The insulin signal and its effects on the pyruvate dehydrogenase complex in cirulating lymphocytes of obese children

Curto, M; Piccinini, Marco; Cerutti, Fránco; Rabbone, Ivana; Mostert, M.; Sacchetti, C; Bruno, R.; Rinaudo, M.

doi:10.1016/0020-711x(92)90021-r

Cited by 9 publications

(27 citation statements)

References 39 publications

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“…Circulating lymphocyte preparation was performed according to Boyu Èm as previously reported. 1,3 At the end of preparation, cells were suspended in 110 mm NaCl buffered in 40 mm Na 2 HPO 4 ± KH 2 PO 4 pH 7.4 (PBS-A). One part of the preparation was used immediately for insulin contact procedures, another part for cell counts, performed manually with a haemocytometer, and the remainder was pelleted, suspended in PBS-A enriched with 2 mgaml leupeptin and 20 mM EDTA (PBS-B), stored at 770 C and eventually used to evaluate PDH activity.…”

Section: Lymphocyte Preparationmentioning

confidence: 99%

In obese individuals dexfenfluramine corrects molecular derangements reflecting insulin resistance

et al. 2000

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BACKGROUND: Circulating lymphocytes of obese individuals with and without type 2 diabetes have derangements of pyruvate dehydrogenase (PDH) that are described as re¯ecting a disorder underlying systemic insulin resistance, namely basal activity below normal and, in vitro, unresponsiveness to insulin at 33 pmolal and activation at 330 pmolal instead of activation and inhibition as in controls. OBJECTIVE: To explore whether the above enzyme derangements are overcome in obese individuals on dexfenuramine treatment, known to improve poor peripheral insulin sensitivity.

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Section: Lymphocyte Preparationmentioning

confidence: 99%

In obese individuals dexfenfluramine corrects molecular derangements reflecting insulin resistance

et al. 2000

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“…Since in both cell groups activation takes only 15 min, the difficulties with phosphatase suggested above should not imply a quantitative enzyme defect. PDHP phosphatase is considered to be the insulin target [15][16][17][27][28][29][30] and patients insulin alone [8,22,24,25,32], or in reported evidence [16,17,28,[35][36][37][38][39][40][41].…”

Section: Drug Effect (E) In Terms Ofmentioning

confidence: 99%

“…Blood samples for assays of blood sugar and insulin and for both in 0. [32]; the latter was tested according Results to Allred & Guy as previously described [32].…”

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confidence: 99%

“…Lymphocyte preparation was performed according to Boyüm as already described [32]. At the end of preparation, cells forms, active dephosphorylated (PDHa) and inactive phosphorylated (PDHb).…”

mentioning

confidence: 99%

“…At the end of preparation, cells forms, active dephosphorylated (PDHa) and inactive phosphorylated (PDHb). The balance between the two forms is were suspended in 110 mm NaCl buffered in 40 mm phosphate buffer pH 7.4 (PBS A) and identified by controlled by PDH kinase and PDHP phosphatase.The latter is activated by mm Ca ++ and mm Mg ++ and inhibited morphological, biochemical and immunological techniques [32]; in all preparations, the cell suspension consisted of by mm fluoride [26] and there is evidence that it constitutes the actual insulin target [15][16][17][27][28][29][30].…”

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Molecular effects of sulphonylurea agents in circulating lymphocytes of patients with non‐insulin‐dependent diabetes mellitus

Rabbone¹,

Piccinini²,

Curto³

et al. 1998

Brit J Clinical Pharma

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Aims In circulating lymphocytes of NIDDM patients pyruvate dehydrogenase (PDH), the major determinant in glucose consumption through oxidative pathways, is poorly active. The aim of this study is to examine whether sulphonylurea drug treatment revives PDH activity in circulating lymphocytes from NIDDM patients. Methods Twenty normal-weight individuals with NIDDM were enrolled in this study. They had maintained their glycaemic levels close to normal by means of a restricted diet that had no longer been successful in the proceeding 2 months. The treatment protocol consisted in 160 mg gliclazide daily for 5 weeks. Twenty healthy subjects, matched for age, body mass index and gender, were enrolled as a control group. Patients, before and after treatment, as well as controls were tested for PDH activity in their circulating lymphocytes. Nine other untreated patients and nine healthy subjects, with the above mentioned characteristics, were recruited for the assay of PDH activity in their circulating lymphocytes before and after exposure, in vitro, to gliclazide, to insulin, and to gliclazide and insulin in combination. Results In gliclazide-treated NIDDM patients, PDH activity in circulating lymphocytes recovered. In vitro, in circulating lymphocytes of untreated patients and controls insulin at 5 mU ml −1 was ineffective and highly effective, respectively, in raising enzyme activity; gliclazide at 10 ng ml −1 was ineffective on PDH in both groups, but in combination with insulin at 5 mU ml −1 in both groups PDH was as active as in cells of controls exposed to insulin only. In cells of controls, gliclazide alone at 25-50 ng ml −1 caused enzyme activation, whereas above 50 ng ml −1 it caused inhibition; in cells of patients below 50 ng ml −1 it had no effects, but at 50 ng mland above raised enzyme activity to the basal level of controls. Conclusions This study suggests that free gliclazide concentrations determine recovery of PDH activity in circulating lymphocytes of treated patients through drug-mediated enhanced insulin control over PDH or through the drug alone.Keywords: NIDDM, sulphonylureas, pyruvate dehydrogenase, circulating lymphocytescells. An understanding of the mechanisms underlying this Introduction benefit might throw new light on the mechanisms through which sulphonylureas behave as hypoglycaemic agents. Sulphonylurea drugs are largely employed to lower hyperglycaemia in patients with NIDDM. The mechanism In NIDDM patients systemic glucose consumption through oxidative pathways is abnormal and in tissues underlying this effect is still debated. Evidence indicates these drugs improve cell responsiveness to insulin or even actively involved in preserving glucose homeostasis, such as skeletal muscle [9][10][11], this alteration is accompanied by mimic some of the effects of insulin [1][2][3][4][5][6][7]. In a previous study it was observed that in circulating lymphocytes of poorly active PDH [12,13]. Further, in adipocytes from these patients [14] enzyme response to insulin is impaired. NIDDM patients the...

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Enhanced Activity of the Plasma Membrane Oxidoreductase in Circulating Lymphocytes from Insulin-Dependent Diabetes Mellitus Patients

Lenaz

Paolucci

Fato

et al. 2002

Biochemical and Biophysical Research Communications

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The insulin signal and its effects on the pyruvate dehydrogenase complex in cirulating lymphocytes of obese children

Cited by 9 publications

References 39 publications

In obese individuals dexfenfluramine corrects molecular derangements reflecting insulin resistance

In obese individuals dexfenfluramine corrects molecular derangements reflecting insulin resistance

Molecular effects of sulphonylurea agents in circulating lymphocytes of patients with non‐insulin‐dependent diabetes mellitus

Enhanced Activity of the Plasma Membrane Oxidoreductase in Circulating Lymphocytes from Insulin-Dependent Diabetes Mellitus Patients

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