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brain insulin resistance

Vishal Kothari, Yuwen Luo, Talia Tornabene, Ann Marie O'Neill, Michael W Greene, Geetha Thangiah, Jeganathan Ramesh Babu
High fat diet-induced obesity is associated with insulin resistance (IR) and other chronic, diet related illnesses, including dementia. Alzheimer disease is the most common form of dementia, and is characterized by the presence of amyloid plaques and neurofibrillary tangles in brain. This study was designed to determine whether diet-induced changes in peripheral insulin sensitivity could contribute to alterations in brain insulin signaling and cognitive functions. Four week old, male C57BL/6NHsd mice were randomly assigned a high fat diet (40% energy from fat) with 42g/L liquid sugar (HFS) added to the drinking water or a normal chow diet (12% energy from fat) for 14weeks...
October 19, 2016: Biochimica et Biophysica Acta
Vanessa Di Cataldo, Alain Géloën, Jean-Baptiste Langlois, Fabien Chauveau, Benoît Thézé, Violaine Hubert, Marlène Wiart, Erica N Chirico, Jennifer Rieusset, Hubert Vidal, Vincent Pialoux, Emmanuelle Canet-Soulas
Aim: Advanced atherosclerosis increases inflammation and stroke risk in the cerebral vasculature. Exercise is known to improve cardio-metabolic profiles when associated with a caloric restriction, but it remains debated whether it is still beneficial without the dietary control. The aim of this study was to determine both the peripheral and central effects of exercise training combined with a cholesterol-rich diet given ad libitum in old ApoE(-/-) mice. Methods: Forty-five-weeks old obese ApoE(-/-) mice fed with a high cholesterol diet ad libitum were divided into Exercise-trained (EX; running wheel free access) and Sedentary (SED) groups...
2016: Frontiers in Physiology
FangFang, Hongyan Li, Tingting Qin, Min Li, Shiping Ma
The impaired insulin signaling has been recognized as a common pathogenetic mechanism between diabetes and Alzheimer's disease (AD). In the progression of AD, brain is characterized by defective insulin receptor substrate-1 (IRS-1) and increased oxidative stress. Thymol, a monoterpene phenol isolated from medicinal herbs, has exhibited robust neuroprotective effects. The present study was designed to investigate the protective effect of thymol on HFD-induced cognitive deficits, and explore the possible mechanisms...
October 20, 2016: Metabolic Brain Disease
Shokei Kim-Mitsuyama
There is accumulating evidence that RAS inhibitors not only reduce blood pressure, but also exert pleiotropic effects, including a renoprotective effect, amelioration of insulin resistance, reduction in onset of diabetes, and suppression of cardiovascular remodelling,. However, the definite benefit of RAS inhibition in treatment of hypertension with CKD or DM is not conclusive. We previously performed the OlmeSartan and Calcium Antagonists Randomized (OSCAR) study comparing the preventive effect of high-dose ARB therapy versus ARB plus CCB combination therapy on cardiovascular morbidity and mortality in 1164 Japanese elderly hypertensive patients with baseline type 2 diabetes and/or CVD (Am J Med (2012))...
September 2016: Journal of Hypertension
Jie Zhang, Alan R Light, Charles L Hoppel, Caitlin Campbell, Carol J Chandler, Dustin J Burnett, Elaine C Souza, Gretchen A Casazza, Ronald W Hughen, Nancy L Keim, John W Newman, Gary R Hunter, Jose R Fernandez, W Timothy Garvey, Mary-Ellen Harper, Oliver Fiehn, Sean H Adams
With insulin-resistance or type 2 diabetes mellitus, mismatches between mitochondrial fatty acid fuel delivery and oxidative phosphorylation/tricarboxylic acid cycle activity may contribute to inordinate accumulation of short- or medium-chain acylcarnitine fatty acid derivatives (markers of incomplete long-chain fatty acid oxidation [FAO]). We reasoned that incomplete FAO in muscle would be ameliorated concurrent with improved insulin sensitivity and fitness following a ∼14 wk training and weight loss intervention in obese, sedentary, insulin-resistant women...
October 12, 2016: Experimental Physiology
O S Levin, E E Vasenina
Amyloid hypothesis of Alzheimer's disease (AD) has been long the primary one. During the 25-year history the concept has been dramatically changed. Accumulation of β-amyloid is associated not only with the disruption of its synthesis (as it seemed after the discovery of genetic mechanisms of some familial cases of AD) but rather with the disruption of its clearance and elimination from the brain tissue via the microcirculatory system. It has been recognized that soluble oligomers of β-amyloid, but not senile plaques that consisted of insoluble conjugates described by A...
2016: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
Antonella Tramutola, Andrea Arena, Chiara Cini, D Allan Butterfield, Eugenio Barone
Clinical studies suggest a link between peripheral insulin resistance and cognitive dysfunction. Post-mortem analyses of Alzheimer disease (AD) subjects revealed insulin resistance in the brain, suggesting a role of this condition in cognitive deficits observed in AD. In this review, we focus on the glucagon-like peptide-1 (GLP-1) signaling pathway, whose role in the brain is collecting increasing attention because of its association with insulin signaling activation. Areas covered: The role of GLP-1-mediated effects in the brain and how they are affected along the progression of AD pathology is discussed...
October 7, 2016: Expert Review of Neurotherapeutics
Ying Cui, Xia Liang, Hong Gu, Yuzheng Hu, Zhen Zhao, Xiang-Yu Yang, Cheng Qian, Yihong Yang, Gao-Jun Teng
To explore the effect of T2DM on cerebral perfusion, and the relationship between cerebral perfusion changes and cognitive impairment as well as diabetic variables, by using a whole-brain arterial spin-labeling (ASL) MRI technique. This prospective study was approved by the local institutional review board and was performed between November 2012 and October 2013. All subjects provided informed consent. Forty T2DM patients and 41 age-, sex- and education-matched healthy controls were included. Cerebral blood flow (CBF) map was obtained by pulsed ASL perfusion imaging at 3 T MRI...
October 6, 2016: Brain Imaging and Behavior
D Athauda, T Foltynie
There is growing evidence that patients with Type 2 diabetes have an increased risk of developing Parkinson's disease and share similar dysregulated pathways suggesting common underlying pathological mechanisms. Historically insulin was thought solely to be a peripherally acting hormone responsible for glucose homeostasis and energy metabolism. However accumulating evidence indicates insulin can cross the blood-brain-barrier and influence a multitude of processes in the brain including regulating neuronal survival and growth, dopaminergic transmission, maintenance of synapses and pathways involved in cognition...
October 3, 2016: Progress in Neurobiology
Lionel Carneiro, Sarah Geller, Audrey Hébert, Cendrine Repond, Xavier Fioramonti, Corinne Leloup, Luc Pellerin
Ketone bodies have been shown to transiently stimulate food intake and modify energy homeostasis regulatory systems following cerebral infusion for a moderate period of time (<6 hours). As ketone bodies are usually enhanced during episodes of fasting, this effect might correspond to a physiological regulation. In contrast, ketone bodies levels remain elevated for prolonged periods during obesity, and thus could play an important role in the development of this pathology. In order to understand this transition, ketone bodies were infused through a catheter inserted in the carotid to directly stimulate the brain for a period of 24 hours...
October 6, 2016: Scientific Reports
Keri S Taylor, Hisayoshi Murai, Philip J Millar, Nobuhiko Haruki, Derek S Kimmerly, Beverley L Morris, George Tomlinson, T Douglas Bradley, John S Floras
Obstructive apnea during sleep elevates the set point for efferent sympathetic outflow during wakefulness. Such resetting is attributed to hypoxia-induced upregulation of peripheral chemoreceptor and brain stem sympathetic function. Whether recurrent arousal from sleep also influences daytime muscle sympathetic nerve activity is unknown. We therefore tested, in a cohort of 48 primarily nonsleepy, middle-aged, male (30) and female (18) volunteers (age: 59±1 years, mean±SE), the hypothesis that the frequency of arousals from sleep (arousal index) would relate to daytime muscle sympathetic burst incidence, independently of the frequency of apnea or its severity...
October 3, 2016: Hypertension
Anastasiya Slyepchenko, Michael Maes, Rodrigo Machado-Veira, George Anderson, Marco Solmi, Yolanda Sanz, Michael Berk, Cristiano A Köhler, André F Carvalho
The comorbid prevalence of major depressive disorder (MDD) with obesity and type II diabetes mellitus reflects the existence of a subset of individuals with a complex common pathophysiology and overlapping risk factors. Such comorbid disease presentations imply a number of difficulties, including: decreased treatment responsivity and adherence; altered glycemic control and increased risk of wider medical complications. A number of factors link MDD to metabolic-associated disorders, including: higher rates of shared risk factors such as poor diet and physical inactivity and biological elements including increased inflammation; insulin resistance; oxidative and nitrosative stress; and mitochondrial dysfunction...
September 22, 2016: Current Pharmaceutical Design
Shokei Kim-Mitsuyama
There is accumulating evidence that RAS inhibitors not only reduce blood pressure, but also exert pleiotropic effects, including a renoprotective effect, amelioration of insulin resistance, reduction in onset of diabetes, and suppression of cardiovascular remodelling,. However, the definite benefit of RAS inhibition in treatment of hypertension with CKD or DM is not conclusive. We previously performed the OlmeSartan and Calcium Antagonists Randomized (OSCAR) study comparing the preventive effect of high-dose ARB therapy versus ARB plus CCB combination therapy on cardiovascular morbidity and mortality in 1164 Japanese elderly hypertensive patients with baseline type 2 diabetes and/or CVD (Am J Med (2012))...
September 2016: Journal of Hypertension
Erica N Chirico, Vanessa Di Cataldo, Fabien Chauveau, Alain Geloën, David Patsouris, Benoît Thézé, Cyril Martin, Hubert Vidal, Jennifer Rieusset, Vincent Pialoux, Emmanuelle Canet-Soulas
BACKGROUND: Vascular brain lesions, present in advanced atherosclerosis, share pathological hallmarks with peripheral vascular lesions, such as increased inflammation and oxidative stress. Physical activity reduces these peripheral risk factors, but its cerebrovascular effect is less documented, especially by non-invasive imaging. OBJECTIVES: Through a combination of in-vivo and post-mortem techniques, we aimed at characterizing vascular brain damage in old ApoE(-/-) mice fed a high cholesterol (HC) diet with dietary controlled intake...
September 19, 2016: Journal of Physiology
Lesley-Anne Bissell, Elizabeth M A Hensor, Lukasz Kozera, Sarah L Mackie, Agata N Burska, Jacqueline L Nam, Helen Keen, Edith Villeneuve, Helena Donica, Maya H Buch, Philip G Conaghan, Jacqueline Andrews, Paul Emery, Ann W Morgan
OBJECTIVES: To determine the change in established biomarkers of cardiovascular (CV) risk, namely, total cholesterol/high-density lipoprotein cholesterol ratio (TC/HDL-C), N-terminal pro-brain natriuretic peptide (NT-proBNP) and insulin resistance (IR) in patients with early RA treated with two different treat-to-target strategies. METHODS: Fasting glucose, lipids, insulin and NT-proBNP were measured at baseline, weeks 26 and 78 in 79 DMARD-naïve RA patients, free of CV disease, as part of a double-blind randomized controlled trial of MTX with either infliximab (IFX) or methylprednisolone as induction therapy...
September 16, 2016: Rheumatology
André Kleinridders
Insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R) are highly conserved receptor tyrosine kinases, which share signalling proteins and are ubiquitously expressed in the brain. Central application of insulin or IGF1 exerts several similar physiological outcomes, varying in strength, whereas disruption of the corresponding receptors in the brain leads to remarkably different effects on brain size and physiology, thus pointing to unique effects of the corresponding hormone receptors. Central insulin/IGF1 resistance impacts various levels of the IR/IGF1R signalling pathways and is a feature of metabolic syndrome and neurodegenerative diseases such as Alzheimer's disease...
September 15, 2016: Journal of Neuroendocrinology
Ruth I Versteeg, Karin E Koopman, Jan Booij, Mariëtte T Ackermans, Unga A Unmehopa, Eric Fliers, Susanne E la Fleur, Mireille J Serlie
BACKGROUND: Altered brain dopaminergic and serotonergic pathways have been shown in obese rodents and humans, but it is unknown whether this is related to obesity per se or to the metabolic derangements associated with obesity. METHODS: We performed a case-control study in insulin sensitive obese (ISO) and insulin resistant obese (IRO) subjects (n = 12) and age-matched lean controls (n = 8) and measured serotonin transporter (SERT) binding in the whole diencephalon and specifically in the hypothalamus, as well as dopamine transporter (DAT) binding in the striatum using 123I-FP-CIT single photon emission computed tomography (SPECT)...
September 14, 2016: Neuroendocrinology
Fabio Di Domenico, Eugenio Barone, Marzia Perluigi, D Allan Butterfield
SIGNIFICANCE: Alzheimer disease (AD), a multifactorial neurodegenerative disorder that represents the most disabling condition in the aged, shares many features of insulin resistance diseases, suggesting AD can be considered a metabolic disease, characterized by reduced insulin signaling, increased oxidative stress, pro-inflammatory cytokine activation, mitochondrial dysfunction, impaired energy metabolism, and altered protein homeostasis. RECENT ADVANCES: Reduced glucose utilization and energy metabolism in AD has been associated with accumulation of Aβ and hyperphosphorylated tau, increased oxidative stress, and accumulation of unfolded/misfolded proteins...
September 14, 2016: Antioxidants & Redox Signaling
Torsten P M Scheithauer, Geesje M Dallinga-Thie, Willem M de Vos, Max Nieuwdorp, Daniël H van Raalte
OBJECTIVE: The twin pandemics of obesity and Type 2 diabetes (T2D) are a global challenge for health care systems. Changes in the environment, behavior, diet, and lifestyle during the last decades are considered the major causes. A Western diet, which is rich in saturated fat and simple sugars, may lead to changes in gut microbial composition and physiology, which have recently been linked to the development of metabolic diseases. METHODS: We will discuss evidence that demonstrates the influence of the small and large intestinal microbiota on weight regulation and the development of insulin resistance, based on literature search...
September 2016: Molecular Metabolism
Agata Mierzwicka, Marek Bolanowski
Among new peptides responsible for the pathogenesis of metabolic disorders and carbohydrate metabolism, adipokines are of great importance. Adipokines are substances of hormonal character, secreted by adipose tissue. Apart from the well-known adipokines, adropin and preptin are relatively newly discovered, hence their function is not fully understood. They are peptides not secreted by adipose tissue but their role in the metabolic regulations seems to be significant. Preptin is a 34-amino acid peptide, a derivative of proinsulin growth factor II (pro-IGF-II), secreted by pancreatic β cells, considered to be a physiological enhancer of insulin secretion...
2016: Postȩpy Higieny i Medycyny Doświadczalnej
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