Éditeur(s) : HAL CCSD American Society for Biochemistry and Molecular Biology
Résumé : International audience
Chronic low grade inflammation is closely linked to obesity-associated insulin resistance. To examine how administration of the anti-inflammatory compound indomethacin, a general cyclooxygenase inhibitor, affected obesity development and insulin sensitivity, we fed obesity-prone male C57BL/6J mice a high fat/high sucrose (HF/HS) diet or a regular diet supplemented or not with indomethacin (±INDO) for 7 weeks. Development of obesity, insulin resistance, and glucose intolerance was monitored, and the effect of indomethacin on glucose-stimulated insulin secretion (GSIS) was measured in vivo and in vitro using MIN6 β-cells. We found that supplementation with indomethacin prevented HF/HS-induced obesity and diet-induced changes in systemic insulin sensitivity. Thus, HF/HS+INDO-fed mice remained insulin-sensitive. However, mice fed HF/HS+INDO exhibited pronounced glucose intolerance. Hepatic glucose output was significantly increased. Indomethacin had no effect on adipose tissue mass, glucose tolerance, or GSIS when included in a regular diet. Indomethacin administration to obese mice did not reduce adipose tissue mass, and the compensatory increase in GSIS observed in obese mice was not affected by treatment with indomethacin. We demonstrate that indomethacin did not inhibit GSIS per se, but activation of GPR40 in the presence of indomethacin inhibited glucose-dependent insulin secretion in MIN6 cells. We conclude that constitutive high hepatic glucose output combined with impaired GSIS in response to activation of GPR40-dependent signaling in the HF/HS+INDO-fed mice contributed to the impaired glucose clearance during a glucose challenge and that the resulting lower levels of plasma insulin prevented the obesogenic action of the HF/HS diet.
The journal of biological chemistry

hal-01063926
https://hal.archives-ouvertes.fr/hal-01063926
DOI : 10.1074/jbc.M113.525220

Éditeur(s) : HAL CCSD American Diabetes Association
Résumé : International audience
OBJECTIVE: To compare incidences and risk factors for diabetes using seven definitions, with combinations of pharmacological treatment, fasting plasma glucose (FPG) ≥7.0 mmol/L, and HbA(1c) ≥6.5%. RESEARCH DESIGN AND METHODS: Participants aged 30-65 years from the Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort were followed for 9 years. RESULTS: More men had incident diabetes as defined by FPG ≥7.0 mmol/L and/or treatment than by HbA(1c) ≥6.5% and/or treatment: 7.5% (140/1,867) and 5.3% (99/1,874), respectively (P < 0.009); for women incidences were similar: 3.2% (63/1,958) and 3.4% (66/1,954). Known risk factors predicted diabetes for almost all definitions. Among those with incident diabetes by FPG alone versus HbA(1c) alone, there were more men (78 vs. 35%), case patients were 8 years younger, and fewer were alcohol abstainers (12 vs. 35%) (all P < 0.005). A diabetes risk score discriminated well between those with and without incident diabetes for all definitions. CONCLUSIONS: In men, FPG definitions yielded more incident cases of diabetes than HbA(1c) definitions, in contrast with women. An FPG-derived risk score remained relevant for HbA(1c)-defined diabetes.
Diabetes Care

inserm-00739799
http://www.hal.inserm.fr/inserm-00739799
http://www.hal.inserm.fr/inserm-00739799/document
DOI : 10.2337/dc10-1581
PUBMED : 21346181

Éditeur(s) : HAL CCSD American Society for Biochemistry and Molecular Biology
Résumé : International audience
Chronic low grade inflammation is closely linked to obesity-associated insulin resistance. To examine how administration of the anti-inflammatory compound indomethacin, a general cyclooxygenase inhibitor, affected obesity development and insulin sensitivity, we fed obesity-prone male C57BL/6J mice a high fat/high sucrose (HF/HS) diet or a regular diet supplemented or not with indomethacin (±INDO) for 7 weeks. Development of obesity, insulin resistance, and glucose intolerance was monitored, and the effect of indomethacin on glucose-stimulated insulin secretion (GSIS) was measured in vivo and in vitro using MIN6 β-cells. We found that supplementation with indomethacin prevented HF/HS-induced obesity and diet-induced changes in systemic insulin sensitivity. Thus, HF/HS+INDO-fed mice remained insulin-sensitive. However, mice fed HF/HS+INDO exhibited pronounced glucose intolerance. Hepatic glucose output was significantly increased. Indomethacin had no effect on adipose tissue mass, glucose tolerance, or GSIS when included in a regular diet. Indomethacin administration to obese mice did not reduce adipose tissue mass, and the compensatory increase in GSIS observed in obese mice was not affected by treatment with indomethacin. We demonstrate that indomethacin did not inhibit GSIS per se, but activation of GPR40 in the presence of indomethacin inhibited glucose-dependent insulin secretion in MIN6 cells. We conclude that constitutive high hepatic glucose output combined with impaired GSIS in response to activation of GPR40-dependent signaling in the HF/HS+INDO-fed mice contributed to the impaired glucose clearance during a glucose challenge and that the resulting lower levels of plasma insulin prevented the obesogenic action of the HF/HS diet.
ISSN: 0021-9258

hal-01074835
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01074835
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01074835/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01074835/file/JBC-2013-525220v2-Kristiansen-POSTPRINT.pdf
DOI : 10.1074/jbc.M113.525220

Éditeur(s) : HAL CCSD
Résumé : International audience
AIM:We aimed to study the relationships between circulating 25-hydroxyvitamin D [25(OH)D], insulin resistance and leptin-to-adiponectin (L/A) ratio in Guadeloupean children and adolescents and to analyse the changes in 25(OH)D levels after a 1-year lifestyle intervention program.METHODS:25(OH)D concentrations were measured via a chemiluminescence assay. Cardiometabolic risk factors, homoeostasis model assessment of insulin resistance (HOMA-IR), and adipokines were measured. The lifestyle intervention included dietary counselling, regular physical activity.RESULTS:Among 117 girls and boys (11–15 years old, 31.6% obese), 40% had vitamin D deficiency (25(OH)D levels < 20 ng/mL). With linear regression models where 25(OH)D and HOMA-IR acted as independent variables and age, sex, BMI, L/A ratio as covariates, 25(OH)D was significantly associated with HOMA-IR alone (P = 0.036). HOMA-IR was also associated with BMI z-score ≥ 2, L/A ratio and an interaction term BMI z-score ≥ 2*L/A ratio (P < 0.001 for all). After one year, in 78 children/adolescent, mean serum 25(OH)D increased significantly from 21.4 ± 4.9 ng/mL at baseline to 23.2 ± 6.0 after 1 year; P = 0.003 whereas BMI z-score, HOMA-IR and L/A ratio decreased significantly (P = 0.003, P < 0.001 and P = 0.012; respectively).CONCLUSION:The association between 25(OH)D and HOMA-IR, independently of obesity and the high prevalence of vitamin D deficiency should be considered in order to prevent the later incidence of T2DM. A healthy lifestyle including non-sedentary and outdoor activities could be a way for improving vitamin D status.
Open Access Macedonian Journal of Medical Sciences

hal-01427889
http://hal.upmc.fr/hal-01427889
PUBMEDCENTRAL : PMC5175505

Éditeur(s) : HAL CCSD
Résumé : International audience
Introduction: Diabetes mellitus results from the loss of tolerance to insulin and alters glycemia and the glycogen content. Oxidative stress and inflammation are linked to theses alterations, especially with insulin-resistance. The therapy management of diabetes includes nutritional recommendations. Several nutrients are developed to improve glycemia, oxidative stress, inflammation and glycogen content. More interestingly, ?-GOS exhibits anti-inflammatory and insulin-sensitive effects in vitro (Efstathiou and Fathi 2010) and in vivo (Boucher et al. 2003). Thus, ?-GOS is a potential functional food for the treatment of diabetes. But, less is known about the in vivo effect of ?-GOS on inflammatory, glycoxidation markers and glycogen content in diabetes. In this context, the aim of this work was to study the effect of ?-GOS developed by Sojasun technologies (from fermented soy product) compared to a synthetic ?-GOS produced by Sigma on inflammatory, glycoxidation markers and glycogen content in a streptozotocin-induced diabetic rat model. Methods: Twenty-four male Wistar streptozotocin-diabetic rat (STZ) were divided into three group: control group, supplemented with natural ?-GOS (20 mg/kg/day) group and supplemented with synthetic ?-GOS (20 mg/kg/day). The supplementation protocol duration was 8 weeks. At the end of the protocol, blood and skeletal muscle (gastrocnemius) were obtained to measure glucose , insulin, fructosamine in plasma and N-(carboxymethyl)lysine, glycogen synthase activity and glycogen content, in muscle. Results-Discussion: Diabetes was confirmed with the measure of insuline and glucose levels. All the diabetic groups had significantly higher glucose and insuline levels compared to control healthy group (data not shown). Insuline level in plasma and storage of glycogen in muscle were increased only in both ?-GOS groups. Fructosamine, TNF?and glycogen synthase activity was also decreased in the two supplemented groups (synthetic ?-GOS and natural ?-GOS). CML remained unchanged in all groups. Natural ?-OGT and synthetic ?-OGT only differed on muscular glucose level: only natural ?-OGT induced a significant decrease in muscular glucose. To conclude, our results suggest that ?-GOS alters positively glucose level, increases the glycogen content in diabetique population, improves glycemic control in the long term and decreases the inflammatory effects in streptozotocin-diabetic rat . Keywords: ?-GOS, inflammatory and glycoxidation markers, diabetes. Acknowledgment : Brittany region References Efstathiou, T. and D. Fathi. Sojasun Technologies. 2010 Boucher J et al. J Physiol Biochem. 59(3):169-73, 2003
5e congrès international de "Nutrition, Oxygen Biology and Medicine", Paris 5-7 juin 2013
Paris, France

hal-01159375
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01159375

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: Overweight in Guadeloupe is a public health matter affecting children and adults. In the present study we evaluated the metabolic profile, including serum ghrelin, leptin and adiponectin levels, in normal weight, overweight and obese school children and we analyzed the potential changes in anthropometric and metabolic risk factors after a 1-year lifestyle intervention program. Methods: Parameters were assessed at baseline and at 1 year. Three groups (G) were defined according the International Obesity Task Force reference values, G1: normal weight / G2: overweight / G3: obese. The lifestyle intervention included dietary counseling, regular physical activity and family support. Results: A total of 120 children (G1: n = 44, G2: n = 39, G3: n = 37), aged 11– 15 years and 59 % girls were enrolled. Obese children showed significant lower HDL-C, adiponectin and ghrelin concentrations, higher triglycerides, fasting blood glucose, insulin and leptin levels and also higher frequencies of abdominal obesity (G1: 2.3 %, G2: 28.2 %, G3: 73 %) and insulin resistance (GI: 39 %, G2: 72 %, G3: 89 %) than the other groups. In the overall sample, the linear regressions exploring the associations of ghrelin, adiponectin and leptin with age, gender, BMI z-score, HOMA-IR and tanner stage as independent variables showed strong associations of leptin levels with weight status and insulin resistance at baseline. The models accounted for 58 % of variability in leptin levels compared with 26 and 15 % for adiponectin and ghrelin levels respectively. In 83 children who completed the program, significant decreases in BMI z-score in overweight and obese children were noted. Leptin levels decreased significantly only in the obese group whereas adiponectin concentrations increased significantly in the three groups, In obese children, a significant correlation was found between changes in BMI Z-score, and changes in leptin levels (r = 0.39; P = 0.049) but not with changes in adiponectin levels. Conclusions: Abdominal obesity and insulin resistance were highly prevalent in obese children highlighting their risk of metabolic complications in adulthood. A 1-year long lifestyle intervention was associated with improvement in BMI z-score and metabolic parameters.
ISSN: 1743-7075

Droits : http://creativecommons.org/licenses/by/
hal-01231394
http://hal.upmc.fr/hal-01231394
http://hal.upmc.fr/hal-01231394/document
http://hal.upmc.fr/hal-01231394/file/art_10.1186_s12986-015-0039-9.pdf
DOI : 10.1186/s12986-015-0039-9

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
OBJECTIVE: To evaluate the incidence and determinants of diabetes in a cohort of HIV-infected adults initiated with combination antiretroviral treatment (cART) in 1997-1999 and followed up to 2009. DESIGN: Prospective study of 1046 patients at 47 French clinical sites. METHODS: Potential determinants of diabetes occurrence, defined by confirmed increased glycemia and/or initiation of antidiabetic treatment, were assessed by a proportional hazards model, including time-updated metabolic parameters and ART exposure. RESULTS: Among the cohort, representing 7846 person-years of follow-up (PYFU), 54% received indinavir, 75% stavudine and 52% didanosine. Overall, 111 patients developed diabetes, with an incidence of 14.1/1000 PYFU (14.6 in men, 12.6 in women). Incidence peaked in 1999-2000 (23.2/1000 PYFU) and decreased thereafter. The incidence of diabetes was associated [adjusted hazard ratio (aHR), all P<0.02] with older age (hazard ratio = 2.13 when 40-49 years, hazard ratio = 3.63 when ≥50 years), overweight (hazard ratio = 1.91 for a BMI 25-29 kg/m(2), hazard ratio = 2.85 >30 kg/m(2)), waist-to-hip ratio (hazard ratio = 3.87 for ≥0.97 male/0.92 female), time-updated lipoatrophy (hazard ratio = 2.14) and short-term exposure to indinavir (0-1 year: hazard ratio = 2.53), stavudine (0-1 year: hazard ratio = 2.56, 1-2 years: hazard ratio = 2.65) or didanosine (2-3 years: hazard ratio = 3.16). Occurrence of diabetes was not associated with HIV-related markers, hepatitis C, hypertension or family history of diabetes. Insulin resistance was predictive for incident diabetes. CONCLUSIONS: In this nationwide cohort, followed for 10 years after cART initiation, diabetes incidence peaked in 1990-2000, was markedly higher than that reported for European uninfected or other HIV-infected populations (4-6/1000 PYFU) and linked with age and adiposity. Adiposity and glycemic markers should be monitored in aging HIV-infected patients.
ISSN: 0269-9370

hal-00875222
https://hal.archives-ouvertes.fr/hal-00875222
DOI : 10.1097/QAD.0b013e32834e8776
PUBMED : 22089377