Muscle-Specific Ablation of Glucose Transporter 1 (GLUT1) Does Not Impair Basal or Overload-Stimulated Skeletal Muscle Glucose Uptake.

Glucose transporter 1 (GLUT1) is believed to solely mediate basal (insulin-independent) glucose uptake in skeletal muscle; yet recent work has demonstrated that mechanical overload, a model of resistance exercise training, increases muscle GLUT1 levels. The primary objective of this study was to determine if GLUT1 is necessary for basal or overload-stimulated muscle glucose uptake. Muscle-specific GLUT1 knockout (mGLUT1KO) mice were generated and examined for changes in body weight, body composition, metabolism, systemic glucose regulation, muscle glucose transporters, and muscle [H]-2-deoxyglucose uptake ± the GLUT1 inhibitor BAY-876.

GLUT4 On the move.

Insulin rapidly stimulates GLUT4 translocation and glucose transport in fat and muscle cells. Signals from the occupied insulin receptor are translated into downstream signalling changes in serine/threonine kinases within timescales of seconds, and this is followed by delivery and accumulation of the glucose transporter GLUT4 at the plasma membrane. Kinetic studies have led to realisation that there are distinct phases of this stimulation by insulin.

Structure, function and regulation of mammalian glucose transporters of the SLC2 family.

The SLC2 genes code for a family of GLUT proteins that are part of the major facilitator superfamily (MFS) of membrane transporters. Crystal structures have recently revealed how the unique protein fold of these proteins enables the catalysis of transport. The proteins have 12 transmembrane spans built from a replicated trimer substructure.

Beta Decay of Molecular Tritium.

The beta decay of tritium in the form of molecular T_{2} is the basis of sensitive experiments to measure neutrino mass. The final-state electronic, vibrational, and rotational excitations modify the beta spectrum significantly and are obtained from theory. We report measurements of the branching ratios to specific ionization states for the isotopolog HT.

Chemical biology probes of mammalian GLUT structure and function.

The structure and function of glucose transporters of the mammalian GLUT family of proteins has been studied over many decades, and the proteins have fascinated numerous research groups over this time. This interest is related to the importance of the GLUTs as archetypical membrane transport facilitators, as key limiters of the supply of glucose to cell metabolism, as targets of cell insulin and exercise signalling and of regulated membrane traffic, and as potential drug targets to combat cancer and metabolic diseases such as type 2 diabetes and obesity. This review focusses on the use of chemical biology approaches and sugar analogue probes to study these important proteins.

An overview of extant conifer evolution from the perspective of the fossil record.

Premise Of The Study: Conifers are an important living seed plant lineage with an extensive fossil record spanning more than 300 million years. The group therefore provides an excellent opportunity to explore congruence and conflict between dated molecular phylogenies and the fossil record.

Methods: We surveyed the current state of knowledge in conifer phylogenetics to present a new time-calibrated molecular tree that samples ~90% of extant species diversity.

Police and mental health responses to mental health crisis in the Waikato region of New Zealand.

New Zealand police report a high level of involvement with people in mental health crisis, something that has been reported in the international literature in recent decades. Involvement of police represents a coercive pathway to care and is likely to be associated with use of force. The aim of this study was to investigate the clinical, legal, and social characteristics of individuals subject to police response in the Waikato region of New Zealand.

Meaningful use's benefits and burdens for US family physicians.

Objective: The federal meaningful use (MU) program was aimed at improving adoption and use of electronic health records, but practicing physicians have criticized it. This study was aimed at quantifying the benefits (ie, usefulness) and burdens (ie, workload) of the MU program for practicing family physicians.

Materials And Methods: An interdisciplinary national panel of experts (physicians and engineers) identified the work associated with MU criteria during patient encounters.

Identification of Insulin-Activated Rab Proteins in Adipose Cells Using Bio-ATB-GTP Photolabeling Technique.

We have recently developed a photolabeling method to identify GTP-loaded Rab proteins. The new biotinylated GTP analogue (Bio-ATB-GTP) binds to GTP-binding proteins and after a UV irradiation a covalent bond is formed between the protein and the photoreactive diazirine group on the photolabel. The tagged protein can then be isolated and detected using the classic biotin-streptavidin interaction.

Molecular adaptations of adipose tissue to 6 weeks of morning fasting vs. daily breakfast consumption in lean and obese adults.

Key Points: In lean individuals, 6 weeks of extended morning fasting increases the expression of genes involved in lipid turnover (ACADM) and insulin signalling (IRS2) in subcutaneous abdominal adipose tissue. In obese individuals, 6 weeks of extended morning fasting increases IRS2 expression in subcutaneous abdominal adipose tissue. The content and activation status of key proteins involved in insulin signalling and glucose transport (GLUT4, Akt1 and Akt2) were unaffected by extended morning fasting.

Thermal stability, storage and release of proteins with tailored fit in silica.

Biological substances based on proteins, including vaccines, antibodies, and enzymes, typically degrade at room temperature over time due to denaturation, as proteins unfold with loss of secondary and tertiary structure. Their storage and distribution therefore relies on a "cold chain" of continuous refrigeration; this is costly and not always effective, as any break in the chain leads to rapid loss of effectiveness and potency. Efforts have been made to make vaccines thermally stable using treatments including freeze-drying (lyophilisation), biomineralisation, and encapsulation in sugar glass and organic polymers.

Highly Potent and Isoform Selective Dual Site Binding Tankyrase/Wnt Signaling Inhibitors That Increase Cellular Glucose Uptake and Have Antiproliferative Activity.

Compounds 13 and 14 were evaluated against 11 PARP isoforms to reveal that both 13 and 14 were more potent and isoform selective toward inhibiting tankyrases (TNKSs) than the "standard" inhibitor 1 (XAV939), i.e., IC = 100 pM vs TNKS2 and IC = 6.

Rab28 is a TBC1D1/TBC1D4 substrate involved in GLUT4 trafficking.

The Rab-GTPase-activating proteins (GAPs) TBC1D1 and TBC1D4 play important roles in the insulin-stimulated translocation of the glucose transporter GLUT4 from intracellular vesicles to the plasma membrane in muscle cells and adipocytes. We identified Rab28 as a substrate for the GAP domains of both TBC1D1 and TBC1D4 in vitro. Rab28 is expressed in adipose cells and skeletal muscle, and its GTP-binding state is acutely regulated by insulin.

The causal role of breakfast in energy balance and health: a randomized controlled trial in obese adults.

Background: The causal nature of associations between breakfast and health remain unclear in obese individuals.

Objective: We sought to conduct a randomized controlled trial to examine causal links between breakfast habits and components of energy balance in free-living obese humans.

Design: The Bath Breakfast Project is a randomized controlled trial with repeated measures at baseline and follow-up among a cohort in South West England aged 21-60 y with dual-energy X-ray absorptiometry-derived fat mass indexes of ≥13 kg/m(2) for women (n = 15) and ≥9 kg/m(2) for men (n = 8).

The myth of standardized workflow in primary care.

Objective: Primary care efficiency and quality are essential for the nation's health. The demands on primary care physicians (PCPs) are increasing as healthcare becomes more complex. A more complete understanding of PCP workflow variation is needed to guide future healthcare redesigns.

Proteomic Analysis of GLUT4 Storage Vesicles Reveals Tumor Suppressor Candidate 5 (TUSC5) as a Novel Regulator of Insulin Action in Adipocytes.

Insulin signaling augments glucose transport by regulating glucose transporter 4 (GLUT4) trafficking from specialized intracellular compartments, termed GLUT4 storage vesicles (GSVs), to the plasma membrane. Proteomic analysis of GSVs by mass spectrometry revealed enrichment of 59 proteins in these vesicles. We measured reduced abundance of 23 of these proteins following insulin stimulation and assigned these as high confidence GSV proteins.

Physiological and molecular responses to an acute bout of reduced-exertion high-intensity interval training (REHIT).

Purpose: We have previously shown that 6 weeks of reduced-exertion high-intensity interval training (REHIT) improves VO2max in sedentary men and women and insulin sensitivity in men. Here, we present two studies examining the acute physiological and molecular responses to REHIT.

Methods: In Study 1, five men and six women (age: 26 ± 7 year, BMI: 23 ± 3 kg m(-2), VO2max: 51 ± 11 ml kg(-1) min(-1)) performed a single 10-min REHIT cycling session (60 W and two 20-s 'all-out' sprints), with vastus lateralis biopsies taken before and 0, 30, and 180 min post-exercise for analysis of glycogen content, phosphorylation of AMPK, p38 MAPK and ACC, and gene expression of PGC1α and GLUT4.

Insulin regulates Rab3-Noc2 complex dissociation to promote GLUT4 translocation in rat adipocytes.

Aims/hypothesis: The glucose transporter GLUT4 is present mainly in insulin-responsive tissues of fat, heart and skeletal muscle and is translocated from intracellular membrane compartments to the plasma membrane (PM) upon insulin stimulation. The transit of GLUT4 to the PM is known to be dependent on a series of Rab proteins. However, the extent to which the activity of these Rabs is regulated by the action of insulin action is still unknown.

“Deletion of both Rab-GTPase–activating proteins TBC1D1 and TBC1D4 in mice eliminates insulin- and AICAR-stimulated glucose transport [corrected].

The Rab-GTPase–activating proteins TBC1D1 and TBC1D4 (AS160) were previously shown to regulate GLUT4 translocation in response to activation of AKT and AMP-dependent kinase [corrected]. However, knockout mice lacking either Tbc1d1 or Tbc1d4 displayed only partially impaired insulin-stimulated glucose uptake in fat and muscle tissue. The aim of this study was to determine the impact of the combined inactivation of Tbc1d1 and Tbc1d4 on glucose metabolism in double-deficient (D1/4KO) mice.

The causal role of breakfast in energy balance and health: a randomized controlled trial in lean adults.

Background: Popular beliefs that breakfast is the most important meal of the day are grounded in cross-sectional observations that link breakfast to health, the causal nature of which remains to be explored under real-life conditions.

Objective: The aim was to conduct a randomized controlled trial examining causal links between breakfast habits and all components of energy balance in free-living humans.

Design: The Bath Breakfast Project is a randomized controlled trial with repeated-measures at baseline and follow-up in a cohort in southwest England aged 21-60 y with dual-energy X-ray absorptiometry-derived fat mass indexes ≤11 kg/m² in women (n = 21) and ≤7.

Medium- and long-term storage of the Pycnanthemum (mountain mint) germplasm collection.

The United States of America collection of mountain mint (Pycnanthemum Michx.) is held at the USDA-ARS National Clonal Germplasm Repository (NCGR) in Corvallis, Oregon as seed, potted plants and tissue cultures and a long-term storage collection is preserved at the USDA-ARS National Center for Genetic Resources Preservation (NCGRP) in Fort Collins, Colorado. The clonal collection is comprised of 34 accessions as potted plants that are duplicated with 31 accessions stored as in vitro cultures at 4 degrees C in tissue culture bags for medium-term storage at NCGR and as cryopreserved shoot tips in liquid nitrogen at NCGRP for long-term storage.

FGT-1 is the major glucose transporter in C. elegans and is central to aging pathways.

Caenorhabditis elegans is widely used as a model for investigation of the relationships between aging, nutrient restriction and signalling via the DAF-2 (abnormal dauer formation 2) receptor for insulin-like peptides and AGE-1 [ageing alteration 1; orthologue of PI3K (phosphoinositide 3-kinase)], but the identity of the glucose transporters that may link these processes is unknown. We unexpectedly find that of the eight putative GLUT (glucose transporter)-like genes only the two splice variants of one gene have a glucose transport function in an oocyte expression system. We have named this gene fgt-1 (facilitated glucose transporter, isoform 1).