Glucose-sensing mediated by portal GLP-1 receptor is markedly impaired in insulin-resistant obese animals

10.2337/figshare.13063706.v1 ◽

2020 ◽

Author(s):

Ada Admin ◽

Charles-Henri Malbert ◽

Alain Chauvin ◽

Michael Horowitz ◽

Karen L Jones

Keyword(s):

Splenic Vein ◽

Glucose Sensing ◽

Vagal Afferents ◽

Binding Potential ◽

Specific Reference ◽

Glucose Signaling ◽

Insulin Resistant ◽

Neuron Electrophysiology

The glucose portal sensor informs the brain of changes in glucose inflow via vagal afferents that require an activated GLP-1 receptor (GLP-1r). The GLP-1 system is known to be impaired in insulin-resistant conditions and we sought to understand the consequences of GLP-1 resistance on glucose portal signaling. GLP-1-dependent portal glucose signaling was identified, in vivo, using a novel <sup>68</sup>Ga labeled GLP-1r positron-emitting probe that supplied a quantitative in situ tridimensional representation of the portal sensor with specific reference to the receptor density expressed in binding potential units. It also served as a map for single-neuron electrophysiology driven by an image-based abdominal navigation. We determined that, in insulin-resistant animals, portal vagal afferents failed to inhibit their spiking activity during glucose infusion, a GLP-1r-dependent function. This reflected a reduction in portal GLP-1r binding potential, particularly between the splenic vein and the entrance of the liver. We propose that insulin-resistance, through a reduction in GLP-1r density, leads to functional portal desensitization with a consequent suppression of vagal sensitivity to portal glucose.

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Neuropeptide Y Cells Represent a Distinct Glucose-Sensing Population in the Lateral Hypothalamus

Endocrinology ◽

10.1210/en.2011-1307 ◽

2011 ◽

Vol 152 (11) ◽

pp. 4046-4052 ◽

Cited By ~ 23

Author(s):

Oliver J. Marston ◽

Paul Hurst ◽

Mark L. Evans ◽

Denis I. Burdakov ◽

Lora K. Heisler

Keyword(s):

Electrical Activity ◽

Neuropeptide Y ◽

Fluorescent Protein ◽

Regulatory Elements ◽

Glucose Sensing ◽

Hypothalamic Area ◽

Extracellular Glucose ◽

The Brain

The maintenance of appropriate glucose levels is necessary for survival. Within the brain, specialized neurons detect glucose fluctuations and alter their electrical activity. These glucose-sensing cells include hypothalamic arcuate nucleus neurons expressing neuropeptide Y (NPY) and lateral hypothalamic area (LHA) neurons expressing orexin/hypocretins (ORX) or melanin-concentrating hormone (MCH). Within the LHA, a population of NPY-expressing cells exists; however, their ability to monitor energy status is unknown. We investigated whether NPY neurons located in the LHA, a classic hunger center, detect and respond to fluctuations in glucose availability and compared these responses with those of known LHA glucose sensors expressing ORX or MCH. Using mice expressing green fluorescent protein under the control of NPY regulatory elements, we identified LHA NPY cells and explored their anatomical distribution, neurochemical and electrical properties, in vivo responses to fasting and insulin-induced hypoglycemia, and in situ electrical responses to extracellular glucose. We report that NPY, ORX, and MCH are expressed in nonoverlapping populations within the LHA. Subpopulations of LHA NPY neurons were activated in vivo by both a 6-h fast and insulin-induced hypoglycemia. Likewise, increased extracellular glucose suppressed the electrical activity of approximately 70% of LHA NPY neurons in situ, eliciting hyperpolarization and activating background K+ currents. Furthermore, we report that the glucose sensitivity of LHA NPY neurons is significantly different from neighboring ORX and MCH neurons. These data suggest that NPY-expressing cells in the LHA are a novel population of glucose-sensing neurons that represent a new player in the brain circuitry integrating information about glucose homeostasis.

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In vitro and in vivo polysaccharides assembly: ultrastructural and cytochemical study of growing plant cell wall components.

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100083035 ◽

1978 ◽

Vol 36 (2) ◽

pp. 434-435

Author(s):

D. Reis ◽

B. Vian ◽

J. C. Roland

Keyword(s):

Cell Wall ◽

Self Assembly ◽

Plant Cell Wall ◽

Higher Plants ◽

Three Dimensional ◽

Cytochemical Study ◽

Wall Components

Wall morphogenesis in higher plants is a problem still open to controversy. Until now the possibility of a transmembrane control and the involvement of microtubules were mostly envisaged. Self-assembly processes have been observed in the case of walls of Chlamydomonas and bacteria. Spontaneous gelling interactions between xanthan and galactomannan from Ceratonia have been analyzed very recently. The present work provides indications that some processes of spontaneous aggregation could occur in higher plants during the formation and expansion of cell wall.Observations were performed on hypocotyl of mung bean (Phaseolus aureus) for which growth characteristics and wall composition have been previously defined.In situ, the walls of actively growing cells (primary walls) show an ordered three-dimensional organization (fig. 1). The wall is typically polylamellate with multifibrillar layers alternately transverse and longitudinal. Between these layers intermediate strata exist in which the orientation of microfibrils progressively rotates. Thus a progressive change in the morphogenetic activity occurs.

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Three-Dimensional Subcellular Organization of Hepatocytes in Intact Liver: Simultaneous Visualization of Cytoskeletal and Membrane Markers by Confocal Microscopy

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100163903 ◽

1996 ◽

Vol 54 ◽

pp. 288-289

Author(s):

Greg V. Martin ◽

Ann L. Hubbard

Keyword(s):

Three Dimensional ◽

Integral Membrane Proteins ◽

Polarized Secretion ◽

Microscope Images ◽

Computer Aided ◽

Intracellular Organelles ◽

Cytoskeletal Elements ◽

Simultaneous Visualization

The microtubule (MT) cytoskeleton is necessary for many of the polarized functions of hepatocytes. Among the functions dependent on the MT-based cytoskeleton are polarized secretion of proteins, delivery of endocytosed material to lysosomes, and transcytosis of integral plasma membrane (PM) proteins. Although microtubules have been shown to be crucial to the establishment and maintenance of functional and structural polarization in the hepatocyte, little is known about the architecture of the hepatocyte MT cytoskeleton in vivo, particularly with regard to its relationship to PM domains and membranous organelles. Using an in situ extraction technique that preserves both microtubules and cellular membranes, we have developed a protocol for immunofluorescent co-localization of cytoskeletal elements and integral membrane proteins within 20 µm cryosections of fixed rat liver. Computer-aided 3D reconstruction of multi-spectral confocal microscope images was used to visualize the spatial relationships among the MT cytoskeleton, PM domains and intracellular organelles.

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Okra polysaccharides inhibit adhesion of Campylobacter jejuni to mucosa from poultry in situ but not in vivo within infection study

Planta Medica ◽

10.1055/s-2006-949869 ◽

2006 ◽

Vol 72 (11) ◽

Author(s):

A Hensel ◽

C Lengsfeld ◽

G Faller

Keyword(s):

Campylobacter Jejuni ◽

Infection Study

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Evaluation of Structure-Controlled Silk Fibroin Coatings for Orthopedic Infection and In-Situ Osteogenesis: In Vitro and In Vivo

SSRN Electronic Journal ◽

10.2139/ssrn.3600190 ◽

2020 ◽

Author(s):

Wenhao Zhou ◽

Teng Zhang ◽

Jianglong Yan ◽

QiYao Li ◽

Panpan Xiong ◽

...

Keyword(s):

Silk Fibroin ◽

Orthopedic Infection

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Phase Sensitive Biodegradable Polymer Based In situ Implant of Olanzapine for Depot Injectable Formulation: In vitro Release and In vivo Absorption in Rats

Current Pharmaceutical Analysis ◽

10.2174/1573412911666150408223837 ◽

2015 ◽

Vol 11 (4) ◽

pp. 286-291 ◽

Cited By ~ 1

Author(s):

Fahad Pervaiz ◽

Mahmood Ahmad ◽

Ghulam Murtaza

Keyword(s):

Biodegradable Polymer ◽

Injectable Formulation ◽

Phase Sensitive ◽

In Situ Implant

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Ferromagnetic soft catheter robots for minimally invasive bioprinting

Nature Communications ◽

10.1038/s41467-021-25386-w ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Cheng Zhou ◽

Youzhou Yang ◽

Jiaxin Wang ◽

Qingyang Wu ◽

Zhuozhi Gu ◽

...

Keyword(s):

Minimally Invasive ◽

The Body ◽

Magnetic Actuation ◽

Internal Organs ◽

Planar Surfaces ◽

Reinforced Polymer ◽

Direct Fabrication ◽

Digitally Controlled

AbstractIn vivo bioprinting has recently emerged as a direct fabrication technique to create artificial tissues and medical devices on target sites within the body, enabling advanced clinical strategies. However, existing in vivo bioprinting methods are often limited to applications near the skin or require open surgery for printing on internal organs. Here, we report a ferromagnetic soft catheter robot (FSCR) system capable of in situ computer-controlled bioprinting in a minimally invasive manner based on magnetic actuation. The FSCR is designed by dispersing ferromagnetic particles in a fiber-reinforced polymer matrix. This design results in stable ink extrusion and allows for printing various materials with different rheological properties and functionalities. A superimposed magnetic field drives the FSCR to achieve digitally controlled printing with high accuracy. We demonstrate printing multiple patterns on planar surfaces, and considering the non-planar surface of natural organs, we then develop an in situ printing strategy for curved surfaces and demonstrate minimally invasive in vivo bioprinting of hydrogels in a rat model. Our catheter robot will permit intelligent and minimally invasive bio-fabrication.

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Development of In Situ Self-Assembly Nanoparticles to Encapsulate Lopinavir and Ritonavir for Long-Acting Subcutaneous Injection

Pharmaceutics ◽

10.3390/pharmaceutics13060904 ◽

2021 ◽

Vol 13 (6) ◽

pp. 904

Author(s):

Irin Tanaudommongkon ◽

Asama Tanaudommongkon ◽

Xiaowei Dong

Keyword(s):

Sustained Release ◽

Trough Concentration ◽

Self Assembly ◽

Subcutaneous Injection ◽

Drug Loading ◽

Entrapment Efficiency ◽

Long Acting

Most antiretroviral medications for human immunodeficiency virus treatment and prevention require high levels of patient adherence, such that medications need to be administered daily without missing doses. Here, a long-acting subcutaneous injection of lopinavir (LPV) in combination with ritonavir (RTV) using in situ self-assembly nanoparticles (ISNPs) was developed to potentially overcome adherence barriers. The ISNP approach can improve the pharmacokinetic profiles of the drugs. The ISNPs were characterized in terms of particle size, drug entrapment efficiency, drug loading, in vitro release study, and in vivo pharmacokinetic study. LPV/RTV ISNPs were 167.8 nm in size, with a polydispersity index of less than 0.35. The entrapment efficiency was over 98% for both LPV and RTV, with drug loadings of 25% LPV and 6.3% RTV. A slow release rate of LPV was observed at about 20% on day 5, followed by a sustained release beyond 14 days. RTV released faster than LPV in the first 5 days and slower than LPV thereafter. LPV trough concentration remained above 160 ng/mL and RTV trough concentration was above 50 ng/mL after 6 days with one subcutaneous injection. Overall, the ISNP-based LPV/RTV injection showed sustained release profiles in both in vitro and in vivo studies.

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