scholarly journals PPARGC1A Gene Promoter Methylation as a Biomarker of Insulin Secretion and Sensitivity in Response to Glucose Challenges

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2790
Author(s):  
José L. Santos ◽  
Bernardo J. Krause ◽  
Luis Rodrigo Cataldo ◽  
Javier Vega ◽  
Francisca Salas-Pérez ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Gene Promoter ◽  
Tolerance Test ◽  
Proximal Promoter ◽  
Oral Glucose ◽  
Intravenous Glucose ◽  
Cpg Sites

Methylation in CpG sites of the PPARGC1A gene (encoding PGC1-α) has been associated with adiposity, insulin secretion/sensitivity indexes and type 2 diabetes. We assessed the association between the methylation profile of the PPARGC1A gene promoter gene in leukocytes with insulin secretion/sensitivity indexes in normoglycemic women. A standard oral glucose tolerance test (OGTT) and an abbreviated version of the intravenous glucose tolerance test (IVGTT) were carried out in n = 57 Chilean nondiabetic women with measurements of plasma glucose, insulin, and C-peptide. Bisulfite-treated DNA from leukocytes was evaluated for methylation levels in six CpG sites of the proximal promoter of the PPARGC1A gene by pyrosequencing (positions -816, -783, -652, -617, -521 and -515). A strong correlation between the DNA methylation percentage of different CpG sites of the PPARGC1A promoter in leukocytes was found, suggesting an integrated epigenetic control of this region. We found a positive association between the methylation levels of the CpG site -783 with the insulin sensitivity Matsuda composite index (rho = 0.31; p = 0.02) derived from the OGTT. The CpG hypomethylation in the promoter position -783 of the PPARGC1A gene in leukocytes may represent a biomarker of reduced insulin sensitivity after the ingestion of glucose.

scholarly journals Postnatal ontogeny of glucose homeostasis and insulin action in sheep

2004 ◽  
Vol 286 (6) ◽  
pp. E1050-E1059 ◽  
Author(s):  
K. L. Gatford ◽  
M. J. De Blasio ◽  
P. Thavaneswaran ◽  
J. S. Robinson ◽  
I. C. McMillen ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Early Adulthood ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Postnatal Ontogeny ◽  
Intravenous Glucose ◽  
Female Sheep

Glucose tolerance declines with maturation and aging in several species, but the time of onset and extent of changes in insulin sensitivity and insulin secretion and their contribution to changes in glucose tolerance are unclear. We therefore determined the effect of maturation on glucose tolerance, insulin secretion, and insulin sensitivity in a longitudinal study of male and female sheep from preweaning to adulthood, and whether these measures were related across age. Glucose tolerance was assessed by intravenous glucose tolerance test (IVGTT, 0.25 g glucose/kg), insulin secretion as the integrated insulin concentration during IVGTT, and insulin sensitivity by hyperinsulinemic-euglycemic clamp (2 mU insulin·kg−1·min−1). Glucose tolerance, relative insulin secretion, and insulin sensitivity each decreased with age ( P < 0.001). The disposition index, the product of insulin sensitivity, and various measures of insulin secretion during fasting or IVGTT also decreased with age ( P < 0.001). Glucose tolerance in young adult sheep was independently predicted by insulin sensitivity ( P = 0.012) and by insulin secretion relative to integrated glucose during IVGTT ( P = 0.005). Relative insulin secretion before weaning was correlated positively with that in the adult ( P = 0.023), whereas glucose tolerance, insulin sensitivity, and disposition indexes in the adult did not correlate with those at earlier ages. We conclude that glucose tolerance declines between the first month of life and early adulthood in the sheep, reflecting decreasing insulin sensitivity and absence of compensatory insulin secretion. Nevertheless, the capacity for insulin secretion in the adult reflects that early in life, suggesting that it is determined genetically or by persistent influences of the perinatal environment.

Insulin sensitivity in women: a comparison among values derived from intravenous glucose tolerance tests with different sampling frequency, oral glucose tolerance test or fasting

2001 ◽  
pp. 281-287 ◽  
Author(s):  
A Cagnacci ◽  
S Arangino ◽  
A Renzi ◽  
P Cagnacci ◽  
A Volpe
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Oral Glucose Tolerance Test ◽  
Glucose Tolerance Test ◽  
Polycystic Ovary ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Intravenous Glucose ◽  
Intravenous Glucose Tolerance

OBJECTIVE: To determine the correlation between insulin sensitivity (S(I)) obtained by the minimal model method applied to a frequently sampled (n=33) intravenous glucose tolerance test (FSIGT(33)), and values obtained by reduced FSIGTs, oral glucose tolerance test (OGTT), or fasting. DESIGN: Retrospective analysis on tests performed in prospective studies. METHODS: A total of 78 FSIGT(33), and 59 OGTT were performed in non-diabetic women of which 10 were young cyclic females in the early follicular menstrual phase, 10 were young non-obese subjects with polycystic ovary syndrome (PCOS) and 30 were in post-menopause. Some of these individuals were investigated both prior to and during specified treatments. FSIGT(33) was transformed into FSIGT(22) and FSIGT(12) by removing samples from the analysis. Values of SI derived from reduced FSIGTs or calculations performed on glucose and insulin values observed in fasting conditions and/or during OGTT were related to those of FSIGT(33). RESULTS: S(I) values derived from FSIGT(33) were highly correlated with those derived from FSIGT(22) (r=0.965) or FSIGT(12) (r=0.955), but were only weakly correlated with those derived from fasting or OGTT calculations (r below 0.5). Between-group (PCOS vs normal) or within-group (prior to and during treatment) comparisons showed that reduced FSIGTs were only slightly less powerful than FSIGT(33) in detecting differences in S(I). CONCLUSIONS: In non-diabetic women, reduced FSIGTs but not calculations based on fasting or OGTT values may be used in place of FSIGT(33) to document S(I) and its variation.

scholarly journals Antidepressant Effects on Insulin Sensitivity and Proinflammatory Cytokines in the Depressed Males

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Yi-Chyan Chen ◽  
Wei-Win Lin ◽  
Yu-Jung Chen ◽  
Wei-Chung Mao ◽  
Yi-Jen Hung
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Rating Scale ◽  
Glucose Tolerance Test ◽  
Antidepressant Treatment ◽  
Insulin Response ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Intravenous Glucose ◽  
Testing Procedures

Growing evidence suggests that mood disorder is associated with insulin resistance and inflammation. Thus the effects of antidepressants on insulin sensitivity and proinflammatory responses will be a crucial issue for depression treatment. In this study, we enrolled 43 non-diabetic young depressed males and adapted standard testing procedures to assess glucose metabolism during 4-week hospitalization. Before and after the 4-week antidepressant treatment, participants underwent oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance test (FSIGT). Insulin sensitivity (SI), glucose effectiveness (SG), acute insulin response, and disposition index (DI) were estimated using the minimal model method. The plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), and adiponectin were measured. The Hamilton depression rating scale (HAM-D) total scores were reduced significantly during the course of treatment. There were no significant changes in the parameters ofSI,SG, and DI. Compared to drug naïve status, the level of plasma IL-6 was significantly elevated (0.77to1.30 pg/ml;P=.001) after antidepressant therapy. However, the concentrations of CRP, TNF-α, and adiponectin showed no differences during the course of treatment. The results suggest that antidepressants may promote stimulatory effect on the IL-6 production in the early stage of antidepressant treatment.

GLUCOSE TOLERANCE AND INSULIN SECRETION IN HYPERTHYROIDISM

1977 ◽  
Vol 84 (3) ◽  
pp. 576-587 ◽  
Author(s):  
O. Ortved Andersen ◽  
Th. Friis ◽  
B. Ottesen
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Cell Mass ◽  
Insulin Response ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Glucose Response ◽  
Intravenous Glucose ◽  
Insulin Responses

ABSTRACT To evaluate the glucose tolerance and insulin secretion in hyperthyroidism patients were examined in the toxic state and after they had been made euthyroid. Fasting values: In 42 untreated patients the glucose- and insulin concentrations in serum were significantly elevated. In 24 treated patients the glucose concentrations became normal, while the insulin concentrations remained elevated. Oral-glucose-tolerance test: In 20 untreated patients the glucose- and insulin responses were significantly increased. In 8 treated patients the glucose response became normal, while the insulin response remained unchanged. Intravenous-glucose-tolerance test: In 28 untreated patients the K-values were significantly decreased and the insulin response increased. In 23 treated patients the K-values rose significantly, but the insulin response remained unchanged. Intravenous-tolbutamide test: In 41 untreated patients the glucose concentration decreased significantly compared with the controls, and the insulin responses were significantly increased. In 23 treated patients the glucose concentrations decreased even more, while the insulin response remained unchanged. The results indicate enhanced sensitivity or an increase in the mass of β-cells in hyperthyroidism. The glucose tolerance tests point to an increased peripheral insulin resistance. The normalized glucose tolerance and still enhanced insulin secretion during treatment support the assumption, that hyperthyroidism causes an increase in the β-cell mass.

scholarly journals Free triiodothyronine plasma concentrations are positively associated with insulin secretion in euthyroid individuals

2008 ◽  
Vol 158 (2) ◽  
pp. 217-221 ◽  
Author(s):  
Emilio Ortega ◽  
Juraj Koska ◽  
Nicola Pannacciulli ◽  
Joy C Bunt ◽  
Jonathan Krakoff
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Plasma Concentrations ◽  
Insulin Response ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Free Triiodothyronine ◽  
Intravenous Glucose ◽  
Fasting Plasma

BackgroundThyroid hormones (TH) may influence glucose metabolism. Hyperthyroid subjects have higher insulin secretion rates when compared with euthyroid individuals.ObjectiveTo evaluate the association between TH concentrations and insulin secretion in euthyroid, healthy Pima Indian adults (n=55, 29±7 years, females/males 36/19) with normal glucose tolerance (NGT) admitted to a Clinical Research Unit.MethodsTSH, free thyroxine (FT4), 3,5,3′-l-tri-iodothyronine (FT3), and fasting plasma insulin (FPI) concentrations were measured in fasting plasma samples, percentage of body fat (%BF) by dual energy x-ray absorptiometry (DXA), acute insulin response (AIR), and incremental area under the curve (AUC) of insulin in response to a 25 g intravenous glucose tolerance test (IVGTT) and 75 g oral glucose tolerance test (OGTT) respectively and insulin action (M) during an euglycemic clamp.ResultsFT3 concentrations were associated with FPI, AIR, and insulin AUC both before (r=0.33, P=0.01; r=0.29, P=0.03; and r=0.35, P=0.008 respectively) and after adjustment for age, sex, %BF, glucose (fasting concentrations or glucose AUC), and M (β=0.09, P=0.01; β=0.16, P=0.03; and β=0.24, P=0.0007 respectively). No associations were found for TSH or FT4.ConclusionFT3 was associated with several measurements of insulin secretion in euthyroid individuals with NGT. T3 concentrations may play a role in the regulation of insulin secretion.

scholarly journals Identification of insulin secretory defects and insulin resistance during oral glucose tolerance test in a cohort of cystic fibrosis patients

2011 ◽  
Vol 165 (1) ◽  
pp. 69-76 ◽  
Author(s):  
A Battezzati ◽  
A Mari ◽  
L Zazzeron ◽  
G Alicandro ◽  
L Claut ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Cell Function ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Β Cell ◽  
Β Cell Function

BackgroundCystic fibrosis (CF)-related diabetes is a leading complication of CF and is associated with pulmonary and nutritional deterioration, years before an evident hyperglycemia, possibly because of insulin deficiency and resistance.AimTo evaluate glucose tolerance, insulin secretion, and insulin sensitivity by a widely applicable method suitable for accurate and prospective measurements in a CF population.MethodsA total of 165 CF subjects (80 females) aged 17±5 years and 18 age- and sex-matched healthy controls (CON) received an oral glucose tolerance test with glucose, insulin and C-peptide determinations. Insulin sensitivity was defined on the basis of glucose and insulin concentrations using the oral glucose insulin sensitivity index, whereas β-cell function was determined on the basis of a model relating insulin secretion (C-peptide profile) to glucose concentration.ResultsFifteen percent of CF patients had glucose intolerance and 6% had diabetes without fasting hyperglycemia and 3% had diabetes with fasting hyperglycemia. β-cell function was reduced in CF patients compared with CON (70.0±4.1 vs 117.9±11.6 pmol/min per m2 per mM, P<0.001) and decreased significantly with age by −2.7 pmol/min per m2 per mM per year (confidence interval (CI) −4.5 to −0.82), i.e. almost 4% yearly. The early insulin secretion index was also reduced. Insulin sensitivity was similar to CON. CF patients who attained glucose tolerance comparable to CON had lower β-cell function and higher insulin sensitivity.ConclusionThe major alteration in insulin secretion and insulin sensitivity of CF patients is slowly declining β-cell function, consisting of delayed and reduced responsiveness to hyperglycemia, that in CF patients with normal glucose tolerance may be compensated by an increased insulin sensitivity.

scholarly journals First-phase insulin response (FPIR) to intravenous glucose tolerance test (IVGTT), insulin sensitivity and long-term follow-up in ?- transfusion-dependent thalassemia (TDT) normoglycemic patients with reduced insulin secretion to oral glucose tolerance t

2021 ◽  
Vol 13 (1) ◽  
pp. e2021021
Author(s):  
Vincenzo De Sanctis
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Tolerance Test ◽  
Insulin Response ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Intravenous Glucose

Summary. Objective: To  study the function of the endocrine pancreas in transfusion-dependent ?-thalassemia (?-TDT) patients with normal oral glucose tolerance test (OGTT) and hypoinsulinemia. Patients and methods: Seven ?-TDT patients  (mean age 22.4 ± 4.2 years) with normal glucose tolerance test (NGT) and poor insulin response (hypoinsulinemia) to OGTT,  not associated with ?-cell autoimmunity, were referred for a second opinion to an Italian Centre, part of the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescence Medicine (ICET-A). In this pilot study,  the first-phase insulin response (FPIR), expressed as the sum of 1 and  3 minutes insulin, of ?-TDT patients to intravenous glucose tolerance test (IVGTT), was tested. Moreover, the long-term natural history was followed prospectively using an annual OGTT, with the aim of detecting any abnormality of glucose metabolism. Results: The FPIR value  was between the 1st and 3rd percentile in two patients and between the 3rd and 10th percentile in  five. After 43 ± 26 months (range 11 - 80 months) of follow-up, 2 patients developed impaired glucose tolerance (IGT), 3 both IGT and impaired fasting glucose (IFG) and two overt diabetes mellitus (DM). Interestingly, the patients who developed DM had, at baseline the lowest value of insulinogenic index (IGI, 0.08 and 0.25), defined as the ratio of the increment of plasma insulin to plasma glucose during the first 30 minutes after OGTT. Moreover, a significant correlation was found between the IGI at baseline and at follow-up in the patients who developed IGT with or without IFG (R= 0.927; P: 0.023). A significant reduction of Matsuda insulin sensitivity index (ISIM) and Insulin Secretion-Sensitivity Index-2 (ISSI-2) was documented in the study cohort at diagnosis of IFG, IGT and DM. There was a significant inverse correlation between ISSI-2 and area under the curve of plasma glucose (AUC-PG). Conclusions: These data demonstrated, for the first time, a progressive deterioration in glucose homeostasis in ?-TDT subjects with NGT and hypoinsulinemia.  Thus, we consider that variations of insulin sensitivity could possibly have an impact on glucose tolerance in adult patients with TDT. Further investigations should focus on factors that might positively influence insulin sensitivity, including nutrition, drugs and physical activity.  

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