Regulation of GLUT-4 Phosphorylation by Intracellular Calcium in Adipocytes*

Reusch, Jane E.B.; Begum, Najma; Sussman, Karl E.; Draznin, Boris

doi:10.1210/endo-129-6-3269

Cited by 119 publications

(74 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Regulation of GLUT4 phosphorylation by insulin and glimepiride. Reports from several laboratories indicate that phosphorylation of GLUT4 at serine/threonine resi dues by isoproterenol-stimulated PKA (46) or Ca 2+ / calmodulin-dependent protein kinase (53) or inhibition of protein phosphatases 1 and 2 A by okadaic acid (47,47a) reduces the insulin-stimulated glucose trans port in isolated rat adipocytes. Therefore, one possible mechanism for desensitization of the glucose transport and GLUT translocation for insulin stimulation may reside in an increased phosphorylation state of GLUT4.…”

Section: Discussionmentioning

confidence: 99%

The sulfonylurea drug, glimepiride, stimulates glucose transport, glucose transporter translocation, and dephosphorylation in insulin-resistant rat adipocytes in vitro

Müller¹,

Wied²

1993

Diabetes

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

The sulfonylurea drug, glimepiride, stimulates glucose transport, glucose transporter translocation, and dephosphorylation in insulin-resistant rat adipocytes in vitro

Müller¹,

Wied²

1993

Diabetes

View full text Add to dashboard Cite

“…Although insulin does not appear to phosphorylate GLUT-4 to promote glucose transport (1 1, 12), other agents that increase its phosphorylation (i.e., isoproterenol, okadaic acid, high levels of cytosolic Ca2+) decrease insulin-stimulated glucose uptake ( 13,14). We hypothesized that excessive phosphorylation ofGLUT-4 may interfere with its responsiveness to stimulation by insulin.…”

Section: Introductionmentioning

confidence: 99%

“…PF and CF were prepared from control and diabetic adipocytes according to the method of King and Sale (21 ). PF and CF (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24) Mg protein/assay) were preincubated for 2 min at 300C.…”

Section: Introductionmentioning

confidence: 99%

Effect of streptozotocin-induced diabetes on GLUT-4 phosphorylation in rat adipocytes.

Begum¹,

Draznin²

1992

J. Clin. Invest.

View full text Add to dashboard Cite

We have examined the regulation of GLUT4 phosphorylation in adipocytes isolated from diabetic rats. Despite progressive (40-70%) reductions in GLUT4 protein contents on the 2nd, 7th, and 14th day of diabetes, the phosphorylation of GLUT4 was increased two-to fourfold. These alterations were accompanied by concomitant reductions (40-66%) in the insulin-stimulated 2-deoxyglucose transport. Insulin treatment of diabetic animals for 5 d restored glucose transport activity, GLUT4 protein, and GLUT4 phosphorylation to control levels whereas vanadate and phlorizin were ineffective. In control adipocytes, insulin promoted GLUT4 translocation from the low density microsomal (LDM) pool to the plasma membranes (PM) and decreased the state of GLUT4 phosphorylation. In adipocytes isolated from the diabetic rats, insulin failed to stimulate GLUT4 translocation and to decrease GLUT4 phosphorylation. To explore the mechanism of the diabetes-induced increases in the GLUT4 phosphorylation, we investigated phosphoserine phosphatase (PSPase) activities using 32P-labeled GLUT4 and phosphorylase "a" as substrates. Diabetes resulted in 50-60% increase in the particulate PSPase activity and concomitant reductions in cytosolic PSPase activities. Although reduced cytosolic PSPase activity correlated with an inadequate dephosphorylation of LDM GLUT4, the existence of highly phosphorylated PM GLUT4 in the presence of increased particulate PSPase activity required additional explanation. To address this problem, we used PM GLUT4 from diabetic rats as a substrate of particulate PSPase. Highly active diabetic particulate PSPase, which dephosphorylated control GLUT4 and phosphorylase a, failed to dephosphorylate PM GLUT4 from diabetic rats. These data suggest that PM GLUT4 from diabetic rats is unable to interact with PSPase or that its phosphorylation sites are not accessible to PSPase action. In summary, an induction of diabetes with streptozotocin resulted in significant increases in GLUT4 phosphorylation.In contrast to normal cells, insulin failed to promote GLUT4 recruitment to the plasma membranes and its dephosphorylation in diabetic adipocytes. At the same time, diabetes appears to induce redistribution of PSPases, resulting in lower cytosolic activity and higher particulate activity. It also appears that the existence of highly phosphorylated GLUT4 in the plasma membranes of diabetic adipocytes resulted from its inability to

show abstract

“…Low-calcium diet increases serum calcitriol, increasing intracellular calcium and, in part, this could result in IR in adipocytes and other insulin target cells mainly by phosphorylation of the glucose transporter type 4 (GLUT4), making insulin-mediated glucose uptake less efficient and promoting systemic IR (Reusch et al 1991, Begum et al 1993, Zemel et al 1995, McCarty et al 2002. In fact, N offspring presented lower serum 25-hydroxyvitamin D 3 and IR.…”

Section: Discussionmentioning

confidence: 99%

Calcium supplementation reverts central adiposity, leptin, and insulin resistance in adult offspring programed by neonatal nicotine exposure

Nobre¹,

Lisboa²,

Santos-Silva³

et al. 2011

Journal of Endocrinology

View full text Add to dashboard Cite

Obesity is a worldwide epidemic. Calcium influences energy metabolism regulation, causing body weight loss. Because maternal nicotine exposure during lactation programs for obesity, hyperleptinemia, insulin resistance (IR), and hypothyroidism, we decided to evaluate the possible effect of dietary calcium supplementation on these endocrine dysfunctions in this experimental model. Osmotic minipumps containing nicotine solution (N: 6 mg/kg per day for 14 days) or saline (C) were s.c. implanted in lactating rats 2 days after giving birth (P2). At P120, N and C offspring were subdivided into four groups: 1) C -standard diet; 2) C with calcium supplementation (CCa, 10 g calcium carbonate/kg rat chow); 3) N -standard diet; and 4) N with calcium supplementation (NCa). Rats were killed at P180. As expected, N offspring showed higher visceral and total body fat, hyperleptinemia, lower hypothalamus leptin receptor (OB-R) content, hyperinsulinemia, and higher IR index. Also, higher tyrosine hydroxylase (TH) expression (C51%), catecholamine content (C37%), and serum 25-hydroxyvitamin D 3 (C76%) were observed in N offspring. Dietary calcium supplementation reversed adiposity, hyperleptinemia, OB-R underexpression, IR, TH overexpression, and vitamin D. However, this supplementation did not reverse hypothyroidism. In NCa offspring, Sirt1 mRNA was lower in visceral fat (K37%) and higher in liver (C42%). In conclusion, dietary calcium supplementation seems to revert most of the metabolic syndrome parameters observed in adult offspring programed by maternal nicotine exposure during lactation. It is conceivable that the reduction in fat mass per se, induced by calcium therapy, is the main mechanism that leads to the increment of insulin action.

show abstract

Regulation of GLUT-4 Phosphorylation by Intracellular Calcium in Adipocytes*

Cited by 119 publications

References 16 publications

The sulfonylurea drug, glimepiride, stimulates glucose transport, glucose transporter translocation, and dephosphorylation in insulin-resistant rat adipocytes in vitro

The sulfonylurea drug, glimepiride, stimulates glucose transport, glucose transporter translocation, and dephosphorylation in insulin-resistant rat adipocytes in vitro

Effect of streptozotocin-induced diabetes on GLUT-4 phosphorylation in rat adipocytes.

Calcium supplementation reverts central adiposity, leptin, and insulin resistance in adult offspring programed by neonatal nicotine exposure

Contact Info

Product

Resources

About