In vivo glucoregulation and tissue-specific glucose uptake in female Akt substrate 160 kDa knockout rats.

07:00 EST 13th February 2020 | BioPortfolio

Summary of "In vivo glucoregulation and tissue-specific glucose uptake in female Akt substrate 160 kDa knockout rats."

The Rab GTPase activating protein known as Akt substrate of 160 kDa (AS160 or TBC1D4) regulates insulin-stimulated glucose uptake in skeletal muscle, the heart, and white adipose tissue (WAT). A novel rat AS160-knockout (AS160-KO) was created with CRISPR/Cas9 technology. Because female AS160-KO versus wild type (WT) rats had not been previously evaluated, the primary objective of this study was to compare female AS160-KO rats with WT controls for multiple, important metabolism-related endpoints. Body mass and composition, physical activity, and energy expenditure were not different between genotypes. AS160-KO versus WT rats were glucose intolerant based on an oral glucose tolerance test (P<0.001) and insulin resistant based on a hyperinsulinemic-euglycemic clamp (HEC; P<0.001). Tissue glucose uptake during the HEC of female AS160-KO versus WT rats was: 1) significantly lower in epitrochlearis (P<0.05) and extensor digitorum longus (EDL; P<0.01) muscles of AS160-KO compared to WT rats; 2) not different in soleus, gastrocnemius or WAT; and 3) ~3-fold greater in the heart (P<0.05). GLUT4 protein content was reduced in AS160-KO versus WT rats in the epitrochlearis (P<0.05), EDL (P<0.05), gastrocnemius (P<0.05), soleus (P<0.05), WAT (P<0.05), and the heart (P<0.005). Insulin-stimulated glucose uptake by isolated epitrochlearis and soleus muscles was lower (P<0.001) in AS160-KO versus WT rats. Akt phosphorylation of insulin-stimulated tissues was not different between the genotypes. A secondary objective was to probe processes that might account for the genotype-related increase in myocardial glucose uptake, including glucose transporter protein abundance (GLUT1, GLUT4, GLUT8, SGLT1), hexokinase II protein abundance, and stimulation of the AMP-activated protein kinase (AMPK) pathway. None of these parameters differed between genotypes. Metabolic phenotyping in the current study revealed AS160 deficiency produced a profound glucoregulatory phenotype in female AS160-KO rats that was strikingly similar to the results previously reported in male AS160-KO rats.


Journal Details

This article was published in the following journal.

Name: PloS one
ISSN: 1932-6203
Pages: e0223340


DeepDyve research library

PubMed Articles [26093 Associated PubMed Articles listed on BioPortfolio]

Primary Adipocytes as a Model for Insulin Sensitivity.

Obesity and its comorbidity insulin resistance lead to the development of chronic metabolic diseases, such as impaired fasted blood glucose and type 2 diabetes. Adipose tissue plays an important role ...

Hydrocarboxylic acid receptor 1 in BAT regulates glucose uptake in mice fed a high-fat diet.

Interscapular brown adipose tissue (BAT) has the capability to take up glucose from the circulation. Despite the important role of BAT in the control of glucose homeostasis, the metabolic fate and fun...

Direct effects of glucagon on glucose uptake and lipolysis in human adipocytes.

We aim to investigate the expression of the glucagon receptor (GCGR) in human adipose tissue, and the impact of glucagon in glucose uptake and lipolysis in human adipocytes. GCGR gene expression in hu...

Characterization of glucose uptake metabolism in visceral fat by 18 F-FDG PET/CT reflects inflammatory status in metabolic syndrome.

The inflammatory activity of visceral adipose tissue (VAT) is elevated in metabolic syndrome (MS), and associated with vulnerability to atherosclerosis. Inflammation can be assessed by glucose uptake ...

Further in vivo characterization of C-(+)-PHNO uptake into a retina-like region of interest in humans.

The neurotransmitter dopamine is present in the retina and is involved in several modulatory functions. Unlike in rodents, dopamine D receptors are expressed in the retina of humans. Recently, uptake ...

Clinical Trials [12824 Associated Clinical Trials listed on BioPortfolio]

Effect of Lactose, Fructose, Sucrose, Whey Protein, and Soy Protein on Substrate Absorption and Oxidation: a Pilot Study

Does the consumption of various combinations of mono and disaccharides (lactose, sucrose and fructose) and protein isolates (whey or soy) result in altered substrate absorption, substrate ...

Effects of Intranasal Insulin Administration on Tissue Specific Insulin Sensitivity

Recent research has suggested that intranasally administered insulin can reach the brain quickly without passing through circulation and evoke increased insulin sensitivity and tissue gluc...

The Effect of Nutrient Intake on the Microbiome, Weight, and Glucoregulation (NI-MWG)

The purpose of this study is to investigate a persons dietary intake and its effect on the gut microbiome and the association of those two variables on weight and glucoregulation. Specific...

Lipolytic Effects of GH in Hypopituitary Patients in Vivo

Growth hormone (GH) is essential for longitudinal bone growth and somatic development. These protein anabolic effects require sufficient nutritional supply. During fasting and caloric rest...

iKnife REIMS Project

There are currently no widely accepted methods which provide real time in vivo, in situ tissue diagnostics within the operating theatre environment. This project proposes that the oncolog...

Medical and Biotech [MESH] Definitions

A glucose transport protein found in mature MUSCLE CELLS and ADIPOCYTES. It promotes transport of glucose from the BLOOD into target TISSUES. The inactive form of the protein is localized in CYTOPLASMIC VESICLES. In response to INSULIN, it is translocated to the PLASMA MEMBRANE where it facilitates glucose uptake.

A group of enzymes that catalyzes the conversion of ATP and D-glucose to ADP and D-glucose 6-phosphate. They are found in invertebrates and microorganisms, and are highly specific for glucose. (Enzyme Nomenclature, 1992) EC

A non-metabolizable glucose analogue that is not phosphorylated by hexokinase. 3-O-Methylglucose is used as a marker to assess glucose transport by evaluating its uptake within various cells and organ systems. (J Neurochem 1993;60(4):1498-504)

An enzyme of the oxidoreductase class that catalyzes the conversion of beta-D-glucose and oxygen to D-glucono-1,5-lactone and peroxide. It is a flavoprotein, highly specific for beta-D-glucose. The enzyme is produced by Penicillium notatum and other fungi and has antibacterial activity in the presence of glucose and oxygen. It is used to estimate glucose concentration in blood or urine samples through the formation of colored dyes by the hydrogen peroxide produced in the reaction. (From Enzyme Nomenclature, 1992) EC

A 12-kDa cysteine-rich polypeptide hormone secreted by FAT CELLS in the ADIPOSE TISSUE. It is the founding member of the resistin-like molecule (RELM) hormone family. Resistin suppresses the ability of INSULIN to stimulate cellular GLUCOSE uptake.

Quick Search

DeepDyve research library

Relevant Topics

Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...

Endocrine Disorders
Endocrine disorders are grouped into two categories: hormone imbalance - when a gland produces too much or too little of an endocrine hormone development of lesions (such as nodules or tumors) in the endocrine system, which may or may not affect...

Arthritis Fibromyalgia Gout Lupus Rheumatic Rheumatology is the medical specialty concerned with the diagnosis and management of disease involving joints, tendons, muscles, ligaments and associated structures (Oxford Medical Diction...

Searches Linking to this Article