Glucose Transporter Type 4

Publication Title: 
BioFactors (Oxford, England)

The thiazolidinedione (TZDs) class of drugs are very effective for the treatment of type 2 diabetes mellitus (T2DM). But due to the adverse effects of synthetic TZDs, their use is strictly regulated. The therapeutic actions of TZDs are mediated via modulation of peroxisome proliferator-activated receptor gamma (PPAR?). Naturally occurring PPAR? modulators are more desirable as they lack the serious adverse effects caused by TZDs. This has prompted the exploitation of medicinal plants used in traditional medicine, for their potential PPAR? activity.

Author(s): 
Shyni, Gangadharan Leela
Kavitha, Sasidharan
Indu, Sasidharan
Arya, Anil Das
Anusree, Sasidharan Suseela
Vineetha, Vadavanath Prabhakaran
Vandana, Sankar
Sundaresan, Andikannu
Raghu, Kozhiparambil Gopalan
Publication Title: 
Experimental Gerontology

Chronic caloric restriction (CR) has been demonstrated to increase longevity in lower species and studies are ongoing to evaluate its effect in higher species. A consistent metabolic feature of CR is improved insulin sensitivity and lowered lifetime glycemia, yet the mechanism responsible is currently unknown. However, the membrane's physiochemical properties, as determined by phospholipid composition, have been related to insulin action in animal and human studies and CR has been reported to alter membrane lipid content.

Author(s): 
Cefalu, W. T.
Wang, Z. Q.
Bell-Farrow, A. D.
Terry, J. G.
Sonntag, W.
Waite, M.
Parks, J.
Publication Title: 
Prostaglandins, Leukotrienes, and Essential Fatty Acids

GLUT-4 (glucose transporter) receptor, tumor necrosis factor-alpha (TNF-alpha), interleukins-6 (IL-6), daf-genes and PPARs (peroxisomal proliferation activator receptors) play a role in the development of insulin resistance syndrome and associated conditions. But, the exact interaction between these molecules/factors and the mechanism(s) by which they produce insulin resistance syndrome is not clear.

Author(s): 
Das, Undurti N.
Publication Title: 
Journal of Diabetes

BACKGROUND: Cinnamomum cassia (Family: Lauraceae) is an Ayurvedic medicinal plant used traditionally for the treatment of a number of diseases, including diabetes. The hypoglycemic effect of this plant has been established in vivo. However, the effects of cinnamic acid, isolated from C. cassia, on the insulin signaling cascade in an in vitro model have not been elucidated. Hence, the aim of the present study was to evaluate the anti-diabetic effect of cinnamic acid on glucose transport by L6 myotubes.

Author(s): 
Lakshmi, Baddireddi Subhadra
Sujatha, Sundaresan
Anand, Singaravelu
Sangeetha, Kadapakkam Nandhabalan
Narayanan, Rangarajan Badri
Katiyar, Chandrakanth
Kanaujia, Anil
Duggar, Rajeev
Singh, Yogendra
Srinivas, Konasubrahmanya
Bansal, Vinay
Sarin, Simi
Tandon, Ruchi
Sharma, Suchitra
Singh, Suchita
Publication Title: 
The Journal of Biological Chemistry

Cell culture work suggests that signaling to polymerize cortical filamentous actin (F-actin) represents a required pathway for the optimal redistribution of the insulin-responsive glucose transporter, GLUT4, to the plasma membrane. Recent in vitro study further suggests that the actin-regulatory neural Wiskott-Aldrich syndrome protein (N-WASP) mediates the effect of insulin on the actin filament network. Here we tested whether similar cytoskeletal mechanics are essential for insulin-regulated glucose transport in isolated rat epitrochlearis skeletal muscle.

Author(s): 
Brozinick, Joseph T.
Hawkins, Eric D.
Strawbridge, Andrew B.
Elmendorf, Jeffrey S.
Publication Title: 
The Journal of Biological Chemistry

Muscle and fat cells develop insulin resistance when cultured under hyperinsulinemic conditions for sustained periods. Recent data indicate that early insulin signaling defects do not fully account for the loss of insulin action. Given that cortical filamentous actin (F-actin) represents an essential aspect of insulin regulated glucose transport, we tested to see whether cortical F-actin structure was compromised during chronic insulin treatment.

Author(s): 
Chen, Guoli
Raman, Priya
Bhonagiri, Padma
Strawbridge, Andrew B.
Pattar, Guruprasad R.
Elmendorf, Jeffrey S.
Publication Title: 
Journal of Cellular Biochemistry

Endothelin-1 (ET-1) disrupts insulin-regulated glucose transporter GLUT4 trafficking. Since the negative consequence of chronic ET-1 exposure appears to be independent of signal disturbance along the insulin receptor substrate-1/phosphatidylinositol (PI) 3-kinase (PI3K)/Akt-2 pathway of insulin action, we tested if ET-1 altered GLUT4 regulation engaged by osmotic shock, a PI3K-independent stimulus that mimics insulin action. Regulation of GLUT4 by hyperosmotic stress was impaired by ET-1.

Author(s): 
Strawbridge, Andrew B.
Elmendorf, Jeffrey S.
Publication Title: 
American Journal of Physiology. Cell Physiology

Study has demonstrated an essential role of cortical filamentous actin (F-actin) in insulin-regulated glucose uptake by skeletal muscle. Here, we tested whether perturbations in F-actin contributed to impaired insulin responsiveness provoked by hyperinsulinemia. In L6 myotubes stably expressing GLUT4 that carries an exofacial myc-epitope tag, acute insulin stimulation (20 min, 100 nM) increased GLUT4myc translocation and glucose uptake by approximately 2-fold.

Author(s): 
McCarthy, Alicia M.
Spisak, Kristen O.
Brozinick, Joseph T.
Elmendorf, Jeffrey S.
Publication Title: 
Mutation Research

Since trivalent chromium (Cr(3+)) enhances glucose metabolism, interest in the use of Cr(3+)as a therapy for type 2 diabetes has grown in the mainstream medical community. Moreover, accumulating evidence suggests that Cr(3+) may also benefit cardiovascular disease (CVD) and atypical depression. We have found that cholesterol, a lipid implicated in both CVD and neurodegenerative disorders, also influences cellular glucose uptake. A recent study in our laboratory shows that exposure of 3T3-L1 adipocytes to chromium picolinate (CrPic, 10 nM) induces a loss of plasma membrane cholesterol.

Author(s): 
Pattar, Guruprasad R.
Tackett, Lixuan
Liu, Ping
Elmendorf, Jeffrey S.
Publication Title: 
Molecular Endocrinology (Baltimore, Md.)

Previously, we found that a loss of plasma membrane (PM) phosphatidylinositol 4,5-bisphosphate (PIP2)-regulated filamentous actin (F-actin) structure contributes to insulin-induced insulin resistance. Interestingly, we also demonstrated that chromium picolinate (CrPic), a dietary supplement thought to improve glycemic status in insulin-resistant individuals, augments insulin-regulated glucose transport in insulin-sensitive 3T3-L1 adipocytes by lowering PM cholesterol.

Author(s): 
Horvath, Emily M.
Tackett, Lixuan
McCarthy, Alicia M.
Raman, Priya
Brozinick, Joseph T.
Elmendorf, Jeffrey S.

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