The perilipin 2 (PLIN2) gene Ser251Pro missense mutation is associated with reduced insulin secretion and increased insulin sensitivity in Italian obese subjects

2015 ◽  
Vol 32 (6) ◽  
pp. 550-556 ◽  
Author(s):  
Federica Sentinelli ◽  
Danila Capoccia ◽  
Michela Incani ◽  
Laura Bertoccini ◽  
Anna Severino ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Missense Mutation ◽  
Obese Subjects ◽  
Perilipin 2

Insulin sensitivity, insulin secretion, and glucose effectiveness in obese subjects: A minimal model analysis

Metabolism ◽  
1995 ◽  
Vol 44 (11) ◽  
pp. 1397-1400 ◽  
Author(s):  
Ataru Taniguchi ◽  
Yoshikatu Nakai ◽  
Kentaro Doi ◽  
Hiroaki Fukuzawa ◽  
Mitsuo Fukushima ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Minimal Model ◽  
Model Analysis ◽  
Glucose Effectiveness ◽  
Obese Subjects

scholarly journals Salicylates Increase Insulin Secretion in Healthy Obese Subjects

2008 ◽  
Vol 93 (7) ◽  
pp. 2523-2530 ◽  
Author(s):  
José-Manuel Fernández-Real ◽  
Abel López-Bermejo ◽  
Ana-Belén Ropero ◽  
Sandra Piquer ◽  
Angel Nadal ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Treatment Period ◽  
Islets Of Langerhans ◽  
Glucose Concentration ◽  
Human Islets ◽  
Serum Glucose ◽  
Obese Subjects ◽  
Healthy Obese

Abstract Context: Conflicting results on the effects of salicylates on glucose tolerance in subjects with normal glucose tolerance or type 2 diabetes have been reported. Objective: The objective of the study was to investigate the effects of a salicylate derivative (triflusal) on insulin sensitivity and insulin secretion. Design, Setting, and Participants: This was a double-blind, randomized, crossover study with three treatment periods corresponding to two dose levels of triflusal and placebo in healthy obese subjects. Main Outcome Measures: Insulin sensitivity and insulin secretion, evaluated through frequently sampled iv glucose tolerance test that was performed after each treatment period, were measured. Insulin secretion was also evaluated in vitro in mice and human islets of Langerhans. Results: The administration of triflusal led to decreased fasting serum glucose concentration in the study subjects. Insulin sensitivity did not significantly change after each treatment period. Insulin secretion, however, significantly increased in a dose-dependent fashion after each triflusal treatment period. The administration of 800 μm of the main triflusal metabolite to whole mice islets of Langerhans led to a sustained increase in intracellular calcium concentration level. This was followed by a significantly increase in insulin secretion. In human islets, 200 μm of 2-hydroxy-4-trifluoromethylbenzoic acid was sufficient to increase insulin release. Conclusions: The administration of a salicylate compound led to lowering of serum glucose concentration. We suggest that this effect was mediated through increased insulin secretion induced by salicylate directly on the β-cell.

scholarly journals The ingestion of saturated fatty acid triacylglycerols acutely affects insulin secretion and insulin sensitivity in human subjects

2004 ◽  
Vol 92 (6) ◽  
pp. 895-903 ◽  
Author(s):  
Melania Manco ◽  
Alessandro Bertuzzi ◽  
Serenella Salinari ◽  
Antonino Scarfone ◽  
Menotti Calvani ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Human Subjects ◽  
Saturated Fat ◽  
Normal Weight ◽  
Insulin Clearance ◽  
Water Load ◽  
Obese Subjects ◽  
Insulin Secretion Rate ◽  
Saturated Fat Intake

To assess the effects of acute dietary saturated fat intake on glucose-induced insulin secretion rate (ISR), measured by the C-peptide deconvolution method, and on insulin clearance and sensitivity, five obese and five normal-weight women (controls) were studied after either a 100g oral butter load or a 100ml water load. At 120min after the oral load a hyperglycaemic clamp was performed over 180min. A dramatic increase of ISR occurred after butter compared with the water challenge in the controls (1305·6 (SE 124·1) v. 616·1 (SE 52·5) pmol/min; P<0·01) and to a lesser degree in the obese subjects (1975·0 (SE 44·1) v. 1417·5 (SE 56·0) pmol/min; P<0·05). Insulin sensitivity was impaired after butter (0·60×10−2 (SE 0·11×10−2) v. 2·26×10−2 (SE 0·32×10−2) ml/min per kgFFM per (pmol/l); P<0·01) in the controls but not in the obese group. Insulin clearance during the clamp was reduced after butter compared with after the water load only in the controls (0·89 (SE 0·22) v. 1·70 (SE 0·15) litres/min; P<0·01). The data are consistent with the hypothesis that acute excess lipid availability may lead to a compensatory elevation in glucose-induced insulin secretion as a result of the decline in insulin sensitivity and a reduced insulin clearance.

scholarly journals Insulin Sensitivity Measured with the Oral Minimal Model is lower in Obese Subjects Who Report omitting their Breakfast

2019 ◽  
pp. 134-145
Author(s):  
Brun JF ◽  
Delbos C ◽  
Gimet F ◽  
Raynaud de Mauverger E ◽  
Mercier J
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Minimal Model ◽  
Cross Sectional Study ◽  
Oral Glucose ◽  
Sectional Study ◽  
Cross Sectional ◽  
Obese Subjects ◽  
Oral Minimal Model

Introduction: Omitting the breakfast has been reported to promote weight gain and to impair insulin sensitivity. However this latter effect was only assessed with simple surrogates. We thus aimed at verifying if insulin sensitivity is lowered in individuals who omit their breakfast with a more quantitative assessment, using the “Oral Minimal Model” (OMM) i.e., an extension of Bergman’s minimal model to oral glucose tolerance-tests, in a cross-sectional study of a population exhibiting the full range of body mass indices.Materials and methods: We selected on our database of patients, explored for weight and/or eating disorders, 27 individuals omitting their breakfast (defined on the basis of an alimentary standardized questionnaire) and compared them to 103 matched subjects taking a hyperglucidic breakfast. The breakfast was analyzed with the OMM for the assessment of insulin sensitivity. Insulin secretion was assessed with a previously reported procedure, allowing the calculation of the parameters of phase 1 and 2 of insulin secretion of Cobelli and Mari’s models. In addition, it is already known that Mari’s model provides an index of post stimulatory potentiation of insulin secretion. Disposition indices (product of SI and insulin secretion parameters) were also determined.Results: In the 27 subjects omitting their breakfast compared to the 103 matched subjects the difference in insulin sensitivity was not found. No difference in insulin secretion parameters is detected. Homeostasis between insulin secretion and insulin sensitivity appears to be functional. However when splitting the sample in categories of BMI the expected difference appears in the range 30-40. In this subgroup (Omitting (n=9) BMI: 35.4±0.99 vs. non-omitting (n=47) BMI: 34.1±0.37 kg/m²) insulin sensitivity was lower in individuals omitting their breakfast (4.32 10-4 min-1/(μU/ml)± 0.94 vs. 9.33±1.84, p=0.03). Despite a slight increase in insulin levels and in the overall insulin secretion rate, a decrease in potentiation and in disposition index was evidenced in individuals omitting their breakfast. The lowering effect of omitting the breakfast on insulin sensitivity is thus evidenced in obese subjects in this sample (but not in those with a BMI below 30). This impairment in insulin sensitivity resulted in a decrease of glucose tolerance by 34%. This finding, based on a cross-sectional study but using a sophisticated measurement, is in agreement with the previous report that omission of the breakfast may induce resistance to insulin. It suggests that the worsening effect on SI that was experimentally found in an interventional study in healthy women becomes important enough in obese subjects to be detected in a cross-sectional study, and that this effect associates a decrease in SI and an incomplete adaptation of insulin release to this reduction in SI, and thus a decrease in glucose tolerance.

scholarly journals The Gly482Ser Missense Mutation of the Peroxisome Proliferator-Activated Receptor γ Coactivator-1α (PGC-1α) Gene Associates with Reduced Insulin Sensitivity in Normal and Glucose-Intolerant Obese Subjects

2005 ◽  
Vol 21 (4) ◽  
pp. 175-180 ◽  
Author(s):  
Marzia Fanelli ◽  
Emanuela Filippi ◽  
Federica Sentinelli ◽  
Stefano Romeo ◽  
Mara Fallarino ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Missense Mutation ◽  
Peroxisome Proliferator ◽  
Primary Role ◽  
Peroxisome Proliferator Activated Receptor ◽  
Increased Risk ◽  
Wide Range ◽  
Obese Subjects

Among the putative candidate genes for insulin resistance, the peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is a transcriptional coactivator of PPARγ and α, regulating a wide range of processes involved in energy production and utilization, such as thermogenesis, liver gluconeogenesis, glucose uptake in muscle. In population studies a Gly482Ser substitution in PGC-1α has been reported to be associated with increased risk of type diabetes 2 and insulin resistance. In the present study we have analysed the association between the Gly482Ser missense mutation of the PGC-1α gene and insulin sensitivity and glucose tolerance in a population of obese non-diabetic subjects. The Gly482Ser SNPs was detected by PCR-RFLP in a cohort of 358 Caucasian obese subjects (223 with normal glucose tolerance (NGT) and 125 with impaired glucose tolerance (IGT). We observed a significant association (p < 0.007) between carriers of the Gly482Ser variant of the PGC-1α gene and insulin resistance measured by HOMAIR. Multivariate analysis confirmed that the Gly482Ser SNP was a significant (p < 0.02) determinant of decreased insulin sensitivity, independently from other well-known modulators of insulin action. In conclusion, we have found significant association between the Gly482Ser variant of the PGC-1α gene and reduced insulin sensitivity in obese subjects. This association resulted independent from all other known modulators of insulin resistance, and suggests a primary role for the PGC-1α gene on the genetic susceptibility to insulin resistance in obesity.

scholarly journals β-Cell Sensitivity to GLP-1 in Healthy Humans Is Variable and Proportional to Insulin Sensitivity

2015 ◽  
Vol 100 (6) ◽  
pp. 2489-2496 ◽  
Author(s):  
Benedikt A. Aulinger ◽  
Torsten P. Vahl ◽  
Hilary E. Wilson-Pérez ◽  
Ron L. Prigeon ◽  
David A. D'Alessio
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Healthy Subjects ◽  
Normal Glucose Tolerance ◽  
Β Cell ◽  
Cell Sensitivity ◽  
Entire Study ◽  
Healthy Humans ◽  
Obese Subjects

Context: Glucagon-like peptide-1 (GLP-1) is an insulinotropic factor made in the gastrointestinal tract that is essential for normal glucose tolerance. Infusion of GLP-1 increases insulin secretion in both diabetic and nondiabetic humans. However, the degree to which people vary in their β-cell sensitivity to GLP-1 and the factors contributing to this variability have not been reported. Objective: The objective was to measure the sensitivity of insulin secretion to GLP-1 in cohorts of lean and obese subjects across a broad range of insulin sensitivity. Methods: Insulin secretion was measured during clamped hyperglycemia (7.2 mmol/L) and graded GLP-1 infusion in young, healthy subjects, and GLP-1 sensitivity was computed from the insulin secretion rate (ISR) during progressive increases in plasma GLP-1. Results: All subjects had fasting glucose values &lt;5.2 mm. The obese subjects were insulin resistant compared to the lean group (homeostasis model of assessment 2 for insulin resistance: obese, 2.6 ± 0.5; lean, 0.8 ± 0.1; P &lt; .001). ISR increased linearly in both cohorts with escalating doses of GLP-1, but the slope of ISR in response to GLP-1 was greater in the obese than in the lean subjects (obese, 0.17 ± 0.03 nmol/min/pm; lean, 0.05 ± 0.01 nmol/min/pm; P &lt; .001). There was a significant association of β-cell GLP-1 sensitivity and insulin resistance (r = 0.83; P &lt; .001), and after correction for homeostasis model of assessment 2 for insulin resistance, the slopes of ISR vs GLP-1 concentration did not differ in the two cohorts (obese, 0.08 ± 0.01; lean, 0.08 ± 0.01; P = .98). However, within the entire study group, β-cell GLP-1 sensitivity corrected for insulin resistance varied nearly 10-fold. Conclusions: Insulin secretion in response to GLP-1 is proportional to insulin resistance in healthy subjects. However, there is considerable variability in the sensitivity of the β-cell to GLP-1 that is independent of insulin sensitivity.

Insulin secretion and insulin sensitivity in normal pregnancy and gestational diabetes mellitus

2003 ◽  
Vol 17 (2) ◽  
pp. 137-142 ◽  
Author(s):  
E. Akbay ◽  
M. B. Tıras ◽  
I. Yetkin ◽  
F. Törüner ◽  
R. Ersoy ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Normal Pregnancy
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