A Model of Insulin Resistance in Mice, Born to Diabetic Pregnancy, Is Associated with Alterations of Transcription-Related Genes in Pancreas and Epididymal Adipose Tissue

Objective. This study is conducted on a model of insulin-resistant (IR) mice born to dams which were rendered diabetic by the administration of streptozotocin. Methods. Adult IR and control offspring were selected and we determined the mRNA expression of transcription factors known to modulate pancreatic and adipose tissue activities and inflammation. Results. We observed that serum insulin increased, and the mRNA of insulin gene transcription factors, Pdx-1, Nkx6.1 and Maf-A, were upregulated in IR mice pancreas. Besides, their pancreatic functional capacity seemed to be exhausted as evidenced by low expression of pancreatic Glut2 and glucokinase mRNA. Though IR offspring exhibited reduced epididymal adipose tissue, their adipocytes seemed to be differentiated into macrophage-like cells, as they exhibited upregulated CD14 and CD68 antigens, generally expressed by macrophages. However, there was no peripheral macrophages infiltration into epididymal adipose tissue, as the expression of F4/80, a true macrophage marker, was undetectable. Furthermore, the expression of IL-6, TNF-α and TLR-2, key players of insulin resistance, was upregulated in the adipose tissue of IR offspring. Conclusion. Insulin resistant state in mice, born to diabetic pregnancy, alters the expression of function-related genes in pancreas and epididymal adipose tissue and these offspring are prone to develop metabolic syndrome

Typologie Des Gîtes Larvaires Et Résistance Des Vecteurs Du Paludisme A La Deltaméthrine Dans les Milieux Urbain Et Rural Du Département De l’Atlantique Au Sud Du Bénin: Données Préliminaires

La lutte antilarvaire récemment recommandée par l’OMS, requiert une connaissance approfondie de la distribution et de la typologie des gîtes larvaires des vecteurs du paludisme. L’objectif de cette étude est d’identifier les différents gîtes larvaires des anophèles et leur mécanisme de résistance à la deltaméthrine. Des prospections larvaires ont été effectuées en 2017 durant les saisons pluvieuses et sèches dans trois communes au sud du Bénin. Les moustiques issus de l’émergence des larves ont été soumis à la deltaméthrine et au bendiocarb selon le protocole de l’OMS. L’identification moléculaire des anophèles et le génotypage de la mutation Kdr ont été réalisés par PCR et l’expression des oxydases, des estérases α et β, et des GST ont été mesurées. Les prospections larvaires ont permis de répertorier 37 gîtes larvaires regroupés en 13 types. La majorité des gîtes étaient anthropiques. La densité larvaire variait d’un type de gîtes à l’autre. An. coluzzii et An. gambiae étaient les deux vecteurs du paludisme vivant en sympatrie dans lestroissites d’étude. Ils sont fortement résistants à la deltaméthrine avec la présence de la mutation kdr à des fréquences très élevées et une augmentation des activités des estérases dans les populations d’anophèles collectés à Zè et des GST à Abomey-Calavi et Allada. La prolifération des vecteurs du paludisme serait imputable à l’insalubrité de l’environnement immédiat et aux activités anthropiques qui créent et assurent le maintien des gîtes larvaires. Ces données pourraient servir au renforcement des stratégies de lutte contre le paludisme déjà en cours. Anopheles larval control, recently recommended by WHO, requires a deep knowledge of the distribution and typology of larval breeding sites. The objective of this study is to identify the different larval habitats colonized by Anopheles and their insecticide resistance mechanism. Larval surveys were carried out in three Districts in south of Benin in 2017, during the rainy and dry seasons. Mosquitoes breeding sites have been characterized and mapped. Mosquitoes from the emergence of larvae were tested to deltamethrin and bendiocarb according to the WHO protocol. The molecular identification of anopheles and the genotyping of the kdr mutation were performed by PCR and the expression of oxidases, esterases, and GSTs was measured. Larval surveys have identified 37 breeding sites categorized into 13 types. Most of the larval habitats were anthropogenics. An. coluzzii and An. gambiae were the two malaria vectors found in sympatric in the three study sites. These two vectors were highly resistant to deltamethrin with the presence of the kdr L1014F mutation at very high frequencies and an increase in esterase activities in anopheline populations collected in Zè and GST in Abomey-Calavi and Allada. The proliferation of malaria vectors is attributable to the unhealthy environment and human activities that create and maintain mosquito breeding. This study highlighted diversity in the type of breeding site of An. gambiae s.s in the Atlantic Department, suggesting the adaptation of this species in its environment. These results could be used to develop an antilarval control strategy in Abomey-Calavi, Zè and in Allada

Multiple insecticide resistance in an infected population of the malaria vector Anopheles funestus in Benin.

BACKGROUND Knowledge on the spread and distribution of insecticide resistance in major malaria vectors such as Anopheles funestus is key to implement successful resistance management strategies across Africa. Here, by assessing the susceptibility status of an inland population of An. funestus Giles (Kpome) and investigating molecular basis of resistance, we show that multiple resistance and consistent plasmodium infection rate are present in Anopheles funestus populations from Kpome. METHODS The insecticide susceptibility level of collected Anopheles funestus was assessed. Synergist (PBO) was used to screen resistance mechanisms. The TaqMan technique was used for genotyping of insecticide resistant alleles and detecting plasmodium infection levels. The nested PCR was used to further assess the plasmodium infection rate. RESULTS The TaqMan analysis of plasmodial infections revealed an infection rate (18.2 %) of An. funestus in this locality. The WHO bioassays revealed a multiple phenotypic resistance profile for An. funestus in Kpome. This population is highly resistant to pyrethroids (permethrin and deltamethrin), organochlorines (DDT), and carbamates (bendiocarb). A reduced susceptibility was observed with dieldrin. Mortalities did not vary after pre-exposure to PBO for DDT indicating that cytochrome P450s play little role in DDT resistance in Kpome. In contrast, we noticed, a significant increase in mortalities when PBO was combined to permethrin suggesting the direct involvement of P450s in pyrethroid resistance. A high frequency of the L119F-GSTe2 DDT resistance marker was observed in the wild DDT resistant population (9 %RS and 91 %RR) whereas the A296S mutation was detected at a low frequency (1 %RS and 99 %SS). CONCLUSION The presence of multiple resistance in An. funestus populations in the inland locality of Kpome is established in this study as recently documented in the costal locality of Pahou. Data from both localities suggest that resistance could be widespread in Benin and this highlights the need for further studies to assess the geographical distribution of insecticide resistance across Benin and neighboring countries as well as a more comprehensive analysis of the resistance mechanisms involved

Investigation of DDT resistance mechanisms in Anopheles funestus populations from northern and southern Benin reveals a key role of the GSTe2 gene

Background: Understanding the molecular basis of insecticide resistance in mosquito, such as Anopheles funestus is an important step in developing strategies to mitigate the resistance problem. This study aims to assess the role of the GSTe2 gene in DDT resistance and determine the genetic diversity of this gene in Anopheles funestus species. Methods: Gene expression analysis was performed using microarrays and PCR while the potential mutation associated with resistance was determined using sequencing. Results: Low expression level of GSTe2 gene was recorded in Burkina-Faso samples with a fold change of 3.3 while high expression (FC 35.6) was recorded in southern Benin in Pahou (FC 35.6) and Kpome (FC 13.3). The sequencing of GSTe2 gene in six localities showed that L119F-GSTe2 mutation is almost getting fixed in highly DDT-resistant Benin Pahou, Kpome, Doukonta and Nigeria (Akaka Remo) mosquitoes with a low mutation rate observed in Tanongou (Benin) and Burkina-Faso mosquitoes. Conclusion: This study shows the key role of the GSTe2 gene in DDT resistant Anopheles funestus in Benin. Polymorphism analysis of this gene across Benin revealed possible barriers to gene flow which could impact the design and implementation of resistance management strategies in the country

Modulation of immune cells and Th1/Th2 cytokines in insulin-treated type 2 diabetes mellitus.

Background: The role of the immune system in insulin resistance associated with type 2 diabetes has been suggested. Objectives: We assessed the profile of Th1/Th2 cytokines along with the frequencies of immune cells in insulin-treated type 2 diabetic patients (T2DP). Methods: 45 T2D patients and 43 age-matched healthy subjects were selected. Serum concentrations of T-helper type 1 (Th1) and Th2 cytokines and the frequencies of innate and adaptive immunity cells were assessed. Results: T2DP were hyperglycemic and showed high level of insulin, normal levels of triglycerides and total-cholesterol and without any change in HDL-cholesterol.Compared to healthy subjects, T2DP exhibited significant decreased frequencies of neutrophils, without any change in monocytes, eosinophils and natural killer cells. The percentages of total lymphocytes (CD3+) and CD8+-T-cells decreased whereas those of regulatory T-cells increased without any change in CD4+ T-cells in T2DP. Interestingly, the frequencies of effector CD4+-T and B-cells increased in T2DP. Serum concentrations of IL-2, IFN-\u3b3 and IL-4 decreased while IL-10 significantly enhanced in T2DP, suggesting a differentiation of CD4+T helper cells towards IL-10-producing- Teff-cells in these patients. Conclusion: Insulin-treated type 2 diabetes is associated with anti-inflammatory profile consistent with differentiation of CD4+-Th-cells towards IL-10-producing-Teff-cells, concomitant with increased frequencies of Treg and B-cells, and this may probably offer prevention against certain infections or autoimmune/inflammatory diseases

Growth factor concentrations and their placental mRNA expression are modulated in gestational diabetes mellitus: possible interactions with macrosomia

<p>Abstract</p> <p>Background</p> <p>Gestational diabetes mellitus (GDM) is a form of diabetes that occurs during pregnancy. GDM is a well known risk factor for foetal overgrowth, termed macrosomia which is influenced by maternal hypergycemia and endocrine status through placental circulation. The study was undertaken to investigate the implication of growth factors and their receptors in GDM and macrosomia, and to discuss the role of the materno-foeto-placental axis in the <it>in-utero </it>regulation of foetal growth.</p> <p>Methods</p> <p>30 women with GDM and their 30 macrosomic babies (4.75 ± 0.15 kg), and 30 healthy age-matched pregnant women and their 30 newborns (3.50 ± 0.10 kg) were recruited in the present study. Serum concentrations of GH and growth factors, <it>i.e</it>., IGF-I, IGF-BP3, FGF-2, EGF and PDGF-B were determined by ELISA. The expression of mRNA encoding for GH, IGF-I, IGF-BP3, FGF-2, PDGF-B and EGF, and their receptors, <it>i.e</it>., GHR, IGF-IR, FGF-2R, EGFR and PDGFR-β were quantified by using RT-qPCR.</p> <p>Results</p> <p>The serum concentrations of IGF-I, IGF-BP3, EGF, FGF-2 and PDGF-B were higher in GDM women and their macrosomic babies as compared to their respective controls. The placental mRNA expression of the growth factors was either upregulated (FGF-2 or PDGF-B) or remained unaltered (IGF-I and EGF) in the placenta of GDM women. The mRNA expression of three growth factor receptors, <it>i.e</it>., IGF-IR, EGFR and PDGFR-β, was upregulated in the placenta of GDM women. Interestingly, serum concentrations of GH were downregulated in the GDM women and their macrosomic offspring. Besides, the expression of mRNAs encoding for GHR was higher, but that encoding for GH was lower, in the placenta of GDM women than control women.</p> <p>Conclusions</p> <p>Our results demonstrate that growth factors might be implicated in GDM and, in part, in the pathology of macrosomia via materno-foeto-placental axis.</p

Maternal Diabetes in Pregnancy: Early and Long-Term Outcomes on the Offspring and the Concept of “Metabolic Memory”

The adverse outcomes on the offspring from maternal diabetes in pregnancy are substantially documented. In this paper, we report main knowledge on impacts of maternal diabetes on early and long-term health of the offspring, with specific comments on maternal obesity. The main adverse outcome on progenies from pregnancy complicated with maternal diabetes appears to be macrosomia, as it is commonly known that intrauterine exposure to hyperglycemia increases the risk and programs the offspring to develop diabetes and/or obesity at adulthood. This “fetal programming”, due to intrauterine diabetic milieu, is termed as “metabolic memory”. In gestational diabetes as well as in macrosomia, the complications include metabolic abnormalities, degraded antioxidant status, disrupted immune system and potential metabolic syndrome in adult offspring. Furthermore, there is evidence that maternal obesity may also increase the risk of obesity and diabetes in offspring. However, women with GDM possibly exhibit greater macrosomia than obese women. Obesity and diabetes in pregnancy have independent and additive effects on obstetric complications, and both require proper management. Management of gestational diabetes mellitus and maternal obesity is essential for maternal and offspring's good health. Increasing physical activity, preventing gestational weight gain, and having some qualitative nutritional habits may be beneficial during both the pregnancy and offspring's future life

Physiopathologie du diabète et de l'obésité (modulation nutritionnelle par le manioc du Bénin et les acides gras poly-insaturés de la famille n-3)

L étiologie et la physiopathologie du diabète et de l obésité sont aussi diverses que complexes. Bien que la prévalence du diabète lié à la malnutrition est en recul, celle du diabète de type 1, de type 2, du diabète gestationnel et du diabète lié à l alcool est en progression. Notre étude a montré, quelle que soit leur étiologie, que le diabète et l obésité sont liés à une altération du statut antioxydant et de la perturbation du métabolisme lipidique et du statut immunitaire. Si la consommation du manioc semble devoir être déconseillée chez le diabétique, car elle contribue à aggraver les complications liées à sa maladie, elle devrait intervenir chez les non diabétiques dans un contexte d alimentation équilibrée avec un apport suffisant en protéine. En effet, une alimentation adéquatement enrichie en huile de poissons (riche en AGPI n-3) présente des effets bénéfiques, chez les diabétiques et leurs progénitures macrosomiques et obèses, en améliorant leurs statut immunitaire et antioxydant et en corrigeant leur hyperlipidémie. PPARa, l un des récepteurs des AGPI n-3 et stimulateur du catabolisme des lipides et de l immunosuppression, constituerait une cible potentielle dans le traitement de l hyperlipidémie et de l état inflammatoire qui caractérisent le diabète et l obésité.The etiology and the physiopathology of diabetes and obesity are comprised of various and complex phenomena. Although the prevalence of malnutrition modulated-diabetes mellitus is decreased, those of type 1, type 2, gestational diabetes mellitus and alcohol related-diabetes mellitus are increased. Our study has demonstrated that, irrespective to their etiology, diabetes and obesity are related to the alteration of the antioxidant status, lipid metabolism and immune status. Feeding cassava should not be recommended for diabetic patients as it aggravates the diabetic complications. Cassava may be consumed by non-diabetic subjects with sufficient protein content. Indeed, fish oil-enriched diet presents beneficial effects in diabetic animals and their macrosomic/obese offspring, as it improves antioxidant and immune status and corrects the hyperlipidaemia. As PPARa being activated by n-3 polyunsaturated fatty acids (PUFA), and immunosuppressive and lipid catabolism activator, it may constitute a potential target molecule in the treatment of hyperlipidaemia and inflammatory state which characterize diabetes and obesity.DIJON-BU Médecine Pharmacie (212312103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF