Effects of tolbutamide on insulin binding to isolated fat cells of the rat

Joost, Hans‐Georg; Arend, Wolfgang; Holze, Susanne

doi:10.1016/0006-2952(82)90008-9

Cited by 25 publications

(5 citation statements)

References 25 publications

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“…Insulin binding of isolated adipocytes was not modulated by tolbutamide. 34 The present results demonstrating the absence of direct effects of glyburide on insulin binding and insulin-induced downregulation of insulin receptors is in contrast to the findings of Prince and Olefsky, 18 who showed a 19% increase in insulin binding and a 34% inhibition of insulin-induced receptor loss in cultured human fibroblasts. However, Vigneri et al 19 were unable to reproduce these results, and Salhanick et al 33 estimated the small (12%) increase in high-affinity binding observed only in hepatocytes cultured in the absence of insulin as of questionable physiologic significance.…”

Section: Discussioncontrasting

confidence: 99%

Modulation by a Sulfonylurea of Insulin-dependent Glycogenesis, but Not of Insulin Binding, in Cultured Rat Hepatocytes: Evidence for a Postreceptor Mechanism of Action

et al. 1984

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To detect potential direct effects of the sulfonylurea glyburide on hepatic carbohydrate metabolism, we tested whether the drug was capable of modulating insulin binding and glycogenesis in primary cultured hepatocytes. After 24-h culture under serum- and hormone-free conditions, cells were incubated with or without 10(-8) M insulin and/or glyburide (0.1-5.0 micrograms/ml) for another 24 h. Then, specific 125I-insulin binding and basal and insulin-stimulated glycogen synthesis were determined. Acute addition of glyburide to previously untreated cells did not modulate any of these parameters. Incubation for 24 h with 2 micrograms/ml of glyburide did not affect the DNA and protein content of the dishes. Cellular glycogen content and basal glycogenesis also remained unchanged by glyburide in hepatocytes incubated in the absence of insulin, but glycogen content was increased and basal glycogen synthesis decreased in insulin-pretreated cells. In contrast, glyburide increased insulin-stimulated glycogenesis in a dose-dependent fashion in both insulin-pretreated and control cells by enhancing responsiveness, but not sensitivity, toward insulin. Pretreating hepatocytes with 10(-8) M insulin caused a 40% reduction in specific insulin binding. Glyburide did not modulate insulin binding or degradation in control cells nor was insulin-induced regulation of insulin receptors affected. These results demonstrate a direct dose-dependent effect of a sulfonylurea on an insulin action toward hepatic carbohydrate metabolism, and suggest that this effect is mediated by a postreceptor mechanism.

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Section: Discussioncontrasting

confidence: 99%

Modulation by a Sulfonylurea of Insulin-dependent Glycogenesis, but Not of Insulin Binding, in Cultured Rat Hepatocytes: Evidence for a Postreceptor Mechanism of Action

et al. 1984

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“…In hepatocytes in culture, Fleig et al [5] could not observe a change in insulin binding in glibenclamide-treated cells. In other culture systems with adipocytes [6,16], human skin fibroblasts, IM-9 lymphoblasts, MCF-7 human mammary carcinoma or H 35 rat hepatoma cells [17] different sulphonylurea drugs also showed no effect on insulin binding. Only Prince and Olefsky [4] observed a modest increase in insulin receptors in human fibroblasts in culture.…”

Section: Discussionmentioning

confidence: 90%

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

et al. 1984

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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.

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“…It is unlikely that tolbutamide itself contributed to the observed prolongation of insulin action. Although in vitro studies have suggested a direct tolbutamide action on glucose metabolism (27)(28)(29), a recent in vivo human study did not show such an effect (30). Nevertheless, tolbutamide-induced proinsulin release could play a role (Fig.…”

Section: Discussionmentioning

confidence: 98%

Differences Between the Tolbutamide-Boosted and the Insulin-Modified Minimal Model Protocols

et al. 1997

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The insulin-modified frequently sampled intravenous glucose tolerance test (FSIGTT) with minimal model analysis (MINMOD) was compared with the tolbutamide protocol and the glucose clamp in 35 nondiabetic subjects (age 38 +/- 2 years [mean +/- SE], BMI 27.2 +/- 0.9 kg/m2). Each subject underwent two FSIGTTs, one with tolbutamide (300 mg) and the other with insulin (0.03 U/kg) and a euglycemic hyperinsulinemic clamp (40 mU x m(-2) x min(-1)). Insulin sensitivity was determined from each FSIGTT with MINMOD and from the clamp. Insulin sensitivity indexes (S(I)) from the two FSIGTTs were significantly correlated (r = 0.77, P < 0.001), but S(I(insulin)) was 29 +/- 4% lower than S(I(tolbutamide)). Both S(I(insulin)) and S(I(tolbutamide)) correlated significantly with S(I(clamp)) (r = 0.70 and 0.71, P < 0.001 for each). Expressed in the same units (dl/min per pU/ml), S(I(tolbutamide)) was on average 13 +/- 6% lower than S(I(clamp)) (4.51 +/- 0.40 vs. 5.36 +/- 0.36 x 10(-2), P = 0.009), whereas S(I(insulin)) was 44 +/- 4% lower. S(G(tolbutamide)) and S(G(insulin)) were not different (1.88 +/- 0.10 vs. 2.01 +/- 0.09 x 10(-2) min(-1), P = 0.167) and were significantly correlated (r = 0.50, P = 0.002). Thus, insulin sensitivity estimates from both protocols correlate significantly with each other and with the clamp. They are quantitatively discrepant, however, possibly due to differences in the route of insulin delivery, saturation of insulin action, and/or tolbutamide-induced proinsulin release. Data obtained from these two MINMOD protocols are not directly comparable, and the same protocol must be used in any single cross-sectional or longitudinal study.

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Effects of tolbutamide on insulin binding to isolated fat cells of the rat

Cited by 25 publications

References 25 publications

Modulation by a Sulfonylurea of Insulin-dependent Glycogenesis, but Not of Insulin Binding, in Cultured Rat Hepatocytes: Evidence for a Postreceptor Mechanism of Action

Modulation by a Sulfonylurea of Insulin-dependent Glycogenesis, but Not of Insulin Binding, in Cultured Rat Hepatocytes: Evidence for a Postreceptor Mechanism of Action

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

Differences Between the Tolbutamide-Boosted and the Insulin-Modified Minimal Model Protocols

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