A5000959795- Birth, Development, and Health
- Cardiovascular Function and Risk Factors
- Pregnancy and preeclampsia studies
- Gestational Diabetes Research and Management
- Pancreatic function and diabetes
- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Diabetes Treatment and Management
- Neonatal Respiratory Health Research
- Growth Hormone and Insulin-like Growth Factors
- Regulation of Appetite and Obesity
- Cardiomyopathy and Myosin Studies
- Cardiac Fibrosis and Remodeling
- Glycosylation and Glycoproteins Research
- Reproductive Physiology in Livestock
- S100 Proteins and Annexins
- Diet, Metabolism, and Disease
- Adipokines, Inflammation, and Metabolic Diseases
- MicroRNA in disease regulation
- Cardiovascular Disease and Adiposity
- Endoplasmic Reticulum Stress and Disease
- Galectins and Cancer Biology
- Advanced Glycation End Products research
- Mitochondrial Function and Pathology
- Diabetes Management and Research
Monash University
2006-2025
Baker Heart and Diabetes Institute
2015-2023
University of Cambridge
2015-2023
The University of Melbourne
2016-2021
Monash Health
2021
The University of Adelaide
2007-2017
Max Planck Institute for Heart and Lung Research
2017
University of Turin
2017
Goethe University Frankfurt
2017
Robinson Memorial Hospital
2015
Obesity is highly prevalent, and its incidence increasing. The previous study showing a major effect of paternal obesity on metabolic health offspring confounded by comorbidity with diabetes. Therefore, we investigated the diet-induced obesity, in absence diabetes, two resultant generations molecular profiles testes sperm. Founder (F0) male C57BL6 mice were fed either high-fat diet (HFD) or control (CD); n = 10/diet for period 10 wk. Testis expression mRNA/microRNAs was analyzed microarray...
Abstract Aims The glucose-driven enzymatic modification of myocardial proteins by the sugar moiety, β-N-acetylglucosamine (O-GlcNAc), is increased in pre-clinical models diabetes, implicating protein O-GlcNAc diabetes-induced heart failure. Our aim was to specifically examine cardiac manipulation two regulatory enzymes this process on phenotype, presence and absence utilising cardiac-targeted recombinant-adeno-associated viral-vector-6 (rAAV6)-mediated gene delivery. Methods results In human...
Most children who are short or light at birth due to intrauterine growth restriction (IUGR) exhibit accelerated in infancy, termed “catch-up” growth, which together with IUGR, predicts increased risk of type 2 diabetes and obesity later life. Placental (PR) sheep reduces size birth, also causes catch-up adiposity 6 wk age. The physiological mechanisms responsible for after IUGR its links these adverse sequelae unknown. Because insulin is a major anabolic hormone infancy actions commonly...
Intrauterine growth restriction (IUGR) is associated with accelerated after birth. Together, IUGR and birth predict reduced lean tissue mass increased obesity in later life. Although placental insufficiency a major cause of IUGR, whether it alters adiposity early postnatal life not known. We hypothesized that (PR) the sheep would reduce size at increase rate, fat mass, feeding activity young lamb. PR survival rate birth, soft tissues to greater extent than skeletal relative sparing head...
Prenatal and early postnatal life experiences, reflected by size at birth catch-up growth, contribute to the risk of developing metabolic syndrome in adulthood, but their relative importance is unclear. Therefore, we determined effects restricted placental fetal growth on components young adult sheep relationships latter growth. Fasting plasma metabolites, glucose tolerance (by intravenous test, IVGTT), insulin secretion sensitivity, resting blood pressure were measured 22 control 20...
An adverse intrauterine environment increases the risk of developing various adult-onset diseases, whose nature varies with timing exposure. Maternal undernutrition in humans can increase adiposity, and coronary heart disease impaired glucose tolerance adult life, which may be partly mediated by maternal or fetal endocrine stress responses. In sheep, dexamethasone early pregnancy impairs cardiovascular function, but not homeostasis female offspring. However, male offspring are often more...
Intrauterine growth restriction and accelerated postnatal predict increased risk of diabetes. Uteroplacental insufficiency in the rat restricts fetal but also impairs mammary development growth. We used cross fostering to compare influence prenatal nutritional restraint on adult glucose tolerance, insulin secretion, sensitivity, hypothalamic neuropeptide Y content Wistar Kyoto rats at 6 months age. Bilateral uterine vessel ligation (restricted) induce uteroplacental or sham surgery (control)...
Poor growth before birth increases the risk of non-insulin-dependent diabetes mellitus (NIDDM) and impairs insulin secretion relative to sensitivity. We investigated effects intrauterine restriction in sheep on secretion, β-cell mass, function from young adulthood its molecular basis. Pancreas was collected control placentally restricted as fetuses (d 143 gestation), lambs (aged 42 d), adults 556 following independent measures vivo β-Cells islets were counted after immunohistochemical...
Phosphoinositide 3-kinase [PI3K (p110α)] is able to negatively regulate the diabetes-induced increase in NADPH oxidase heart. Patients affected by diabetes exhibit significant cardiovascular morbidity and mortality, at least part due a cardiomyopathy characterized oxidative stress left ventricular (LV) dysfunction. Thus, PI3K (p110α) may represent novel approach protect heart from cardiac In present study, we investigated therapeutic potential of delayed intervention with cardiac-targeted...
Abstract Diabetic cardiomyopathy is a distinct pathology characterized by early emergence of diastolic dysfunction. Increased cardiovascular risk associated with diabetes more marked for women, but an understanding the role dysfunction in female susceptibility to diabetic lacking. To investigate sex-specific relationship between systemic status and vivo occurrence dysfunction, was induced male mice streptozotocin (5x daily i.p. 55 mg/kg). Echocardiography performed at 7 weeks post-diabetes...
The incidence of diabetes and its association with increased cardiovascular disease risk represents a major health issue worldwide. Diabetes-induced hyperglycemia is implicated as central driver responses in the diabetic heart such cardiomyocyte hypertrophy, fibrosis, oxidative stress, termed cardiomyopathy. onset these setting has not been studied to date. This study aimed determine time course development cardiomyopathy model type 1 (T1D) vivo. Diabetes was induced 6-week-old male FVB/N...
Numerous epidemiological studies have related an increased risk of adult-onset cardiovascular and metabolic disease to adverse intra-uterine environment at critical periods. We shown that fetal sheep exposed dexamethasone for only 2 days 27 gestation (term ≈ 150 days) became hypertensive adults, whereas those 64 remained normotensive, as did controls. In the same sheep, now nearly 5 years old, we performed glucose tolerance tests hyperinsulinaemic euglycaemic clamps study insulin sensitivity...
Rationale: Human cardiac mesenchymal cells (CMSCs) are a therapeutically relevant primary cell population. Diabetes mellitus compromises CMSC function as consequence of metabolic alterations and incorporation stable epigenetic changes. Objective: To investigate the role α-ketoglutarate (αKG) in epimetabolic control DNA demethylation CMSCs. Methods Results: Quantitative global analysis, methylated hydroxymethylated sequencing, gene-specific GC methylation detection revealed an accumulation...
Key points Fetal nutrient supply is dependent, in part, upon the transport capacity and metabolism of placenta. The stress hormone, cortisol, alters adult fetus but it not known whether cortisol pregnant mother affects In this study, when concentrations were raised sheep by infusion, proportionately more glucose taken up uterus was consumed uteroplacental tissues while less transferred to fetus, despite an increased placental capacity. Concomitantly, produced lactate at a greater rate....
Diabetic cardiomyopathy is a distinct form of heart disease that represents major cause death and disability in diabetic patients, particularly, the more prevalent type 2 diabetes patient population. In current study, we investigated whether administration recombinant adeno-associated viral vectors carrying constitutively active phosphoinositide 3-kinase (PI3K)(p110α) construct (rAAV6-caPI3K) at clinically relevant time point attenuates preclinical (T2D) model. T2D was induced by combination...
Restricted growth before birth is associated with impaired insulin secretion but initially enhanced sensitivity in early postnatal life, which then progresses to resistance and glucose homeostasis by adulthood. This suggests that prenatal restraint impairs secretion, increases sensitivity, birth. Poor placental function are major causes of restricted fetal humans. We have therefore investigated the effects on plasma glucose, alpha-amino nitrogen concentrations glucose- arginine-stimulated...
Poor growth before birth is associated with impaired insulin sensitivity later in life, increasing the risk of type 2 diabetes. The tissue sites at which resistance first develops after intrauterine restriction (IUGR), and its molecular basis, are unclear. We have therefore characterized effects placental (PR), a major cause IUGR, on whole-body expression determinants signaling glucose uptake skeletal muscle liver young lambs. Whole-body was measured 30 d by hyperinsulinaemic euglycaemic...
This study was designed to compare glucose, lipids, and C-reactive protein (CRP) in women with gestational diabetes mellitus treated metformin or insulin cord plasma of their offspring examine how these markers relate infant size at birth.
Endogenous anti-inflammatory annexin-A1 (ANX-A1) plays an important role in preserving left ventricular (LV) viability and function after ischaemic insults vitro, but its long-term cardioprotective actions vivo are largely unknown. We tested the hypothesis that ANX-A1-deficiency exaggerates inflammation, haematopoietic stem progenitor cell (HSPC) activity LV remodelling response to myocardial ischaemia vivo. Adult ANX - A1 -/- mice subjected coronary artery occlusion exhibited increased...