<b>The effects of insulin on transport and metabolism of glucose in skeletal muscle from hyperthyroid and hypothyroid rats</b>

Dimitriadis, George; Parry-Billings, Mark; Bevan, S.; Leighton, Brendan; Krause, U.; Piva, Terrence J.; Tegos, K.; Challiss, R. A. John; Wegener, G.; Newsholme, Eric A.

doi:10.1046/j.1365-2362.1997.1380688.x

Cited by 92 publications

(78 citation statements)

References 35 publications

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“…In agreement with previous results, glucose tolerance was impaired in the hyperthyroid subjects (2, 16); this is due to the insulin resistance primarily at the liver since glucose uptake in peripheral tissues is generally found to be either normal or increased (2,16,17).…”

Section: Discussionsupporting

confidence: 92%

“…In hyperthyroidism, absolute rates of glucose transport in peripheral tissues (such as muscle or adipose tissue) are found to be increased, in order to adapt to high energy demand (2,16,17). Our results suggest that hyperthyroidism increases the sensitivity of the recruitment of GLUT3 and GLUT4 transporters to the cell surface in response to IGF-I, thus contributing to increased glucose transport rates.…”

Section: Discussionmentioning

confidence: 65%

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IGF-I increases the recruitment of GLUT4 and GLUT3 glucose transporters on cell surface in hyperthyroidism

Dimitriadis

Maratou²,

Boutati³

et al. 2008

European Journal of Endocrinology

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Objective: In hyperthyroidism, tissue glucose disposal is increased to adapt to high energy demand. Our aim was to examine the regulation of glucose transporter (GLUT) isoforms by IGF-I in monocytes from patients with hyperthyroidism. Design and methods: Blood (20 ml) was drawn from 21 healthy and 10 hyperthyroid subjects. The abundance of GLUT isoforms on the monocyte plasma membrane was determined in the absence and presence of IGF-I (0.07, 0.14, and 0.7 nM) using flow cytometry. Anti-CD14-phycoerythrin monocional antibody was used for monocyte gating. GLUT isoforms were determined after staining the cells with specific antisera to GLUT3 and GLUT4. Results: In monocytes from the euthyroid subjects, IGF-I increased the abundance of GLUT3 and GLUT4 on the monocyte surface by 25 and 21% respectively (P!0.0005 with repeated measures ANOVA). Hyperthyroidism increased the basal monocyte surface GLUT3 and GLUT4; in these cells, IGF-I had a marginal but highly significant effect (PZ0.003, with repeated measures ANOVA) on GLUT3 (11%) and GLUT4 (10%) translocation on the plasma membrane. Conclusions: In hyperthyroidism: 1) basal abundance of GLUT3 and GLUT4 on the plasma membrane is increased and 2) the sensitivity of the recruitment of GLUT3 and GLUT4 transporters on the plasma membrane in response to IGF-I is increased. These findings may contribute to the understanding of the mechanism by which hyperthyroidism increases glucose disposal in peripheral tissues.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 65%

IGF-I increases the recruitment of GLUT4 and GLUT3 glucose transporters on cell surface in hyperthyroidism

Dimitriadis

Maratou²,

Boutati³

et al. 2008

European Journal of Endocrinology

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“…In HR, the absolute rates of insulin-stimulated glucose transport in peripheral tissues (such as muscle or adipose tissue) have generally been found to be normal or increased, in order to adapt to high energy demand (3,25). However, we have recently shown that glucose uptake in muscle in HR is indeed resistant to insulin, but this defect is masked by a marked increase in blood flow (4); this could be attributed to the dramatic decrease in intracellular pathways of insulin-stimulated glucose metabolism (such as glycogen synthesis) (25,26). In addition, tumor necrosis factor a and interleukin 6 may contribute to insulin resistance in the metabolism of both lipids and glucose in HR (27).…”

Section: Discussionmentioning

confidence: 99%

Studies of insulin resistance in patients with clinical and subclinical hyperthyroidism

Maratou

Hadjidakis

Peppa

et al. 2010

European Journal of Endocrinology

100

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Objective: Although clinical hyperthyroidism (HR) is associated with insulin resistance, the information on insulin action in subclinical hyperthyroidism (SHR) is limited. Design and methods: To investigate this, we assessed the sensitivity of glucose metabolism to insulin in vivo (by an oral glucose tolerance test) and in vitro (by measuring insulin-stimulated rates of glucose transport in isolated monocytes) in 12 euthyroid subjects (EU), 16 patients with HR, and 10 patients with SHR. Results: HR and SHR patients displayed higher postprandial glucose levels (area under the curve, AUC 0-300 32 190G1067 and 31 497G716 mg/dl min respectively) versus EU (27 119 G1156 mg/dl min, P!0.05). HR but not SHR patients displayed higher postprandial insulin levels (AUC 0-300 11 020G985 and 9565G904 mU/l min respectively) compared with EU subjects (AUC 0-300 7588G743 mU/l min, P!0.05). Homeostasis model assessment index was increased in HR and SHR patients (2.81G0.3 and 2.43G0.38 respectively) compared with EU subjects (1.27 G0.16, P!0.05), while Matsuda and Belfiore indices were decreased in HR (4.21G0.41 and 0.77G0.05 respectively, P!0.001) and SHR patients (4.47G0.33 and 0.85G0.05 respectively, P!0.05 versus EU (7.76G0.87 and 1 respectively). At 100 mU/ml insulin, i) GLUT3 levels on the monocyte plasma membrane were increased in HR (468.8G7 mean fluorescence intensity (MFI)) and SHR patients (522.2G25 MFI) compared with EU subjects (407G18 MFI, P!0.01 and P!0.05 respectively), ii) glucose transport rates in monocytes (increases from baseline) were decreased in HR patients (37.8G5%) versus EU subjects (61.26G10%, P!0.05). Conclusions: Insulin-stimulated glucose transport in isolated monocytes of patients with HR was decreased compared with EU subjects. Insulin resistance was comparable in patients with both HR and SHR.

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“…Thus, several investigations have demonstrated a stimulatory effect of T3 on insulin-stimulated glucose transport and/or phosphorylation in muscle [4,5], on the insulin-sensitive muscle/fat glucose transporter, GLUT4 [4,6], and on glycolysis in isolated muscle [5]. Other data showed decreased insulinstimulated glucose transport and/or phosphorylation, as well as a lower rate of glycolysis in isolated muscles from hypothyroid animals, as induced by propylthiouracil (PTU) administration [5,7]. Similar findings were obtained when studying isolated adipocytes from hypothyroid patients, as these cells exhibited decreased insulin responsiveness with regard to glucose utilisation.…”

Section: Introductionmentioning

confidence: 99%

Hypothyroidism in rats decreases peripheral glucose utilisation, a defect partially corrected by central leptin infusion

et al. 2005

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Aims/hypothesis: The aims of this work were to determine the effect of hypothyroidism on insulin-stimulated glucose turnover and to unravel the potential mechanisms involved in such an effect. Methods: Hypothyroidism was induced by administration of propylthiouracil, with partial T4 substitution. Euglycaemic-hyperinsulinaemic clamps, associated with the labelled 2-deoxy-D-glucose technique for measuring tissue-specific glucose utilisation, were used. To assess a possible involvement of leptin in the modulation of glucose metabolism by hypothyroidism, leptin was infused intracerebroventricularly for 6 days. A group of leptin-infused rats was treated with rT3 to determine a potential role of T3 in mediating the leptin effects. Results: Compared with euthyroid rats, hypothyroid animals exhibited decreased overall glucose turnover and decreased glucose utilisation indices in skeletal muscle and adipose tissue. Leptinaemia in hypothyroid rats was lower while resistin mRNA expression in adipose tissue was higher than in euthyroid animals. Intracerebroventricular leptin infusion in hypothyroid rats partially restored overall, muscle and adipose tissue insulinstimulated glucose utilisation and improved the reduced glycaemic response observed during insulin tolerance tests. The leptin effects were due neither to the observed increase in plasma T3 levels nor to changes in the high adipose tissue resistin expression of hypothyroid rats. The administration of leptin to hypothyroid animals was accompanied by increased expression of muscle and adipose tissue carnitine palmitoyl transferases, decreased plasma NEFA levels and reduced muscle triglyceride content. Conclusions/interpretation: Hypothyroidism is characterised by decreased insulin responsiveness, partly mediated by an exaggerated glucose-fatty acid cycle that is partly alleviated by intracerebroventricular leptin administration.

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The effects of insulin on transport and metabolism of glucose in skeletal muscle from hyperthyroid and hypothyroid rats

Cited by 92 publications

References 35 publications

IGF-I increases the recruitment of GLUT4 and GLUT3 glucose transporters on cell surface in hyperthyroidism

IGF-I increases the recruitment of GLUT4 and GLUT3 glucose transporters on cell surface in hyperthyroidism

Studies of insulin resistance in patients with clinical and subclinical hyperthyroidism

Hypothyroidism in rats decreases peripheral glucose utilisation, a defect partially corrected by central leptin infusion

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