Synergistic effects of troglitazone and oleate on the translatability of preproinsulin mRNA from INS-1 cells

Bollheimer, Leo Cornelius; Kagerbauer, Simone Maria; Buettner, Roland; Kemptner, Daniela; Palitzsch, K. D.; Schölmerich, Jürgen; Hügl, Sigrun R.

doi:10.1016/s0006-2952(02)01352-7

Cited by 5 publications

(7 citation statements)

References 51 publications

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“…This could be due to the aforementioned sparing effect in insulin secretion, particularly as there was no significant change in pulse label-quantified PPI biosynthesis or mRNA content in comparison with the corresponding controls. This is in accord with our previous study with INS-1 cells, where troglitazone per se did not affect parameters of PPI transcription and translation at high glucose levels (c glucose =11·2 mM) (Bollheimer et al 2002). Principally, we cannot exclude other mechanisms, e.g.…”

Section: Islet Hormone Synthesissupporting

confidence: 89%

“…In rat pancreatic islets, Masuda et al (1995) described a dose-dependent effect of troglitazone with a potentiation of insulin secretion at doses of 1-10 µM and a diminution at doses of 100 µM. In the pharmacologically relevant range of 5-10 µM troglitazone, we and others have observed only marginal changes in insulin release when using the clonal beta-cell lines HIT or INS-1 (Ohtani et al 1998, Bollheimer et al 2002, Kawai et al 2002.…”

Section: Introductionmentioning

confidence: 64%

“…To our knowledge, these aspects of troglitazone action on primary pancreatic islets have not been analyzed in detail before, thereby limiting the possibility of comparing our results with other studies (Bollheimer et al 2002, Schinner et al 2002.…”

Section: Islet Hormone Synthesismentioning

confidence: 89%

“…In the clonal beta-cell line INS-1, a stable to a decreasing insulin release has been reported after prolonged (4 h) as well as chronic (48 h) exposure to 10 µM troglitazone (Bollheimer et al 2002, Kawai et al 2002. The studies cited above illuminate the controversy about troglitazone-induced changes of insulin secretion in vitro.…”

Section: Islet Hormone Secretionmentioning

confidence: 95%

“…Troglitazone was used in a standard concentration of 10 µM with dimethylsulfoxide (DMSO) as vehicle for solubilization (c final [DMSO] =0·01% v/v) (Bollheimer et al 2002, Cnop et al 2002, Kawai et al 2002. The latter was added at the same concentration to the non-troglitazone-containing samples.…”

Section: Concentration Of Troglitazone and Oleatementioning

confidence: 99%

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Insulin-sparing effects of troglitazone in rat pancreatic islets

Bollheimer

Troll²,

Landauer³

et al. 2003

Journal of Molecular Endocrinology

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Thiazolidinediones (TZDs) have been suggested to act beneficially on pancreatic islet function and on beta-cell viability but data concerning direct effects on isolated islets are controversial. Therefore, we have examined parameters of pancreatic insulin and glucagon secretion and biosynthesis in TZD-exposed rat pancreatic islets under physiological glucose level conditions and under conditions of glucolipotoxicity.Primary rat islets were incubated for 2·5 h with or without troglitazone (10 µM) in 5·6 mM glucose (standard glucose levels) and 16·7 mM glucose (high glucose levels); a subgroup was additionally treated with oleate (200 µM) to simulate acute glucolipotoxicity. Insulin and glucagon secretion, intracellular content and their respective mRNAs were quantified. Newly synthesized insulin was determined by pulse-labeling experiments.Troglitazone reduced insulin secretion at standard and high glucose levels by about one-third (P≤0·05). Insulin content was decreased at 5·6 mM glucose but increased at 16·7 mM glucose by the presence of troglitazone (P≤0·05). Newly synthesized insulin mRNA and preproinsulin mRNA decreased by about 20% at standard glucose levels (P≤0·05). Glucagon secretion was augmented by troglitazone in islets under high glucose conditions by an additional 50% (P≤0·05). No clear beneficial troglitazone effects were observed under glucolipotoxic conditions.The reduced insulin secretion and biosynthesis at standard glucose levels can be interpreted as an insulin-sparing effect. Troglitazone effects were less pronounced at high glucose alone or in combination with oleate. From a clinical point of view, these results indicate a greater benefit of troglitazone for beta-cell function in hyperinsulinemic, but normoglycemic patients with insulin resistance or early type 2 diabetes without major insulin secretion deficits and/or pronounced hyperglycemia.

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Section: Islet Hormone Synthesissupporting

confidence: 89%

Section: Introductionmentioning

confidence: 64%

Section: Islet Hormone Synthesismentioning

confidence: 89%

Section: Islet Hormone Secretionmentioning

confidence: 95%

Section: Concentration Of Troglitazone and Oleatementioning

confidence: 99%

See 3 more Smart Citations

Insulin-sparing effects of troglitazone in rat pancreatic islets

Bollheimer

Troll²,

Landauer³

et al. 2003

Journal of Molecular Endocrinology

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β-Cell preservation with thiazolidinediones

Campbell¹,

Mariz²

2007

Diabetes Research and Clinical Practice

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Pioglitazone and Sodium Salicylate Protect Human β-Cells against Apoptosis and Impaired Function Induced by Glucose and Interleukin-1β

Zeender

Maedler²,

Bosco

et al. 2004

The Journal of Clinical Endocrinology &Amp; Metabolism

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Decreased functional beta-cell mass in type 1 and type 2 diabetes is due to beta-cell apoptosis and impaired secretory function suggested to be mediated, in part, by immune- and/or high-glucose-induced production of IL-1beta acting through the nuclear factor kappaB (NFkappaB)/Fas pathway. The aim of this study was to determine whether two drugs believed to block NFkappaB activation, the thiazolidinedione (glitazone) pioglitazone and the nonsteroidal antiinflammatory drug sodium salicylate, can protect human beta-cells against the toxic effects of IL-1beta and high glucose in vitro. Human islets were maintained in culture 2-4 d at 100 mg/dl (5.5 mm) glucose with or without (control) IL-1beta or at 600 mg/dl (33.3 mm) glucose. IL-1beta and 600 mg/dl glucose increased beta-cell apoptosis and abolished short-term glucose-stimulated insulin secretion. Both drugs protected partially against loss of glucose-stimulated insulin secretion and prevented completely increased apoptosis caused by IL-1beta or 600 mg/dl glucose. IL-1beta secretion from islets was increased by 4-d culture at 600 mg/dl, and this was blocked by pioglitazone. Both drugs prevented activation of beta-cell NFkappaB by high glucose. Pioglitazone and sodium salicylate thus protect human islets against the detrimental effects of IL-1beta and high glucose by blocking NFkappaB activation and may therefore be useful in retarding the manifestation and progression of diabetes.

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Synergistic effects of troglitazone and oleate on the translatability of preproinsulin mRNA from INS-1 cells

Cited by 5 publications

References 51 publications

Insulin-sparing effects of troglitazone in rat pancreatic islets

Insulin-sparing effects of troglitazone in rat pancreatic islets

β-Cell preservation with thiazolidinediones

Pioglitazone and Sodium Salicylate Protect Human β-Cells against Apoptosis and Impaired Function Induced by Glucose and Interleukin-1β

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