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https://www.readbyqxmd.com/read/29165354/the-role-of-glucagon-like-peptide-1-glp1-in-type-3-diabetes-glp-1-controls-insulin-resistance-neuroinflammation-and-neurogenesis-in-the-brain
#1
REVIEW
Choon Sang Bae, Juhyun Song
Alzheimer's disease (AD), characterized by the aggregation of amyloid-β (Aβ) protein and neuroinflammation, is the most common neurodegenerative disease globally. Previous studies have reported that some AD patients show impaired glucose utilization in brain, leading to cognitive decline. Recently, diabetes-induced dementia has been called "type 3 diabetes", based on features in common with those of type 2 diabetes and the progression of AD. Impaired glucose uptake and insulin resistance in the brain are important issues in type 3 diabetes, because these problems ultimately aggravate memory dysfunction in the brain...
November 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29163128/insulin-resistance-and-alzheimer-s-disease-bioenergetic-linkages
#2
REVIEW
Bryan J Neth, Suzanne Craft
Metabolic dysfunction is a well-established feature of Alzheimer's disease (AD), evidenced by brain glucose hypometabolism that can be observed potentially decades prior to the development of AD symptoms. Furthermore, there is mounting support for an association between metabolic disease and the development of AD and related dementias. Individuals with insulin resistance, type 2 diabetes mellitus (T2D), hyperlipidemia, obesity, or other metabolic disease may have increased risk for the development of AD and similar conditions, such as vascular dementia...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29159583/the-association-between-artificial-sweeteners-and-obesity
#3
REVIEW
Michelle Pearlman, Jon Obert, Lisa Casey
PURPOSE OF REVIEW: The purpose of this paper is to review the epidemiology of obesity and the evolution of artificial sweeteners; to examine the latest research on the effects of artificial sweeteners on the host microbiome, the gut-brain axis, glucose homeostasis, and energy consumption; and to discuss how all of these changes ultimately contribute to obesity. RECENT FINDINGS: Although artificial sweeteners were developed as a sugar substitute to help reduce insulin resistance and obesity, data in both animal models and humans suggest that the effects of artificial sweeteners may contribute to metabolic syndrome and the obesity epidemic...
November 21, 2017: Current Gastroenterology Reports
https://www.readbyqxmd.com/read/29159396/association-of-nonalcoholic-fatty-liver-disease-with-lower-brain-volume-in-healthy-middle-aged-adults-in-the-framingham-study
#4
Galit Weinstein, Shira Zelber-Sagi, Sarah R Preis, Alexa S Beiser, Charles DeCarli, Elizabeth K Speliotes, Claudia L Satizabal, Ramachandran S Vasan, Sudha Seshadri
Importance: Nonalcoholic fatty liver disease (NAFLD) is a common condition that is most often asymptomatic. It is associated with metabolic syndrome, incident diabetes, carotid atherosclerosis, and endothelial dysfunction, conditions that in turn are strongly linked with brain damage and cognitive impairment. However, it is not known whether NAFLD is associated with structural brain measures in humans. Objective: To assess the association between prevalent NAFLD and brain magnetic resonance imaging (MRI) measures...
November 20, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/29158110/diabetes-mellitus-and-alzheimer-s-disease-gsk-3%C3%AE-as-a-potential-link
#5
REVIEW
Ying Zhang, Nan-Qu Huang, Fei Yan, Hai Jin, Shao-Yu Zhou, Jing-Shan Shi, Feng Jin
It is well known that Alzheimer's disease (AD) is closely related to diabetes mellitus (DM), and AD is also regarded as Type 3 diabetes (T3D). However, the exact link between AD and DM is still unclear. Recently, more and more evidence has shown that glycogen synthase kinase-3β (GSK-3β) may be the potential link between DM and AD. In DM, GSK-3β is the crucial enzyme of glycogen synthesis, which plays a key role in regulating blood glucose. More importantly, GSK-3β is one of the key factors leading to insulin deficiency and insulin resistance, and insulin resistance is an important hallmark of the occurrence and development of DM...
November 20, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29154269/early-and-persistent-o-glcnac-protein-modification-in-the-streptozotocin-model-of%C3%A2-alzheimer-s-disease
#6
João Paulo Almeida Dos Santos, Adriana Vizuete, Fernanda Hansen, Regina Biasibetti, Carlos-Alberto Gonçalves
 O-GlcNAc transferase (OGT), an enzyme highly expressed in brain tissue, catalyzes the addition of N-acetyl-glucosamine (GlcNAc) to hydroxyl residues of serine and threonine of proteins. Brain protein O-GlcNAcylation is diminished in Alzheimer's disease (AD), and OGT targets include proteins of the insulin-signaling pathway (e.g., insulin receptor susbtrate-1, IRS-1). We hypothesized that ICV streptozotocin (STZ) also affects O-GlcNAc protein modification. We investigated hippocampal metabolic changes in Wistar rats, particularly OGT levels and insulin resistance, as well as related astroglial activities, immediately after ICV STZ administration (first week) and later on (fourth week)...
November 16, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29141949/microvascular-insulin-resistance-in-skeletal-muscle-and-brain-occurs-early-in-the-development-of-juvenile-obesity-in-pigs
#7
T Dylan Olver, Zachary Ian Grunewald, Thomas J Jurrissen, Rebecca Ek MacPherson, Paul J LeBlanc, Teagan R Schnurbusch, Alana M Czajkowski, Maurice Harold Laughlin, R Scott Rector, Shawn B Bender, Eric M Walters, Craig A Emter, Jaume Padilla
BACKGROUND: Impaired microvascular insulin signaling may develop prior to overt indices of microvascular endothelial dysfunction and represent an early pathological feature of adolescent obesity. Using a translational porcine model of juvenile obesity, we tested the hypotheses that in the early stages of obesity development, impaired insulin signaling manifests in skeletal muscle (triceps), brain (prefrontal cortex) and corresponding vasculatures, and that depressed insulin-induced vasodilation is reversible with acute inhibition of protein kinase C beta (PKCβ)...
November 15, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29138510/high-fat-diet-induced-obesity-and-insulin-resistance-are-characterized-by-differential-beta-oscillatory-signaling-of-the-limbic-cortico-basal-ganglia-loop
#8
Lukas Maurer, Hui Tang, Jens K Haumesser, Jennifer Altschüler, Andrea A Kühn, Joachim Spranger, Christoph van Riesen
The concept of brain circuit disorders has been proposed for a variety of neuropsychiatric diseases, characterized by pathological disturbances of neuronal networks including changes in oscillatory signaling of re-entrant cortico-subcortical loops in the basal ganglia system. Parts of this circuitry play a pivotal role in energy homeostasis. We therefore investigated whether high-fat diet (HFD) induced obesity is associated with changes in oscillatory signaling in the limbic cortico-basal ganglia loop. We performed multi-site in-vivo electrophysiological recordings of local field potentials within this network under urethane anesthesia in adult rats after 4 weeks of HFD feeding compared to age-matched controls...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29132997/thyroid-hormone-improves-insulin-signaling-and-reduces-the-activation-of-neurodegenerative-pathway-in-the-hippocampus-of-diabetic-adult-male-rats
#9
Fernanda Prieto-Almeida, Ana Carolina Panveloski-Costa, Fernanda Crunfli, Silvania da Silva Teixeira, Maria Tereza Nunes, Andréa da Silva Torrão
AIMS: Diabetes mellitus (DM) and impairments of glucose metabolism and insulin resistance in the brain have been suggested as a likely etiology of Alzheimer's disease (AD). Studies have shown that thyroid hormones (THs) improve insulin sensitivity in DM rats and act as mediators of the plasticity of the nervous system altering behavior and cognitive function. Based on these findings, this study aimed to evaluate the effects of diabetes and triiodothyronine (T3) treatment upon proteins associated with DM and AD in the central nervous system...
November 10, 2017: Life Sciences
https://www.readbyqxmd.com/read/29126250/diabetic-microvascular-disease-an-endocrine-society-scientific-statement
#10
Eugene J Barrett, Zhenqi Liu, Mogher Khamaisi, George L King, Ronald Klein, Barbara E K Klein, Timothy M Hughes, Suzanne Craft, Barry I Freedman, Donald W Bowden, Aaron I Vinik, Carolina M Casellini
Both type 1 and type 2 diabetes adversely affect the microvasculature in multiple organs. Our understanding of the genesis of this injury and of potential interventions to prevent, limit, or reverse injury/dysfunction is continuously evolving. This statement reviews biochemical/cellular pathways involved in facilitating and abrogating microvascular injury. The statement summarizes the types of injury/dysfunction that occur in the three classical diabetes microvascular target tissues, the eye, the kidney, and the peripheral nervous system; the statement also reviews information on the effects of diabetes and insulin resistance on the microvasculature of skin, brain, adipose tissue, and cardiac and skeletal muscle...
November 8, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29113464/a-new-treatment-strategy-for-parkinson-s-disease-through-the-gut-brain-axis-the-glucagon-like-peptide-1-receptor-pathway
#11
Dong Seok Kim, Ho-Il Choi, Yun Wang, Yu Luo, Barry J Hoffer, Nigel H Greig
Molecular communications in the gut-brain axis, between the central nervous system and the gastrointestinal tract, are critical for maintaining healthy brain function, particularly in aging. Epidemiological analyses indicate type 2 diabetes mellitus (T2DM) is a risk factor for neurodegenerative disorders including Alzheimer's disease (AD) and Parkinson's diseases (PD) for which aging shows a major correlative association. Common pathophysiological features exist between T2DM, AD, and PD, including oxidative stress, inflammation, insulin resistance, abnormal protein processing, and cognitive decline, and suggest that effective drugs for T2DM that positively impact the gut-brain axis could provide an effective treatment option for neurodegenerative diseases...
September 2017: Cell Transplantation
https://www.readbyqxmd.com/read/29108865/insulin-expression-in-cultured-astrocytes-and-the-decrease-by-amyloid-%C3%AE
#12
Katsura Takano, Keisuke Koarashi, Kenji Kawabe, Masanori Itakura, Hidemitsu Nakajima, Mitsuaki Moriyama, Yoichi Nakamura
Insulin resistance in brain has been reported in Alzheimer's diseases (AD). Insulin signaling is important for homeostasis in brain function and reported to be disturbed in neurons leading to tau phosphorylation and neurofibrillary tangles. Many investigations of insulin in neurons have been reported; however, it has not been reported whether astrocytes also produce insulin. In the present study, we assessed the expression of insulin in astrocytes cultured from rat embryonic brain and the effects of amyloid β1-42 (Aβ) and lipopolysaccharide (LPS) on the expression...
November 8, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29107872/inflammation-and-gut-brain-axis-link-obesity-to-cognitive-dysfunction-plausible-pharmacological-interventions
#13
REVIEW
Maite Solas, Fermin I Milagro, María J Ramírez, J Alfredo Martínez
Obesity prevalence is increasing steadily throughout the world's population in most countries and in parallel the prevalence of metabolic disorders including cardiovascular diseases and type 2 diabetes is also rising, but less is reported about excessive adiposity relationship with poorer cognitive performance, cognitive decline and dementia. Some human clinical studies have evidenced that obesity is related to the risk of the development of mild cognitive impairment, in the form of short-term memory and executive function deficits, as well as dementia and Alzheimer's disease...
November 3, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29083297/in-male-rats-the-ability-of-central-insulin-to-suppress-glucose-production-is-impaired-by-olanzapine-whereas-glucose-uptake-is-left-intact
#14
Chantel Kowalchuk, Celine Teo, Virginia Wilson, Araba Chintoh, Loretta Lam, Sri Mahavir Agarwal, Adria Giacca, Gary J Remington, Margaret K Hahn
BACKGROUND: Insulin receptors are widely expressed in the brain and may represent a crossroad between metabolic and cognitive disorders. Although antipsychotics, such as olanzapine, are the cornerstone treatment for schizophrenia, they are associated with high rates of type 2 diabetes and lack efficacy for illness-related cognitive deficits. Historically, this risk of diabetes was attributed to the weight gain propensity of antipsychotics, but recent work suggests antipsychotics can have weight-independent diabetogenic effects involving unknown brain-mediated mechanisms...
November 2017: Journal of Psychiatry & Neuroscience: JPN
https://www.readbyqxmd.com/read/29076435/andrographolide-reorganise-hyperglycaemia-and-distorted-antioxidant-profile-in-streptozotocin-induced-diabetic-rats
#15
Ramavat Ravindhar Naik, Praveen Kumar Munipally, Turlapati Nagaraju
Diabetes mellitus (DM) is a constant and illimitable metabolic disorder that can happen even at a young age due to the virtual absence of naturally acting insulin, which uptakes and accumulates glucose; thereby reduce the use of glucose. In the present study, we evaluated the neuroprotective efficacy of andrographolide on streptozotocin (STZ) induced diabetic Sprague dawley rats. Diabetes was induced by intraperitonial injection of STZ (45 mg/kg B.W) in Sprague dawley rats. Andrographolide (2.5 mg/kg B.W) was administered orally to diabetic rats and Glibenclamide (25mg/kg B...
October 26, 2017: Cardiovascular & Hematological Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29058763/s14g-humanin-alleviates-insulin-resistance-and-increases-autophagy-in-neurons-of-app-ps1-transgenic-mouse
#16
Kun Han, Ning Jia, Yi Zhong, Xiuli Shang
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by Aβ plaque deposition in the brain, which is related to the disorder of autophagosome maturation, transport and formation of autolysosome. Notably, abnormal insulin signaling is connected with cognitive dysfunction in AD. In this study, using APP/PS1 transgenic mice as AD model, we investigated the mechanism by which S14G-humanin (HNG) improved autophagy and insulin signaling in AD brain. Immunohistochemistry was used to determine the levels of mTOR and Aβ deposition, and Western blot analysis was used to determine IRS-1, IRS-1 pSEr636, ULK1, p62, LC3 I/LC3 II protein levels...
October 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29054390/oral-pioglitazone-ameliorates-fructose-induced-peripheral-insulin-resistance-and-hippocampal-gliosis-but-not-restores-inhibited-hippocampal-adult-neurogenesis
#17
Wen-Chung Liu, Chih-Wei Wu, You-Lin Tain, Mu-Hui Fu, Chun-Ying Hung, I-Chun Chen, Lee-Wei Chen, Kay L H Wu
Diet-associated insulin resistance (IR) is intimately correlated with the progression of metabolic syndrome and hippocampal dysfunction. Pioglitazone (PIO), a selective peroxisome proliferator-activated receptor gamma (PPARγ) agonist, has been applied to enhance insulin sensitivity. With limited permeability to blood-brain-barrier, it is unclear that whether oral PIO available to cure both the peripheral IR and the impairment in the hippocampus. We evaluated the levels of peripheral and hippocampal IR via the homeostatic model assessment of insulin resistance and hippocampal IRS-1/Akt phosphorylation, respectively, of Wistar Kyoto rats fed with a regular chew or high fructose diet (HFD) for 12weeks...
October 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29053851/escitalopram-ameliorates-hypercortisolemia-and-insulin-resistance-in-low-birth-weight-men-with-limbic-brain-alterations
#18
Christian Selmer Buhl, Hans Stødkilde-Jørgensen, Poul Videbech, Allan Vaag, Niels Møller, Sten Lund, Esben Selmer Buhl
CONTEXT: Low birth weight (LBW, <2500 g) is linked to development of insulin resistance and limbic-hypothalamic-pituitary-adrenal (LHPA)-axis hyperactivity. OBJECTIVE: First aim was to study insulin action, LHPA-axis function and limbic brain structures in young, healthy LBW-men vs. normal birth weight controls (NBW) (Part 1). Second aim was to investigate the effects of Escitalopram vs. placebo treatment in LBW with regards to LHPA-axis and insulin sensitivity (Part 2)...
October 18, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29053786/tau-hyperphosphorylation-induces-oligomeric-insulin-accumulation-and-insulin-resistance-in-neurons
#19
Patricia Rodriguez-Rodriguez, Anna Sandebring-Matton, Paula Merino-Serrais, Cristina Parrado-Fernandez, Alberto Rabano, Bengt Winblad, Jesús Ávila, Isidre Ferrer, Angel Cedazo-Minguez
Insulin signalling deficiencies and insulin resistance have been directly linked to the progression of neurodegenerative disorders like Alzheimer's disease. However, to date little is known about the underlying molecular mechanisms or insulin state and distribution in the brain under pathological conditions. Here, we report that insulin is accumulated and retained as oligomers in hyperphosphorylated tau-bearing neurons in Alzheimer's disease and in several of the most prevalent human tauopathies. The intraneuronal accumulation of insulin is directly dependent on tau hyperphosphorylation, and follows the tauopathy progression...
October 13, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29051736/novel-peripherally-restricted-cannabinoid-1-receptor-selective-antagonist-txx-522-with-prominent-weight-loss-efficacy-in-diet-induced-obese-mice
#20
Wei Chen, Fengchun Shui, Cheng Liu, Xinbo Zhou, Wei Li, Zhibing Zheng, Wei Fu, Lili Wang
The clinical development of the first generation of globally active cannabinoid 1 receptor (CB1R) antagonists was suspended because of their adverse neuropsychiatric effects. Selective blockade of peripheral CB1Rs has the potential to provide a viable strategy for the treatment of severe obesity while avoiding these central nervous system side effects. In the current study, a novel compound (TXX-522) was rationally designed based on the parent nucleus of a classical CB1R-selective antagonist/inverse agonist, rimonabant (SR141716A)...
2017: Frontiers in Pharmacology
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