Activation energy of the slowest step in the glucose carrier cycle: break at 23.degree.C and correlation with membrane lipid fluidity

Whitesell, Richard R.; Regen, David M.; Beth, Albert H.; Pelletier, Diana; Abumrad, Nada A.

doi:10.1021/bi00439a042

Cited by 44 publications

(18 citation statements)

References 24 publications

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“…Second, in direct support of our postulate, moderate increases in plasma membrane fluidity have been documented to increase glucose transport [21][22][23]. Studies show that basal glucose transport is not fully active in fat cells and that it can be increased further by augmenting membrane fluidity [21].…”

Section: Introductionsupporting

confidence: 54%

Chromium picolinate positively influences the glucose transporter system via affecting cholesterol homeostasis in adipocytes cultured under hyperglycemic diabetic conditions

Pattar

Tackett

Liu

et al. 2006

Mutation Research/Genetic Toxicology and Environmental Mutagene

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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. Concomitantly, accumulation of intracellularly sequestered glucose transporter GLUT4 at the plasma membrane was dependent on the CrPic-induced cholesterol loss. Since CrPic supplementation has the greatest benefit on glucose metabolism in hyperglycemic insulin-resistant individuals, we asked here if the CrPic effect on cells was glucose-dependent. We found that GLUT4 redistribution in cells treated with CrPic occurs only in cells cultured under high glucose (25 mM) conditions that resemble the diabetic-state, and not in cells cultured under non-diabetic (5.5 mM glucose) conditions. Examination of the effect of CrPic on proteins involved in cholesterol homeostasis revealed that the activity of sterol regulatory element-binding protein (SREBP), a membrane-bound transcription factor ultimately responsible for controlling cellular cholesterol balance, was upregulated by CrPic. In addition, ABCA1, a major player in mediating cholesterol efflux was decreased, consistent with SREBP transcriptional repression of the ABCA1 gene. Although the exact mechanism of Cr 3+ -induced cholesterol loss remains to be determined, these cellular responses highlight a novel and significant effect of chromium on cholesterol homeostasis. Furthermore, these findings provide an important clue to our understanding of how chromium supplementation might benefit hypercholesterolemia-associated disorders.

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Section: Introductionsupporting

confidence: 54%

Chromium picolinate positively influences the glucose transporter system via affecting cholesterol homeostasis in adipocytes cultured under hyperglycemic diabetic conditions

Pattar

Tackett

Liu

et al. 2006

Mutation Research/Genetic Toxicology and Environmental Mutagene

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“…Although intermittent study has coupled membrane fluidity to insulin sensitivity (48)(49)(50), a mechanistic understanding has remained elusive. It is an interesting thought that PM cholesterol trimming may be a common and key antidiabetogenic action of CrPic and metformin, as well as several other antidiabetic agents known to display AMPK-stimulating and cholesterol-lowering properties, e.g.…”

Section: Discussionmentioning

confidence: 99%

Antidiabetogenic Effects of Chromium Mitigate Hyperinsulinemia-Induced Cellular Insulin Resistance via Correction of Plasma Membrane Cholesterol Imbalance

Horvath¹,

Tackett²,

McCarthy³

et al. 2008

Molecular Endocrinology

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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. Here, to gain mechanistic understanding of these separate observations, we tested the prediction that CrPic would protect against insulin-induced insulin resistance by improving PM features important in cytoskeletal structure and insulin sensitivity. We found that insulin-induced insulin-resistant adipocytes display elevated PM cholesterol with a reciprocal decrease in PM PIP2. This lipid imbalance and insulin resistance was corrected by the cholesterol-lowering action of CrPic. The PM lipid imbalance did not impair insulin signaling, nor did CrPic amplify insulin signal transduction. In contrast, PM analyses corroborated cholesterol and PIP2 interactions influencing cytoskeletal structure. Because extensive in vitro study documents an essential role for cytoskeletal capacity in insulin-regulated glucose transport, we next evaluated intact skeletal muscle from obese, insulin-resistant Zucker (fa/fa) rats. Because insulin resistance in these animals likely involves multiple mechanisms, findings that cholesterol-lowering restored F-actin cytoskeletal structure and insulin sensitivity to that witnessed in lean control muscle were striking. Also, experiments using methyl-beta-cyclodextrin to shuttle cholesterol into or out of membranes respectively recapitulated the insulin-induced insulin-resistance and protective effects of CrPic on membrane/cytoskeletal interactions and insulin sensitivity. These data predict a PM cholesterol basis for hyperinsulinemia-associated insulin resistance and importantly highlight the reversible nature of this abnormality.

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“…Because cholesterol causes a highly ordered, gel-like state (9), it is not surprising that a cell's responsiveness to insulin may depend on the cell surface membrane fluidity. In agreement with this postulate, studies have documented that moderate increases in plasma membrane fluidity increase glucose transport (13,36,54). Furthermore, it has been shown that basal glucose transport is not fully active in fat cells and can be increased further by augmenting fluidity (13).…”

Section: Discussionmentioning

confidence: 57%

Sphingomyelinase activates GLUT4 translocation via a cholesterol-dependent mechanism

Liu

Leffler

Weeks

et al. 2004

American Journal of Physiology-Cell Physiology

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dorf. Sphingomyelinase activates GLUT4 translocation via a cholesterol-dependent mechanism. Am J Physiol Cell Physiol 286: C317-C329, 2004. First published October 1, 2003 10.1152/ajpcell. 00073.2003.-A basis for the insulin mimetic effect of sphingomyelinase on glucose transporter isoform GLUT4 translocation remains unclear. Because sphingomyelin serves as a major determinant of plasma membrane cholesterol and a relationship between plasma membrane cholesterol and GLUT4 levels has recently become apparent, we assessed whether GLUT4 translocation induced by sphingomyelinase resulted from changes in membrane cholesterol content. Exposure of 3T3-L1 adipocytes to sphingomyelinase resulted in a time-dependent loss of sphingomyelin from the plasma membrane and a concomitant time-dependent accumulation of plasma membrane GLUT4. Degradation products of sphingomyelin did not mimic this stimulatory action. Plasma membrane cholesterol amount was diminished in cells exposed to sphingomyelinase. Restoration of membrane cholesterol blocked the stimulatory effect of sphingomyelinase. Increasing concentrations of methyl-␤-cyclodextrin, which resulted in a dose-dependent reversible decrease in membrane cholesterol, led to a dose-dependent reversible increase in GLUT4 incorporation into the plasma membrane. Although increased plasma membrane GLUT4 content by cholesterol extraction with concentrations of methyl-␤-cyclodextrin above 5 mM most likely reflected decreased GLUT4 endocytosis, translocation stimulated by sphingomyelinase or concentrations of methyl-␤-cyclodextrin below 2.5 mM occurred without any visible changes in the endocytic retrieval of GLUT4. Furthermore, moderate loss of cholesterol induced by sphingomyelinase or low concentrations of methyl-␤-cyclodextrin did not alter membrane integrity or increase the abundance of other plasma membrane proteins such as the GLUT1 glucose transporter or the transferrin receptor. Regulation of GLUT4 translocation by moderate cholesterol loss did not involve known insulin-signaling proteins. These data reveal that sphingomyelinase enhances GLUT4 exocytosis via a novel cholesterol-dependent mechanism. vesicular trafficking; signal transduction; sphingolipids REMOVAL OF EXCESS GLUCOSE from the circulation involves the stimulation of glucose transport into fat and muscle. In these tissues, the increase in glucose uptake is dependent upon the redistribution of intracellular vesicles containing the insulinresponsive glucose transporter GLUT4 to the plasma membrane. The increase in plasma membrane GLUT4 occurs due to a large increase in the rate of GLUT4 exocytosis, coupled with a smaller decrease in the rate of GLUT4 endocytosis. This translocation localizes GLUT4 at the cell surface, where the transporters subsequently facilitate the influx of glucose into the cell. Activation of this process by insulin involves a complex interplay of intracellular signaling pathways, including a phosphatidylinositol 3-kinase (PI3K) signaling route as well as a proposed PI3K-independent pathway leadi...

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Activation energy of the slowest step in the glucose carrier cycle: break at 23.degree.C and correlation with membrane lipid fluidity

Cited by 44 publications

References 24 publications

Chromium picolinate positively influences the glucose transporter system via affecting cholesterol homeostasis in adipocytes cultured under hyperglycemic diabetic conditions

Chromium picolinate positively influences the glucose transporter system via affecting cholesterol homeostasis in adipocytes cultured under hyperglycemic diabetic conditions

Antidiabetogenic Effects of Chromium Mitigate Hyperinsulinemia-Induced Cellular Insulin Resistance via Correction of Plasma Membrane Cholesterol Imbalance

Sphingomyelinase activates GLUT4 translocation via a cholesterol-dependent mechanism

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