The Role of Insulin and Incretins in Neuroinflammation and Neurodegeneration

Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotrophic polypeptide (GIP) are incretin hormones secreted from intestinal cells in response to incoming nutrients. The release of these incretins triggers the production and secretion of insulin from pancreatic β cells, which upregulates the transport of glucose from the blood stream into the muscles, liver and adipose tissue for storage; therefore, insulin and incretins are vital to maintaining energy homeostasis within the body. Recently, it has been recognized that the activity of these hormones is not limited to the periphery, but extends to the central nervous system (CNS) as well. Within the CNS, insulin and incretins function as components of the anti-apoptotic and growth-regulating signaling cascades. Moreover, anti-inflammatory and neuroprotective roles for these hormones in the CNS have also been demonstrated. Specific discoveries have been made suggesting that insulin, GLP-1 and GIP may inhibit pathological processes in several CNS diseases, such as Alzheimer’s disease, Parkinson’s disease, and schizophrenia.

• Publication year

  2014

• Venue

  Unknown venue

• Publication date

  2014-10-30

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.14800/IE.391
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

• Inflammation and insulin/IGF-1 resistance as the possible link between obesity and neurodegeneration.

  2014cited by this paper
• Insulin treatment normalizes retinal neuroinflammation but not markers of synapse loss in diabetic rats.

  2014cited by this paper
• Liraglutide can reverse memory impairment, synaptic loss and reduce plaque load in aged APP/PS1 mice, a model of Alzheimer's disease.

  2014cited by this paper
• The nursing role in the use of insulin coma therapy for schizophrenia in Britain, 1936-1965.

  2014cited by this paper
• Protection of streptozotocin induced insulin receptor dysfunction, neuroinflammation and amyloidogenesis in astrocytes by insulin.

  2014influential reference
• Neuroprotective and anti‐apoptotic effects of liraglutide on SH‐SY5Y cells exposed to methylglyoxal stress

  2014cited by this paper
• Exenatide Treatment Exerts Anxiolytic- and Antidepressant-Like Effects and Reverses Neuropathy in a Mouse Model of Type-2 Diabetes

  2014cited by this paper
• Simultaneous GLP-1 and Insulin Administration Acutely Enhances Their Vasodilatory, Antiinflammatory, and Antioxidant Action in Type 2 Diabetes

  2014cited by this paper
• Crosstalk Between Insulin and Toll-like Receptor Signaling Pathways in the Central Nervous system

  2014cited by this paper
• Insulin on hydrogen peroxide-induced oxidative stress involves ROS/Ca2+ and Akt/Bcl-2 signaling pathways

  2014cited by this paper
• Insulin alleviates the inflammatory response and oxidative stress injury in cerebral tissues in septic rats

  2014cited by this paper
• Insulin Blocks Glutamate-Induced Neurotoxicity in Differentiated SH-SY5Y Neuronal Cells

  2014cited by this paper
• Exenatide and the treatment of patients with Parkinson's disease.

  2013cited by this paper
• Stress contributes to the development of central insulin resistance during aging: implications for Alzheimer's disease.

  2013cited by this paper
• Brain Insulin Dysregulation: Implication for Neurological and Neuropsychiatric Disorders

  2013cited by this paper
• Glucose-dependent insulinotropic polypeptide induces cytokine expression, lipolysis, and insulin resistance in human adipocytes.

  2013cited by this paper
• Adding Once-Daily Lixisenatide for Type 2 Diabetes Inadequately Controlled by Established Basal Insulin

  2013cited by this paper
• Intranasal Insulin as a Treatment for Alzheimer’s Disease: A Review of Basic Research and Clinical Evidence

  2013cited by this paper
• Antipsychotic-like effect of GLP-1 agonist liraglutide but not DPP-IV inhibitor sitagliptin in mouse model for psychosis.

  2013cited by this paper
• The incretin analogue D-Ala2GIP reduces plaque load, astrogliosis and oxidative stress in an APP/PS1 mouse model of Alzheimer's disease.

  2013cited by this paper
• Sustained Alzheimer's Amyloid Pathology in Myeloid Differentiation Protein-88-Deficient APPswe/PS1 Mice

  2013cited by this paper
• Neuroprotective effects of D-Ala2GIP on Alzheimer's disease biomarkers in an APP/PS1 mouse model

  2013influential reference
• Insulin inhibits lipopolysaccharide-induced nitric oxide synthase expression in rat primary astrocytes.

  2013cited by this paper
• D-Ala2GIP Facilitated Synaptic Plasticity and Reduces Plaque Load in Aged Wild Type Mice and in an Alzheimer's Disease Mouse Model

  2013cited by this paper
• he neuroprotective effects of GLP-1 : Possible treatments for cognitive deficits in ndividuals with mood disorders oger

  2012cited by this paper
• Liraglutide, a Long-Acting GLP-1 Mimetic, and its Metabolite Attenuate Inflammation after Intracerebral Hemorrhage

  2012cited by this paper
• Drugs developed to treat diabetes, liraglutide and lixisenatide, cross the blood brain barrier and enhance neurogenesis

  2012cited by this paper
• Changes in insulin-signaling transduction pathway underlie learning/memory deficits in an Alzheimer’s disease rat model

  2012cited by this paper
• Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial.

  2012cited by this paper
• Exendin-4, a glucagon-like peptide-1 receptor agonist, provides neuroprotection in mice transient focal cerebral ischemia

  2012cited by this paper
• Use of insulin sensitizers for the treatment of major depressive disorder: a pilot study of pioglitazone for major depression accompanied by abdominal obesity.

  2012cited by this paper
• Glucagon-like peptide-1 inhibits adipose tissue macrophage infiltration and inflammation in an obese mouse model of diabetes

  2012cited by this paper
• Liraglutide for the treatment of type 2 diabetes.

  2011cited by this paper
• The Diabetes Drug Liraglutide Prevents Degenerative Processes in a Mouse Model of Alzheimer's Disease

  2011cited by this paper
• Native incretins prevent the development of atherosclerotic lesions in apolipoprotein E knockout mice

  2011cited by this paper
• Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment A Pilot Clinical Trial

  2011cited by this paper
• Altered levels of circulating insulin and other neuroendocrine hormones associated with the onset of schizophrenia.

  2011cited by this paper
• Insulin resistance impairs nigrostriatal dopamine function.

  2011cited by this paper
• Defects in IGF-1 receptor, insulin receptor and IRS-1/2 in Alzheimer's disease indicate possible resistance to IGF-1 and insulin signalling.

  2010cited by this paper
• Rosiglitazone Add-On in Treatment of Depressed Patients with Insulin Resistance: a Pilot Study

  2010cited by this paper
• GIP and GLP‐1, the two incretin hormones: Similarities and differences

  2010cited by this paper
• Enhancing the GLP‐1 receptor signaling pathway leads to proliferation and neuroprotection in human neuroblastoma cells

  2010cited by this paper
• Akt-dependent and isoform-specific regulation of dopamine transporter cell surface expression.

  2010cited by this paper
• Central nervous insulin resistance: a promising target in the treatment of metabolic and cognitive disorders?

  2009cited by this paper
• Evidence for beneficial effects of compromised gastric inhibitory polypeptide action in obesity-related diabetes and possible therapeutic implications

  2009cited by this paper
• Insulin exhibits short-term anti-inflammatory but long-term proinflammatory effects in vitro.

  2009cited by this paper
• Glucose‐dependent insulinotropic polypeptide (GIP) and its receptor (GIPR): Cellular localization, lesion‐affected expression, and impaired regenerative axonal growth

  2009cited by this paper
• Insulin-induced NADPH oxidase activation promotes proliferation and matrix metalloproteinase activation in monocytes/macrophages.

  2009cited by this paper
• Intracerebroventricular insulin improves spatial learning and memory in male Wistar rats.

  2009cited by this paper
• GLP-1 receptor stimulation preserves primary cortical and dopaminergic neurons in cellular and rodent models of stroke and Parkinsonism

  2009cited by this paper
• Does neuroinflammation fan the flame in neurodegenerative diseases?

  2009cited by this paper
• Receptors for the incretin glucagon-like peptide-1 are expressed on neurons in the central nervous system

  2009cited by this paper
• Protease-resistant glucose-dependent insulinotropic polypeptide agonists facilitate hippocampal LTP and reverse the impairment of LTP induced by beta-amyloid.

  2008cited by this paper
• Insulin increases the release of proinflammatory mediators.

  2008cited by this paper
• Intranasal Insulin Administration Dose-Dependently Modulates Verbal Memory and Plasma Amyloid-β in Memory-Impaired Older Adults

  2008cited by this paper
• GLP-1 agonists facilitate hippocampal LTP and reverse the impairment of LTP induced by beta-amyloid.

  2008cited by this paper
• Hypoinsulinemia Regulates Amphetamine-Induced Reverse Transport of Dopamine

  2007cited by this paper
• Performing a Cure for Schizophrenia: Insulin Coma Therapy on the Wards

  2007cited by this paper
• Intranasal Insulin to Improve Memory Function in Humans

  2007cited by this paper
• Immunohistochemical distribution of glucose‐dependent insulinotropic polypeptide in the adult rat brain

  2007cited by this paper
• Review of sitagliptin phosphate: a novel treatment for type 2 diabetes

  2007cited by this paper
• Glucagon-like peptide-1 inhibits LPS-induced IL-1beta production in cultured rat astrocytes.

  2006cited by this paper
• The extracellular signal-regulated kinase: Multiple substrates regulate diverse cellular functions

  2006cited by this paper
• Early activation of microglia as antigen-presenting cells correlates with T cell-mediated protection and repair of the injured central nervous system.

  2004cited by this paper
• Expression, regulation, and function of IGF-1, IGF-1R, and IGF-1 binding proteins in blood vessels.

  2004cited by this paper
• Glial cells.

  2004cited by this paper
• The source of cerebral insulin.

  2004cited by this paper
• Passage of VIP/PACAP/secretin family across the blood-brain barrier: therapeutic effects.

  2004cited by this paper
• Astrocytes and Brain Injury

  2003cited by this paper
• Insulin prevents depolarization of the mitochondrial inner membrane in sensory neurons of type 1 diabetic rats in the presence of sustained hyperglycemia.

  2003cited by this paper
• Muscarinic Potentiation of GABAA Receptor Currents Is Gated by Insulin Signaling in the Prefrontal Cortex

  2003cited by this paper
• Redundancy of Radioresistant Signaling Pathways Originating from Insulin-like Growth Factor I Receptor*

  2002cited by this paper
• The glucagon-like peptides: a new genre in therapeutic targets for intervention in Alzheimer's disease

  2002cited by this paper
• Interactions of glucagon-like peptide-1 (GLP-1) with the blood-brain barrier

  2002cited by this paper
• Insulin inhibits intranuclear nuclear factor kappaB and stimulates IkappaB in mononuclear cells in obese subjects: evidence for an anti-inflammatory effect?

  2001cited by this paper
• Insulin Inhibits Intranuclear Nuclear Factor κB and Stimulates IκB in Mononuclear Cells in Obese Subjects: Evidence for an Anti-inflammatory Effect?

  2001cited by this paper
• Evaluation of CSF-tau and CSF-Abeta42 as diagnostic markers for Alzheimer disease in clinical practice.

  2001cited by this paper
• Improving Influence of Insulin on Cognitive Functions in Humans

  2001cited by this paper
• Insulin Up-regulates Tumor Necrosis Factor-α Production in Macrophages through an Extracellular-regulated Kinase-dependent Pathway*

  2001cited by this paper
• NF‐κB activation through IKK‐i‐dependent I‐TRAF/TANK phosphorylation

  2000cited by this paper
• Insulin receptors and insulin action in the brain: review and clinical implications.

  2000cited by this paper
• Insulin receptor‐deficient cells as a new tool for dissecting complex interplay in insulin and insulin‐like growth factors

  1998cited by this paper
• NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses.

  1998cited by this paper
• A theoretical approach to the bell-shaped dependency of cell proliferation on the hormone concentration.

  1997cited by this paper
• Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases.

  1997cited by this paper
• Recruitment of functional GABAA receptors to postsynaptic domains by insulin

  1997cited by this paper
• Mechanism of Insulin and IGF‐I

  1995cited by this paper
• Mechanism of insulin and IGF-I receptor activation and signal transduction specificity. Receptor dimer cross-linking, bell-shaped curves, and sustained versus transient signaling.

  1995cited by this paper
• Effect of Long‐Lasting Diabetes Mellitus on Rat and Human Brain Monoamines

  1990cited by this paper
• Immunohistochemical localization of glucagon-like peptide 1

  1987cited by this paper
• Electronimmunocytochemical evidence for the K cell localization of gastric inhibitory polypeptide (GIP) im man

  1978cited by this paper
• Regulation of blood glucose concentration: hepatic action of insulin.

  1961cited by this paper
• Histological observations on the relation of insulin to the deposition of glycogen in adipose tissue.

  1948cited by this paper

• Western-style diet does not negatively affect the healthy aging benefits of lifelong restrictive feeding

  2022cites this paper
• Cost-effectiveness of the add-on exenatide to conventional treatment in patients with Parkinson’s disease when considering the coexisting effects of diabetes mellitus

  2022cites this paper
• Insights on the modulatory role of Ayurveda-based herbal preparations on gut microbiome and neuroprotection

  2021cites this paper
• Gene therapy-mediated enhancement of protective protein expression for the treatment of Alzheimer's disease.

  2021cites this paper
• Enolase inhibition alters metabolic hormones and inflammatory factors to promote neuroprotection in spinal cord injury.

  2020influential citation
• Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health

  2019cites this paper
• Unhealthy gut, unhealthy brain: The role of the intestinal microbiota in neurodegenerative diseases

  2018cites this paper
• EVALUATION OF ANXIOLYTIC AND ANTIDEPRESSANT ACTIVITY OF SITAGLIPTIN AND LINAGLIPTIN IN RATS

  2017cites this paper
• Incretin hormones regulate microglia oxidative stress, survival and expression of trophic factors.

  2017cites this paper
• Glucose-Dependent Insulinotropic Polypeptide Ameliorates Mild Traumatic Brain Injury-Induced Cognitive and Sensorimotor Deficits and Neuroinflammation in Rats

  2016cites this paper
• Relationship between Insulin-Resistance Processing Speed and Specific Executive Function Profiles in Neurologically Intact Older Adults

  2015cites this paper