerance test (1 g/kg glucose) at 1 wk and 1, 3, and 10 mo after initiation of a high-fat diet (58% fat; control diet 11% fat) to measure glucose effectiveness (S-G) and disposition index (DI), i.e., insulin sensitivity (SI) times early or total insulin secretion. Glucose disappearance (KG) and SI were reduced in high-fat-fed mice at all time points. Total (50 min) insulin secretion was sufficiently increased at all time points to compensate for the reduced SI, as judged by normal DI50 min. In contrast, early (10 min) insulin secretion was not sufficiently increased; DI10 min was reduced after 1, 3, and 10 mo. SG was reduced after 1 wk; the reduction persisted throughout the study period. Thus glucose intolerance induced by high-fat diet is, in early phases, solely explained by reduced glucose effectiveness, whereas insufficient early insulin secretion is of importance after long-term feeding.
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
- Ahrén, Bo, et al.
(författare)
-
Signals adapting the beta cells to changes in insulin sensitivity
- 2003
-
Ingår i: The metabolic syndrome: diabetes, obesity, hyperlipidemia and hypertension. Proceedings of the 8th European Symposium on Metabolism. - 0531-5131. ; 1253, s. 105-113
-
Konferensbidrag (refereegranskat)abstract
- Insulin sensitivity and secretion are related in a curvilinear inverse asymptotic function. However, the signaling factors mediating this relation are not known. In this study, we explored whether circulating glucose, lipids or two adipocyte-derived hormones, leptin and adiponectin, are related to the curvilinear function between insulin sensitivity and secretion in subjects with normal glucose tolerance. Thereby, insulin secretion (2-5-min insulin response to intravenous arginine) and insulin sensitivity (euglycemic, hyperinsulinemic clamp) were established in 68 healthy women, aged 61 years. We confirmed the curvilinear relation between insulin sensitivity and insulin secretion (r = -0.71, P < 0.001). To quantify the ability of the beta cells to secrete insulin for balancing a change in insulin sensitivity, we introduce the beta cell compensation index (BCI) by dividing insulin secretion by insulin sensitivity. This index correlated significantly with circulating triglycerides, leptin and adiponectin as well as BMI, but not fasting or 2-h glucose. A multivariate stepwise regression analysis using these variables as independent variables and lg BCI as the dependent variable revealed that leptin (r = 0.54, P < 0.001) and adiponectin (r = -0.33, P = 0.008) independently contributed to lg BCI (R-2 of the model = 0.19m, P = 0.038). The study, therefore, suggests that adipocyte-derived hormones contribute to the beta cell compensation to insulin resistance. (C) 2002 Elsevier Science B.V. All rights reserved.
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
- Gomes, J., et al.
(författare)
-
An overview of project COMPOUND: Cooperative communications and positioning in mobile underwater networks
- 2012
-
Ingår i: 2012 Future Network and Mobile Summit, FutureNetw 2012. - 9781905824304 ; , s. Article number6294172-
-
Konferensbidrag (refereegranskat)abstract
- One of the challenges faced by future networks is to integrate heterogeneous segments whose protocols are optimized for very different conditions. This work provides an overview of project COMPOUND, which tackles problems in this class to interface an underwater acoustic network comprising both static and mobile nodes to the Internet. The main goal is to create value and foster new applications in a niche but strategically important area by making the data and assets in the network easily available to a wide community. This will reduce the time, effort, and cost needed to customize the network to suit a specific need. A key insight in COMPOUND is to extensively exploit knowledge of node positions, including submerged ones with no access to GPS, to configure the network parameters at multiple levels, from the Internet gateway down to a node's physical layer. In turn, positioning is derived from observed data traffic on the network and collaborative exchanges between nodes, resulting in a system that tightly integrates positioning and communications. This paper discusses the proposed approach within the scope of current research on underwater acoustic communications and networking, describes application scenarios, envisaged technical solutions, planned developments, and identifies some of the possible impacts of this work. © 2012 IIMC Ltd.
|
|
| 23. |
- Mari, A, et al.
(författare)
-
Comparative evaluation of simple insulin sensitivity methods based on the oral glucose tolerance test
- 2005
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 48:4, s. 748-751
-
Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: We compared five surrogate insulin sensitivity ( IS) methods against the euglycaemic - hyperinsulinaemic clamp. These methods were the homeostasis model assessment (HOMA) and four methods based on the OGTT (OGIS, MCRest, ISIcomp, SIORAL). Methods: We compared these IS methods against the clamp (0.28 nmol center dot min(-1) center dot m(-2) insulin infusion) M value in 147 women ( 58 - 61 years; BMI 19 - 38 kg/m(2); 116 NGT, 25 IFG/IGT, six type 2 diabetic), by evaluating the correlation coefficient with M. We also tested the ability to reproduce the relationships between IS and typical IS correlates ( BMI, fasting insulin, insulin to glucose OGTT area ratio and fasting, 2 h and mean glucose) by means of the "discrepancy index" D, in which ( 1) D=0 if the correlation between IS and the variable of interest is as with the clamp, ( 2) D is smaller than 0 if the correlation is overestimated, and ( 3) D is greater than 0 if underestimated. Results: All IS methods correlated with M ( r=0.57 - 0.83, p< 0.0001); for MCRest the relationship was markedly curvilinear. All IS measures correlated with the considered variables (r= 0.29 - 0.94, p< 0.0005); however, no method had D approximate to 0 for all variables. The best surrogates of M were OGIS ( one D. 0) and MCRest ( two D. 0); the other methods either under- or overestimated the degree of correlation three or more D. 0), in particular with fasting insulin (HOMA: D=- 57%; ISIcomp: D=- 36%) and BMI ( HOMA: D=- 14%; ISIcomp: D=- 14%; SiORAL: D=- 11%). Conclusions/interpretation: AllIS methods were correlated with M. OGIS and MCRest were preferable to the other methods and in particular to HOMA for reproducing relationships with the independent variables.
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
- Pacini, G., et al.
(författare)
-
Methods and Models for Metabolic Assessment in Mice
- 2013
-
Ingår i: Journal of Diabetes Research. - : Hindawi Limited. - 2314-6753 .- 2314-6745.
-
Tidskriftsartikel (refereegranskat)abstract
- The development of new therapies for the treatment of type 2 diabetes requires robust, reproducible and well validated in vivo experimental systems. Mice provide the most ideal animal model for studies of potential therapies. Unlike larger animals, mice have a short gestational period, are genetically similar, often give birth to many offspring at once and can be housed as multiple groups in a single cage. The mouse model has been extensively metabolically characterized using different tests. This report summarizes how these tests can be executed and how arising data are analyzed to confidently determine changes in insulin resistance and insulin secretion with high reproducibility. The main tests for metabolic assessment in the mouse reviewed here are the glucose clamp, the intravenous and the oral glucose tolerance tests. For all these experiments, including some commonly adopted variants, we describe: (i) their performance; (ii) their advantages and limitations; (iii) the empirical formulas and mathematical models implemented for the analysis of the data arising from the experimental procedures to obtain reliable measurements of peripheral insulin sensitivity and beta cell function. Finally, a list of previous applications of these methods and analytical techniques is provided to better comprehend their use and the evidences that these studies yielded.
|
|
| 29. |
|
|
| 30. |
- Sjögren, Klara, 1970, et al.
(författare)
-
Liver-derived IGF-I is of importance for normal carbohydrate and lipid metabolism.
- 2001
-
Ingår i: Diabetes. - 0012-1797. ; 50:7, s. 1539-45
-
Tidskriftsartikel (refereegranskat)abstract
- IGF-I is important for postnatal body growth and exhibits insulin-like effects on carbohydrate metabolism. The function of liver-derived IGF-I is still not established, although we previously demonstrated that liver-derived IGF-I is not required for postnatal body growth. Mice whose IGF-I gene in the liver was inactivated at 24 days of age were used to investigate the long-term role of liver-derived IGF-I for carbohydrate and lipid metabolism. Serum levels of leptin in these mice were increased by >100% at 3 months of age, whereas the fat mass of the mice was decreased by 25% at 13 months of age. The mice became markedly hyperinsulinemic and yet normoglycemic, indicating an adequately compensated insulin resistance. Furthermore, they had increased serum levels of cholesterol. We conclude that liver-derived IGF-I is of importance for carbohydrate and lipid metabolism.
|
|
| 31. |
- Thomaseth, K., et al.
(författare)
-
Glucagon-like peptide-1 accelerates the onset of insulin action on glucose disappearance in mice
- 2007
-
Ingår i: American Journal of Physiology: Endocrinology and Metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 292:6, s. 1808-1814
-
Tidskriftsartikel (refereegranskat)abstract
- Glucagon- like peptide-1 ( GLP-1) plays a significant role in glucose homeostasis through its incretin effect on insulin secretion. However, GLP-1 also exhibits extrapancreatic actions, and in particular its possible influences on insulin sensitivity are controversial. To study the dynamic action of GLP-1 on insulin sensitivity, we applied advanced statistical modeling methods to study glucose disappearance in mice that underwent intravenous glucose tolerance test with administration of GLP-1 at various dose levels. In particular, the minimal model of glucose disappearance was exploited within a population estimation framework for accurate detection of relationships between glucose disappearance parameters and GLP-1. Minimal model parameters were estimated from glucose and insulin data collected in 209 anesthetized normal mice after intravenous injection of glucose ( 1 g/ kg) alone or with GLP- 1 ( 0.03 - 100 nmol/ kg). Insulin secretion markedly increased, as expected, with increasing GLP-1 dose. However, minimal model- derived indexes, i. e., insulin sensitivity and glucose effectiveness, did not significantly change with GLP-1 dose. Instead, fractional turnover rate of insulin action [ P-2 = 0.0207 +/- 24.3% ( min) at zero GLP-1 dose] increased steadily with administered GLP-1 dose, with significant differences at 10.4 nmol/ kg ( P-2 = 0.040 +/- 15.5%, P = 0.0046) and 31.2 nmol/ kg ( P-2 = 0.050 +/- 29.2%, P = 0.01). These results show that GLP-1 influences the dynamics of insulin action by accelerating insulin action following glucose challenge. This is a novel mechanism contributing to the glucose- lowering action of GLP-1.
|
|
