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

Begum, Najma; Draznin, Boris

doi:10.1172/jci115988

Cited by 37 publications

(14 citation statements)

References 39 publications

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“…Although marked hyperglycaemia was observed in the diabetic rats, whether NO has a physiological role in the control of AVP and oxytocin responses to hyperglycaemia remains unknown. As phlorizin, a continuous inhibitor of renal tubular reabsorption of glucose, is a useful drug with which to distinguish between the roles of hyperglycaemia and hypoinsulinaemia in the regulation of nNOS gene expression in the PVN and SON, we made phlorizin-treated rats according to the previously published protocol [25]. The phlorizin-treated rats with diet showed the reduction of nNOS gene in the PVN and SON by normalizing the hyperglyca- Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, to normalize the glucose levels in STZ-induced diabetic rats, phlorizin (Sigma, St. Louis, Mo., USA) (0.4 g × kg body weight 1 × day 1 ); made up as a 25 % solution in propylene glycol, was administered s. c. every 8 h for 12 days in STZ-induced diabetic rats, according to the published protocol [25]. In Group I phlorizin (0.4 kg × kg body weight 1 × day 1 ) was s. c. administered every 8 h for 12 days in normal rats (n = 6).…”

Section: Methodsmentioning

confidence: 99%

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Upregulation of hypothalamic nitric oxide synthase gene expression in streptozotocin-induced diabetic rats

et al. 1998

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The peripheral administration of streptozotocin (STZ) causes marked hyperglycaemia, plasma hyperosmolality, hypoinsulinaemia, hyperphagia and polydipsia. In STZ-induced diabetic animals, insulin treatment reverses these symptoms. Several studies have demonstrated that insulin deficiency induced diabetes causes alteration of hypothalamic transmitters and the gene expressions of neuropeptides [1±7]. These studies suggest that the alteration of monoamine and neuropeptides in the hypothalamus may play a role in the multiple behavioural and hormonal abnormalities in STZ-induced diabetic rats.Recent studies have demonstrated that nitric oxide (NO) may be associated with various functions of the central nervous system, including feeding [8±12] and drinking behaviour [13,14]. It has been demonstrated that both systemic administration of a competitive antagonist of NO synthase (NOS) and Diabetologia (1998) Summary Plasma arginine vasopressin (AVP) is known to be elevated in patients with uncontrolled insulin-dependent diabetes mellitus who have plasma hyperosmolality with hyperglycaemia. Although osmotic stimuli cause an increase in nitric oxide synthase (NOS) activity as well as synthesis of AVP and oxytocin in the paraventricular (PVN) and supraoptic nuclei (SON), it is not known whether NOS activity in the hypothalamus changes in the diabetic patients who have plasma hyperosmolality with hyperglycaemia caused by insulin deficiency. Expression of the neuronal (n) NOS gene in the PVN and SON in streptozotocin (STZ)-induced diabetic rats was investigated by using in situ hybridization histochemistry and NADPH-diaphorase histochemical staining. Four weeks after intraperitoneal (i. p.) administration of STZ, male Wistar rats developed hyperglycaemia and plasma hyperosmolality. The expression of nNOS gene and NADPH-diaphorase staining in the PVN and SON remarkably increased in STZ-induced diabetic rats compared to control rats. Three weeks after administration of STZ, the diabetic rats were subcutaneously treated with insulin for 1 week, which resulted in significant suppression of the induction of nNOS, AVP and oxytocin gene expression in the PVN and SON. Furthermore, the induction of nNOS gene expression in the PVN and SON was suppressed in STZ-induced diabetic rats treated with phlorizin and diet to normalize hyperglycaemia without insulin treatment. These results suggest that upregulation of nNOS gene expression as well as AVP and oxytocin gene expression in the PVN and SON in STZ-induced diabetic rats may be associated with hyperglycaemia and plamsa hyperosmolality. [Diabetologia (1998) 41: 640±648]

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Upregulation of hypothalamic nitric oxide synthase gene expression in streptozotocin-induced diabetic rats

et al. 1998

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“…Since glimepiride and insulin stimulations are additive only, glimepiride may regulate GLUT4 translocation by bypassing the insulin signal transduction cascade. Elevated levels of phosphorylated GLUT4 in isolated rat adipocytes incubated with glucose, insulin and glutamine in primary culture [12], or in rat adipocytes isolated from Streptozotocin-diabetic rats [55], have been correlated with diminished glucose transport activity [56]. There is some evidence for Ser/Thr-phosphorylation of GLUT4 by PKA during induction of insulin resistance [57][58][59].…”

Section: Discussionmentioning

confidence: 99%

Stimulation of glucose utilization in 3T3 adipocytes and rat diaphragm in vitro by the sulphonylureas, glimepiride and glibenclamide, is correlated with modulations of the cAMP regulatory cascade

Müller

Wied

Wetekam

et al. 1994

Biochemical Pharmacology

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Abstract--The long-term hypoglycemic activity of sulphonylurea drugs has been attributed, in part at least, to the stimulation of glucose utilization in extra-pancreatic tissues. The novel sulphonylurea, glimepiride, gives rise to a longer lasting reduction in the blood sugar level in dogs and rabbits compared to glibenclamide (Geisen K, Drug Res 38: 1120-1130). This cannot be explained adequately by elevated plasma insulin levels. This study investigated whether this prolonged hypoglycemic phase was based on the drug's abilities to stimulate glucose utilization and affect the underlying regulatory mechanisms in insulin-sensitive cells in vitro. It was found that in the absence of added insulin, glimepiride and glibenclamide (1-50/iM) stimulated lipogenesis (3T3 adipocytes) and glycogenesis (isolated rat diaphragm) -4.5-and 2.5-fold, respectively, and reduced the isoproterenol-stimulated lipolysis (rat adipocytes) up to 40-60%. The increased glucose utilization was correlated with a 3-4-fold higher 2-deoxyglucose transport rate and amount of GLUT4 at the plasma membrane, as well as with increased activities of key metabolic enzymes (glycerol-3-phosphate acyltransferase, glycogen synthase) within the same concentration range. Furthermore, the low K,, cAMP-specific phosphodiesterase was activated 1.8-fold, whereas the cytosolic cAMP level and protein kinase A activity ratios were significantly lowered after incubation of isoproterenol-stimulated rat adipocytes with the sulphonylureas. In many of the aspects studied the novel sulphonylurea, glimepiride, exhibited slightly lower EDs0-values than glibenclamide. This study demonstrates correlations existing between druginduced stimulation of glucose transport/metabolism and cAMP degradation/protein kinase A inhibition as well as between the relative efficiencies of,glimepiride and glibenclamide in inducing these extrapancreatic processes. Therefore, it is suggested that the stimulation of glucose utilization by sulphonylureas is mediated by a decrease of cAMP-dependent phosphorylation of GLUT4 and glucose metabolizing enzymes. The therapeutic relevance of extra-pancreatic effects of sulphonylureas, in general, and of the differences between glimepiride and glibenclamide as observed in vitro in this work, in particular, remain to be elucidated.

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“…The procedure is described in a previous publication (22). In brief, cells in 12-well dishes were serum deprived for 16 h and incubated with TNF-α (20 ng/ml) for 6 h followed by insulin 100 nmol/l for 5 min at 37 ºC.…”

Section: Measurement Of 2-deoxyglucose (2-dog) Uptakementioning

confidence: 99%

The Effect of Tumor Necrosis Factor-.ALPHA. on Tissue Specificity and Selectivity to Insulin Signaling

et al. 2003

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

Cited by 37 publications

References 39 publications

Upregulation of hypothalamic nitric oxide synthase gene expression in streptozotocin-induced diabetic rats

Upregulation of hypothalamic nitric oxide synthase gene expression in streptozotocin-induced diabetic rats

Stimulation of glucose utilization in 3T3 adipocytes and rat diaphragm in vitro by the sulphonylureas, glimepiride and glibenclamide, is correlated with modulations of the cAMP regulatory cascade

The Effect of Tumor Necrosis Factor-.ALPHA. on Tissue Specificity and Selectivity to Insulin Signaling

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