scholarly journals Targeting the Enteric Nervous System to Treat Metabolic Disorders? “Enterosynes” as Therapeutic Gut Factors

2019 ◽  
Vol 110 (1-2) ◽  
pp. 139-146 ◽  
Author(s):  
Claude Knauf ◽  
Anne Abot ◽  
Eve Wemelle ◽  
Patrice D. Cani
Keyword(s):  
Insulin Resistance ◽  
Nervous System ◽  
Enteric Nervous System ◽  
Proximal Part ◽  
Enteric Neurons ◽  
Diabetic Patients ◽  
Innovative Strategy ◽  
Treatment Of Diabetes

The gut-brain axis is of crucial importance for controlling glucose homeostasis. Alteration of this axis promotes the type 2 diabetes (T2D) phenotype (hyperglycaemia, insulin resistance). Recently, a new concept has emerged to demonstrate the crucial role of the enteric nervous system in the control of glycaemia via the hypothalamus. In diabetic patients and mice, modification of enteric neurons activity in the proximal part of the intestine generates a duodenal hyper-contractility that generates an aberrant message from the gut to the brain. In turn, the hypothalamus sends an aberrant efferent message that provokes a state of insulin resistance, which is characteristic of a T2D state. Targeting the enteric nervous system of the duodenum is now recognized as an innovative strategy for treatment of diabetes. By acting in the intestine, bioactive gut molecules that we called “enterosynes” can modulate the function of a specific type of neurons of the enteric nervous system to decrease the contraction of intestinal smooth muscle cells. Here, we focus on the origins of enterosynes (hormones, neurotransmitters, nutrients, microbiota, and immune factors), which could be considered therapeutic factors, and we describe their modes of action on enteric neurons. This unsuspected action of enterosynes is proposed for the treatment of T2D, but it could be applied for other therapeutic solutions that implicate communication between the gut and brain.

scholarly journals Effect of sodium intake on blood pressure and albuminuria in Type 2 diabetic patients: the role of insulin resistance

Diabetologia ◽  
2003 ◽  
Vol 47 (2) ◽  
pp. 300-303 ◽  
Author(s):  
M. Vedovato ◽  
G. Lepore ◽  
A. Coracina ◽  
A. R. Dodesini ◽  
E. Jori ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Sodium Intake ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic

scholarly journals Acute regulation of intestinal ion transport and permeability in response to luminal nutrients: the role of the enteric nervous system

2020 ◽  
Vol 318 (2) ◽  
pp. G254-G264
Author(s):  
Jean-Baptiste Cavin ◽  
Hailey Cuddihey ◽  
Wallace K. MacNaughton ◽  
Keith A. Sharkey
Keyword(s):  
Nervous System ◽  
Small Intestine ◽  
Ion Transport ◽  
Enteric Nervous System ◽  
Intestinal Permeability ◽  
Barrier Function ◽  
Enteric Neurons ◽  
Nerve Activity ◽  
Mouse Small Intestine

The small intestine regulates barrier function to absorb nutrients while avoiding the entry of potentially harmful substances or bacteria. Barrier function is dynamically regulated in part by the enteric nervous system (ENS). The role of the ENS in regulating barrier function in response to luminal nutrients is not well understood. We hypothesize that the ENS regulates intestinal permeability and ion flux in the small intestine in response to luminal nutrients. Segments of jejunum and ileum from mice were mounted in Ussing chambers. Transepithelial electrical resistance (TER), short-circuit current ( Isc), and permeability to 4-kDa FITC-dextran (FD4) were recorded after mucosal stimulation with either glucose, fructose, glutamine (10 mM), or 5% Intralipid. Mucosal lipopolysaccharide (1 mg/mL) was also studied. Enteric neurons were inhibited with tetrodotoxin (TTX; 0.5 μM) or activated with veratridine (10 μM). Enteric glia were inhibited with the connexin‐43 blocker Gap26 (20 μM). Glucose, glutamine, Intralipid, and veratridine acutely modified Isc in the jejunum and ileum, but the effect of nutrients on Isc was insensitive to TTX. TTX, Gap26, and veratridine treatment did not affect baseline TER or permeability. Intralipid acutely decreased permeability to FD4, while LPS increased it. TTX pretreatment abolished the effect of Intralipid and exacerbated the LPS‐induced increase in permeability. Luminal nutrients and enteric nerve activity both affect ion flux in the mouse small intestine acutely but independently of each other. Neither neuronal nor glial activity is required for the maintenance of baseline intestinal permeability; however, neuronal activity is essential for the acute regulation of intestinal permeability in response to luminal lipids and lipopolysaccharide. NEW & NOTEWORTHY Luminal nutrients and enteric nerve activity both affect ion transport in the mouse small intestine acutely, but independently of each other. Activation or inhibition of the enteric neurons does not affect intestinal permeability, but enteric neural activity is essential for the acute regulation of intestinal permeability in response to luminal lipids and lipopolysaccharide. The enteric nervous system regulates epithelial homeostasis in the small intestine in a time-dependent, region- and stimulus-specific manner.

scholarly journals Primary Cilia Structure Is Prolonged in Enteric Neurons of 5xFAD Alzheimer’s Disease Model Mice

2021 ◽  
Vol 22 (24) ◽  
pp. 13564
Author(s):  
Vu Thu Thuy Nguyen ◽  
Lena Brücker ◽  
Ann-Kathrin Volz ◽  
Julia C. Baumgärtner ◽  
Malena dos Santos Guilherme ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Enteric Nervous System ◽  
Primary Cilium ◽  
Primary Cilia ◽  
Enteric Neurons ◽  
Wild Type ◽  
5Xfad Mice

Neurodegenerative diseases such as Alzheimer’s disease (AD) have long been acknowledged as mere disorders of the central nervous system (CNS). However, in recent years the gut with its autonomous nervous system and the multitude of microbial commensals has come into focus. Changes in gut properties have been described in patients and animal disease models such as altered enzyme secretion or architecture of the enteric nervous system. The underlying cellular mechanisms have so far only been poorly investigated. An important organelle for integrating potentially toxic signals such as the AD characteristic A-beta peptide is the primary cilium. This microtubule-based signaling organelle regulates numerous cellular processes. Even though the role of primary cilia in a variety of developmental and disease processes has recently been recognized, the contribution of defective ciliary signaling to neurodegenerative diseases such as AD, however, has not been investigated in detail so far. The AD mouse model 5xFAD was used to analyze possible changes in gut functionality by organ bath measurement of peristalsis movement. Subsequently, we cultured primary enteric neurons from mutant mice and wild type littermate controls and assessed for cellular pathomechanisms. Neurite mass was quantified within transwell culturing experiments. Using a combination of different markers for the primary cilium, cilia number and length were determined using fluorescence microscopy. 5xFAD mice showed altered gut anatomy, motility, and neurite mass of enteric neurons. Moreover, primary cilia could be demonstrated on the surface of enteric neurons and exhibited an elongated phenotype in 5xFAD mice. In parallel, we observed reduced β-Catenin expression, a key signaling molecule that regulates Wnt signaling, which is regulated in part via ciliary associated mechanisms. Both results could be recapitulated via in vitro treatments of enteric neurons from wild type mice with A-beta. So far, only a few reports on the probable role of primary cilia in AD can be found. Here, we reveal for the first time an architectural altered phenotype of primary cilia in the enteric nervous system of AD model mice, elicited potentially by neurotoxic A-beta. Potential changes on the sub-organelle level—also in CNS-derived neurons—require further investigations.

Insulin-sensitive and insulin-resistant variants in nonobese Japanese type 2 diabetic patients. The role of triglycerides in insulin resistance

Diabetes Care ◽  
1999 ◽  
Vol 22 (12) ◽  
pp. 2100-2101 ◽  
Author(s):  
A. Taniguchi ◽  
M. Fukushima ◽  
M. Sakai ◽  
K. Kataoka ◽  
K. Miwa ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Insulin Resistant ◽  
Type 2 Diabetic

scholarly journals Development, Diversity, and Neurogenic Capacity of Enteric Glia

2022 ◽  
Vol 9 ◽  
Author(s):  
Werend Boesmans ◽  
Amelia Nash ◽  
Kinga R. Tasnády ◽  
Wendy Yang ◽  
Lincon A. Stamp ◽  
...  
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Glial Cells ◽  
Cell Types ◽  
Vital Role ◽  
Enteric Neurons ◽  
Enteric Glia ◽  
Enteric Glial Cells ◽  
Functional Versatility

Enteric glia are a fascinating population of cells. Initially identified in the gut wall as the “support” cells of the enteric nervous system, studies over the past 20 years have unveiled a vast array of functions carried out by enteric glia. They mediate enteric nervous system signalling and play a vital role in the local regulation of gut functions. Enteric glial cells interact with other gastrointestinal cell types such as those of the epithelium and immune system to preserve homeostasis, and are perceptive to luminal content. Their functional versatility and phenotypic heterogeneity are mirrored by an extensive level of plasticity, illustrated by their reactivity in conditions associated with enteric nervous system dysfunction and disease. As one of the hallmarks of their plasticity and extending their operative relationship with enteric neurons, enteric glia also display neurogenic potential. In this review, we focus on the development of enteric glial cells, and the mechanisms behind their heterogeneity in the adult gut. In addition, we discuss what is currently known about the role of enteric glia as neural precursors in the enteric nervous system.

scholarly journals Deficiency of Adiponectin Receptor 2 Reduces Diet-Induced Insulin Resistance but Promotes Type 2 Diabetes

Endocrinology ◽  
2007 ◽  
Vol 148 (2) ◽  
pp. 683-692 ◽  
Author(s):  
Yanfang Liu ◽  
M. Dodson Michael ◽  
Shera Kash ◽  
William R. Bensch ◽  
Brett P. Monia ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Energy Homeostasis ◽  
Diabetic Patients ◽  
High Fat ◽  
Type 2 Diabetic Patients ◽  
Adiponectin Receptor 2 ◽  
Fat Feeding ◽  
Deficient Mice

Adiponectin/adiponectin receptors (AdipoR) are involved in energy homeostasis and inflammatory pathways. To investigate the role of AdipoR2 in metabolic control, we studied the lipid and glucose metabolic phenotypes in AdipoR2-deficient mice. AdipoR2 deletion diminished high-fat diet-induced dyslipidemia and insulin resistance yet deteriorated glucose homeostasis as high-fat feeding continued, which resulted from the failure of pancreatic β-cells to adequately compensate for the moderate insulin resistance. A defect in the AdipoR2 gene may represent a mechanism underlying the etiology of certain subgroups of type 2 diabetic patients who eventually develop overt diabetes, whereas other obese patients do not.

scholarly journals Lipids Abnormality and Type 2 Diabetes Mellitus: Causes and Consequences

2021 ◽  
Author(s):  
Kan Wang ◽  
Fariba Ahmadizar
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Lipid Lowering ◽  
Diabetic Patients ◽  
Apo B ◽  
Lipid Management

Dyslipidemia and diabetes both are important risk factors for cardiovascular disease. Emerging evidence suggests that these two are closely related to each other, the so-called “dyslipidemia-insulin resistance-hyperinsulinemia” cycle. Recently, several new lipid subfractions, such as apolipoprotein (Apo)B, and ApoJ, have been reported to associate with insulin resistance and incident diabetes, which further claim the role of lipid in the pathophysiology of diabetes. Besides, dyslipidemia is also one of the most prevalent diabetic complications. Clinical guidelines have widely recommended lipid management among diabetic patients through lifestyle intervention and lipid-lowering medications, especially statins, to prevent cardiovascular outcomes.

scholarly journals Role of Glycated Hemoglobin on Islets Cell Autoantibody Mediated Insulin Resistance in Type 2 Diabetic Patients

2020 ◽  
Vol 8 (10) ◽  
pp. 2355-2360
Author(s):  
Dr. Saimun Nahar Rumana ◽  
Dr. Mohammad Moniruzzaman ◽  
Dr. Arif Mahmud Jewel ◽  
Dr. Qumruzzaman .
Keyword(s):  
Insulin Resistance ◽  
Glycated Hemoglobin ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic
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