Insulin stimulates glucose uptake into the target tissues of fat and muscle by recruiting or translocating Glut4 glucose transport proteins to their functional location at the cell surface. In the basal state, Glut4 is sequestered intracellularly in several vesicular compartments, one of which has come to be known as Glut4 ...

Glucose is the main metabolic fuel in mammalian cells. Glucose entry into cells is facilitated by a family of ubiquitously expressed glucose transporter proteins. Typically, glucose transporters are localized on the plasma membrane. One notable exception is the glucose transporter isoform 4 (Glut4), which is specifically expressed in insulin sensitive ...

Postprandial blood glucose homeostasis is regulated by an insulin-stimulated increase in glucose transport into muscle and fat tissues via glucose transporter isoform 4 (GLUT4). In the basal state, this constitutively recycling membrane protein predominantly resides intracellularly. In order to achieve the insulin-stimulated increase in glucose flux, GLUT4 increases its cell ...

Insulin induces translocation of the glucose transporter GLUT4 from intracellular storage compartment to the plasma membrane via complex mechanisms that require intact cytoskeletal networks. In cultured adipocytes, conventional kinesin motor proteins have been proposed to mediate GLUT4 movements on microtubules. It remains, however, unclear whether kinesin motor system plays a ...

BACKGROUND: Insulin stimulates glucose uptake by adipocytes through increasing translocation of the glucose transporter GLUT4 from an intracellular compartment to the plasma membrane. Fusion of GLUT4-containing vesicles at the cell surface is thought to involve phospholipase D activity, generating the signalling lipid phosphatidic acid, although the mechanism of action is ...

The phosphotransferase system (PTS) is the sugar transportation machinery that is widely distributed in prokaryotes and is critical for enhanced production of useful metabolites. To increase the glucose uptake rate, we propose a rational strategy for designing the molecular architecture of the Escherichia coli glucose PTS by using a computer-aided ...

BACKGROUND: Focal Adhesion Kinase (FAK) is recently reported to regulate insulin resistance by regulating glucose uptake in C2C12 skeletal muscle cells. However, the underlying mechanism for FAK-mediated glucose transporter-4 translocation (Glut-4), responsible for glucose uptake, remains unknown. Recently actin remodeling was reported to be essential for Glut-4 translocation. Therefore, we ...

The loss of a glutamic acid residue in the AAA-ATPase (ATPases associated with diverse cellular activities) torsinA is responsible for most cases of early onset autosomal dominant primary dystonia. In this study, we found that snapin, which binds SNAP-25 (synaptosome-associated protein of 25,000 Da) and enhances the association of the ...

In cardiac and skeletal muscles, insulin regulates the uptake of long-chain fatty acid (LCFA) via the putative LCFA transporter CD36. Biochemical studies propose an insulin-induced translocation of CD36 from intracellular pools to the plasma membrane (PM), similar to glucose transporter 4 (GLUT4) translocation. To characterize insulin-induced CD36 translocation in intact ...

Genistein is a phytoestrogen exerting numerous biological effects. Its direct influence on adipocyte metabolism and leptin secretion was previously demonstrated. This study aimed to determine whether genistein antagonizes the antilipolytic action of insulin in rat adipocytes. Freshly isolated adipose cells were incubated for 90 min with epinephrine, epinephrine with insulin ...

Insulin-stimulated GLUT4 translocation to the plasma membrane constitutes a key process for blood glucose control. However, convenient and robust assays to monitor this dynamic process in real time are lacking, which hinders current progress toward elucidation of the underlying molecular events as well as screens for drugs targeting this particular ...

In order to characterize the potential causative effects of interleukin-18 (IL-18) on insulin resistance, we measured glucose uptake in 3T3-L1 adipocytes treated with mouse recombinant IL-18. IL-18 surprisingly enhanced, rather than reduced insulin-mediated glucose uptake in adipocytes. Moreover IL-18 could counteract the glucose uptake suppression caused by tumor necrosis factor ...

The leaves of Lagerstroemia speciosa (Lythraceae), a Southeast Asian tree more commonly known as banaba, have been traditionally consumed in various forms by Philippinos for treatment of diabetes and kidney related diseases. In the 1990s, the popularity of this herbal medicine began to attract the attention of scientists worldwide. Since ...

The translocation of GLUT4 to the plasma membrane underlies the ability of insulin to stimulate glucose uptake, an event that involves the activation of protein kinase B, several members of the Rab family of GTP-binding proteins and the phosphorylation of the Rab GTPase-activating protein AS160. Here, we explored the regulation ...

It has recently been known that berberine, an alkaloid of medicinal plants, has anti-hyperglycemic effects. To explore the mechanism underlying this effect, we used 3T3-L1 adipocytes for analyzing the signaling pathways that contribute to glucose transport. Treatment of berberine to 3T3-L1 adipocytes for 6 h enhanced basal glucose uptake both ...

OBJECTIVE: Insulin stimulates glucose transport in skeletal muscle by GLUT4 translocation from intracellular compartments to sarcolemma and t-tubules. We studied in living animals the recruitment of GLUT4 vesicles in more detail than previously done and, for the first time, analyzed the steady-state recycling and subsequent re-internalization of GLUT4 on an ...

Berberine, a botanical alkaloid used to control blood glucose in type 2 diabetes in China, has recently been reported to activate AMPK. However, it is not clear how AMPK is activated by berberine. In this study, activity and action mechanism of berberine were investigated in vivo and in vitro. In ...

In adipocytes, insulin triggers the redistribution of Glut4 from intracellular compartments to the plasma membrane. Two models have been proposed to explain the effect of insulin on Glut4 localization. In the first, termed dynamic exchange, Glut4 continually cycles between the plasma membrane and intracellular compartments in basal cells, and the ...

AIM/HYPOTHESIS: The distinct metabolic properties of visceral and subcutaneous adipocytes may be due to inherent characteristics of the cells that are resident in each fat depot. To test this hypothesis, human adipocytes were differentiated in vitro from precursor stromal cells obtained from visceral and subcutaneous fat depots and analysed for ...

BACKGROUND: AMP-activated protein kinase (AMPK) activation plays an essential role in glucose metabolism of the heart. This study aimed at investigating whether AMPK was involved in glucose transporter-4 (GLUT-4) translocation induced by azide-induced chemical hypoxia in primary cultured neonatal rat cardiomyocytes. METHODS: With or without adenine 9-beta-D-arabinofuranoside (ara A, AMPK ...

The cells of the marine bacterium strain C-21, which is phylogenetically closely related to Arenibacter troitsensis, accumulate iodine in the presence of glucose and iodide (I-). In this study, the detailed mechanism of iodine uptake by C-21 was determined using a radioactive iodide tracer, 125I-. In addition to glucose, oxygen ...

Lysophosphatidic acid (LPA) is known to have diverse cellular effects, but although LPA is present in many biological fluids, including blood, its effects on glucose metabolism have not been elucidated. In this study, we investigated whether LPA stimulation is related to glucose regulation. LPA was found to enhance glucose uptake ...

Insulin resistance plays a major role in the pathogenesis of type 2 diabetes. Insulin regulates blood glucose levels primarily by promoting glucose uptake from the blood into multiple tissues and by suppressing glucose production from the liver. The glucose transporter, GLUT4, mediates insulin-stimulated glucose uptake in muscle and adipose tissue. ...

The transportation of glucose, the primary energy source of all eukaryotic cells, from the bloodstream to the cells is catalyzed by a family of glucose transporters (GLUTs), among which GLUT4 is insulin stimulated and regulated. To study the insulinstimulated glucose transport, we analyze the hybrid metabolic and signaling pathway models ...

Adipocytes are primary targets for insulin control of metabolism. The activated insulin receptor phosphorylates insulin receptor substrate-1 (IRS1), which acts as a docking protein for downstream signal mediators. In the absence of insulin stimulation, IRS1 in rat adipocytes is intracellular but in human adipocytes IRS1 is constitutively targeted to the ...

L6 skeletal muscle myoblasts stably overexpressing glucose transporter GLUT1 or GLUT4 with exofacial myc-epitope tags were characterized for their response to insulin. In clonally selected cultures, 2-deoxyglucose uptake into L6-GLUT1myc myoblasts and myotubes was linear within the time of study. In L6-GLUT1myc and L6-GLUT4myc myoblasts, 100 nmol/L insulin treatment increased ...

Apelin, a novel peptide with significant cardioactive properties, is upregulated by insulin in adipocytes. However, the mechanism by which insulin promotes apelin production is unknown. Hypoxia-inducible factor-1 (HIF-1), a heterodimeric transcription factor involved in the angiogenic and metabolic responses to tissue hypoxia, has been shown to be activated by insulin ...

OBJECTIVE: We sought to determine the role of adipocyte death in obesity-induced adipose tissue (AT) inflammation and obesity complications. RESEARCH DESIGN AND METHODS: Male C57BL/6 mice were fed a high-fat diet for 20 weeks to induce obesity. Every 4 weeks, insulin resistance was assessed by intraperitoneal insulin tolerance tests, and ...

In secretory cells, osmotic swelling of secretory granules is proposed to be an intermediate step in exocytic fusion of the granules with the plasma membrane. For osmotic swelling of the granule, a H (+) gradient generated by vacuolar-type H (+) -ATPase (V-ATPase) may be a driving force for accumulation of ...

Lipid peroxidation induced by reactive oxygen species might modify circulating biomolecules because of the formation of alpha,beta-unsaturated or dicarbonylic aldehydes. In order to investigate the interaction between a lipoperoxidation product, acrolein, and a circulating protein, insulin, the acrolein-insulin adduct was obtained. To characterize the adduct, gel filtration chromatography, sodium dodecylsulfate-polyacrylamide ...

PURPOSE: Mitochondrial dysfunction has been attributed a critical role in the etiology and pathogenesis of numerous diseases, and is manifested by alterations of the organelle's membrane potential (Deltapsi(m)). This suggests that Deltapsi(m) measurement can be highly useful for diagnostic purposes. In the current study, we characterized the capability of the ...

C-reactive protein (CRP) is a powerful predictor for coronary heart diseases. Recent study has revealed that adipocytes can produce CRP. Peroxisome proliferator-activated receptor (PPAR) gamma, an important nuclear transcriptional factor, can be predominately detected in adipocytes and exert several biological properties, including antiinflammatory effects. The authors investigated the effects of ...

Extracts of the Canadian lowbush blueberry (Vaccinium angustifolium Ait.) have recently been demonstrated to possess significant antidiabetic potential, in accordance with the traditional use of this plant as an antidiabetic natural health product. Fermentation of blueberry juice with the Serratia vaccinii bacterium is known to modify the phenolic content and ...

Insulin stimulates glucose transport in muscle and adipose tissue by producing translocation of the glucose transporter Glut4. The exocyst, an evolutionarily conserved vesicle tethering complex, is crucial for targeting Glut4 to the plasma membrane. Here we report that insulin regulates this process via the G protein RalA, which is present ...

Caveolae and non-caveolar lipid rafts are two types of membrane lipid microdomains that play important roles in insulin-stimulated glucose uptake in adipocytes. In order to ascertain their specific functions in this process, caveolae were ablated by caveolin-1 RNA interference. In Cav-1 RNAi adipocytes, neither insulin-stimulated glucose uptake nor Glut-4 (glucose ...

Newly synthesized glucose transporter 4 (GLUT4) enters into the insulin-responsive storage compartment in a process that is Golgi-localized gamma-ear-containing Arf-binding protein (GGA) dependent, whereas insulin-stimulated translocation is regulated by Akt substrate of 160 kDa (AS160). In the present study, using a variety of GLUT4/GLUT1 chimeras, we have analyzed the specific ...

In mammals, glucose transporter (GLUT)-4 plays an important role in glucose homeostasis mediating insulin action to increase glucose uptake in insulin-responsive tissues. In the basal state, GLUT4 is located in intracellular compartments and upon insulin stimulation is recruited to the plasma membrane, allowing glucose entry into the cell. Compared with ...

Insulin regulates blood glucose by promoting uptake by fat and muscle, and inhibiting production by liver. Insulin-stimulated glucose uptake is mediated by GLUT4, which translocates from an intracellular compartment to the plasma membrane. GLUT4 traffic and insulin secretion both rely on calcium-dependent, regulated exocytosis. Deletion of the voltage-gated potassium channel ...

Insulin-regulated aminopeptidase (IRAP) is a membrane aminopeptidase and is homologous to the placental leucine aminopeptidase, P-LAP. IRAP has a wide distribution but has been best characterized in adipocytes and myocytes. In these cells, IRAP colocalizes with the glucose transporter GLUT4 to intracellular vesicles and, like GLUT4, translocates from these vesicles ...

Isoprenaline, acting at beta-adrenoceptors (ARs), enhances memory formation in single trial discriminated avoidance learning in day-old chicks by mechanisms involving alterations in glucose and glycogen metabolism. Earlier studies of memory consolidation in chicks indicated that beta3-ARs enhanced memory by increasing glucose uptake, whereas beta2-ARs enhance memory by increasing glycogenolysis. This ...

Vanadium is a well known anti-diabetic agent which mimics most of the actions of insulin on mature adipocytes. We report here the effect of vanadium on proliferation and differentiation of 3T3-L1 preadipocytes. Like insulin, vanadium treatment leads to increased proliferation as evidenced by H(3)thymidine uptake studies and differentiation of 3T3-L1 ...

Glucose transporter 4 (GLUT4) is the major insulin-regulated glucose transporter expressed mainly in muscle and adipose tissue. GLUT4 is stored in a poorly characterized intracellular vesicular compartment and translocates to the cell surface in response to insulin stimulation resulting in an increased glucose uptake. This process is essential for the ...

Obesity is an alarming primary health problem and is an independent risk factor for type II diabetes, cardiovascular diseases, and hypertension. Although the pathologic mechanisms linking obesity with these co-morbidities are most likely multifactorial, increasing evidence indicates that altered secretion of adipose-derived signaling molecules (adipokines; e.g. adiponectin, leptin, and tumor ...

Actin remodeling plays a crucial role in insulin-induced translocation of glucose transporter 4 (GLUT4) from the cytoplasm to the plasma membrane and subsequent glucose transport. Protein kinase C (PKC) zeta has been implicated in this translocation process, although the exact mechanism remains unknown. In this study, we investigated the effect ...

Insulin-stimulated GLUT4 recruitment to the plasma membrane is impaired in insulin resistance. We recently reported that a cell permeable phosphoinositide-binding peptide induces GLUT4 recruitment as potently as insulin, but does not activate GLUT4 to initiate glucose uptake. Here we investigated whether the peptide-induced GLUT4 recruitment is intact in insulin resistance. ...

The hepatic clearance of amyloid beta-peptide (1-40) [Abeta(1-40)] from plasma, which is largely mediated by low-density lipoprotein receptor-related protein (LRP-1), is suggested to play a role in preventing Abeta(1-40) accumulation in the brain. Epidemiological investigations suggest a high incidence of cerebral Abeta deposition in insulin-resistant type II diabetes mellitus. The ...

Insulin regulates circulating glucose levels by suppressing hepatic glucose production and increasing glucose transport into muscle and adipose tissues. Defects in these processes are associated with elevated vascular glucose levels and can lead to increased risk for the development of Type 2 diabetes mellitus and its associated disease complications. At ...

Calpain-10 was first identified through a genome scan seeking to identify diabetes predisposition genes. Both genetic and functional data has since indicated that calpain-10 has an important role in insulin resistance and intermediate phenotypes, including those associated with adipocytes and skeletal muscle. Evidence presented in this issue by Brown, Yeaman, ...

The differentiation-inducing factor-1 (DIF-1) is a signal molecule that induces stalk cell formation in the cellular slime mold Dictyostelium discoideum, while DIF-1 and its analogs have been shown to possess antiproliferative activity in vitro in mammalian tumor cells. In the present study, we investigated the effects of DIF-1 and its ...

We examined, in soleus muscle, the effects of prolonged palmitate exposure (0, 6, 12, 18 h) on insulin-stimulated glucose transport, intramuscular lipid accumulation and oxidation, activation of selected insulin-signaling proteins, and the insulin-stimulated translocation of GLUT4. Insulin-stimulated glucose transport was progressively reduced after 6 h (-33%), 12 h (-66%), and ...