Increased Insulin Sensitivity and Cellular Insulin Binding in Obese Diabetics Following Treatment With Glibenclamide

Beck‐Nielsen, Henning; Pedersen, Oluf; Lindskov, H O

doi:10.1530/acta.0.0900451

Cited by 137 publications

(46 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is well established that the insulin receptor capacity is inversely related to the insulin plasma levels in the state of insulin deficiency [22,23]. Decreasing insulin levels during sulphonylurea therapy were observed earlier by different investigators [19,20] and also recently by Lunetta et al [21] and by Beck-Nielsen et al [18] with adult-onset diabetic patients. (3) Another explanation for the discrepancy could be that factors as yet unknown might be involved, since in all experiments where an increase in insulin binding could be observed the drug was given orally.…”

Section: Discussionmentioning

confidence: 78%

See 1 more Smart Citation

Extrapancreatic action of the sulphonylurea gliquidone: post-receptor effect on insulin-stimulated glycogen synthesis in rat hepatocytes in primary culture

et al. 1984

View full text Add to dashboard Cite

Summary. The effects of a sulphonylurea, gliquidone, on insulin binding and the insulin induced rate of glycogen synthesis, were studied in rat hepatocytes in primary culture. Hepatocytes were cultured for 48 h. During the second 24 h of this period, the hepatocytes were incubated with or without gliquidone (5 mg/1). The binding of 125I-insulin and the insulin stimulation of glycogen synthesis from aac-glucose were measured. Gliquidone influenced neither insulin binding nor the basal rate of glycogen synthesis, but it did enhance the effect of insulin on glycogen synthesis. Responsiveness was increased by gliquidone at all insulin concentrations used (10-10,000 mU/1); at 1000 mU/1 the drug increased glycogen synthesis from 310 to 430% above the basal rate. Half-maximal stimulation was reached in control cells at an insulin concentration of 95 mU/l and in gliquidone-treated cells at 94 mU/1, which indicates unchanged insulin sensitivity. Based on these experiments with cultured rat hepatocytes it appears that the extrapancreatic action of gliquidone is not mediated by an effect on insulin binding.

show abstract

Section: Discussionmentioning

confidence: 78%

“…Also an increased number of insulin receptors was observed in circulating monocytes of non-insulin-dependent diabetic patients treated with sulphonylureas [1,18]. It is at present not clear why these findings in vivo are not in agreement with the majority of studies in vitro.…”

Section: Discussionmentioning

confidence: 92%

Extrapancreatic action of the sulphonylurea gliquidone: post-receptor effect on insulin-stimulated glycogen synthesis in rat hepatocytes in primary culture

et al. 1984

View full text Add to dashboard Cite

show abstract

“…Glibenclamide is a sulphonylurea which has been widely used in the management of non-insulin dependent diabetes mellitus [4][5][6] . Nevertheless, there are reports that glibenclamide can induce hypoglycemia, even at low doses, especially in the elderly 7,8 .…”

Section: Introductionmentioning

confidence: 99%

Glibenclamide-pregnenolone derivative has greater hypoglycemic effects and biodistribution than glibenclamide-OH in alloxan-rats

Figueroa‐Valverde¹,

Díaz-Cedillo²,

Lopez-Ramos³

et al. 2012

BIOMED PAP

View full text Add to dashboard Cite

Aim. The present study was designed to investigate the activity of two glibenclamide derivatives on glucose concentration. An additional aim was to identify the biodistribution of glibenclamide derivatives in different organs in a diabetic animal model. Methods. The effects of two glibenclamide derivatives on glucose concentration were evaluated in a diabetic animal model. In addition, glibenclamide derivatives were bound to Tc-99m using radioimmunoassay methods. To evaluate the pharmacokinetics of the glibenclamide derivatives over time (15, 30, 45 and 60 min) the Tc-99m-glibenclamide conjugates were used. Results. The results showed that glibenclamide-pregnenolone had greater hypoglycemic activity than glibenclamide or glibenclamide-OH. The data also showed that the biodistribution of Tc-99m-glibenclamide-OH in all organs was less than that of the Tc-99m-glibenclamide-pregnenolone derivative. Conclusions. The glibenclamide-pregnenolone derivative had greater hypoglycemic effects and its biodistribution was wider than glibenclamide-OH. The data suggest that the steroid nucleus may be important to the hypoglycemic activity of the glibenclamide-pregnenolone derivative and this could be related to the degree of lipophilicity induced by the steroid nucleus in the chemical structure of glibenclamide-pregnenolone.

show abstract

“…Although there are discordam results in the literature [15], the weight of experimental evidence indicates that sulfonylureas act in part by increasing sensitivity to insulin in peripheral tissues. Initial studies on the effects of sulfonylureas in peripheral tissues concentrated on possible changes in insulin receptor number [10,11,16,17] but recent attention has focused on post-receptor actions [5,8,12,13].…”

mentioning

confidence: 99%

Augmentation of the effects of insulin and insulin-like growth factors I and II on glucose uptake in cultured rat skeletal muscle cells by sulfonylureas

1987

View full text Add to dashboard Cite

Summary. The effect of sulfonylureas on long-term regulation of glucose uptake by insulin and insulin-like growth factors has been studied in the L6 line of cultured skeletal muscle cells. These cells have previously been shown to possess many characteristics of differentiated skeletal muscle and to bind and respond to physiological concentrations of insulin and insulin-like growth factors I and II. Tolazamide (halfmaximal at 0.2 mg/ml) augments the effects of insulin, insulin-like growth factor I, and insulin-like growth factor II on glucose uptake, increasing both sensitivity and maximal efficacy of the hormones. In the absence of added hormone, tolazamide has no effect on glucose uptake. A similar increase in insulin-stimulated glucose uptake with unaltered basal uptake occurs with glybufide (half-maximal at 0.5 ~g/ml). The action of tolazamide requires long-term exposure to the sulfonylurea (22 h) and is inhibited by cycloheximide, suggesting a process that involves new protein synthesis. In contrast to glucose uptake, amino acid uptake in L6 cells is increased by tolazamide in the absence of hormones. Insulin and the insulin-like growth factors also stimulate amino acid uptake, but this effect is not further augmented by tolazamide. Thus, sulfonylureas appear to directly modulate amino acid uptake, but to indirectly augment glucose uptake through an effect on insulin and insulin-like growth factor stimulated pathways. Neither insulin binding nor insulin degradation is altered by tolazamide, indicating a post-binding mechanism of action. The L6 cultured skeletal muscle cell line should be useful in future studies on the mechanism of the extrapancreatic actions of sulfonylureas.

show abstract

Increased Insulin Sensitivity and Cellular Insulin Binding in Obese Diabetics Following Treatment With Glibenclamide

Abstract: The aim of the present study was to examine the effect of glibenclamide on the insulin receptors, the insulin sensitivity and the insulin secretion in obese non-ketotic diabetics.

Cited by 137 publications

References 7 publications

Extrapancreatic action of the sulphonylurea gliquidone: post-receptor effect on insulin-stimulated glycogen synthesis in rat hepatocytes in primary culture

Extrapancreatic action of the sulphonylurea gliquidone: post-receptor effect on insulin-stimulated glycogen synthesis in rat hepatocytes in primary culture

Glibenclamide-pregnenolone derivative has greater hypoglycemic effects and biodistribution than glibenclamide-OH in alloxan-rats

Augmentation of the effects of insulin and insulin-like growth factors I and II on glucose uptake in cultured rat skeletal muscle cells by sulfonylureas

Contact Info

Product

Resources

About