Changes induced by hypothyroidism in insulin secretion and in the properties of islet plasma membranes

Diaz, Graciela; Paladini, Alejandro C.; García, María Elisa; Gagliardino, J.J.

doi:10.3109/13813459309003922

Cited by 21 publications

(23 citation statements)

References 24 publications

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“…Taylor et al (1985) stated in thyrotoxic humans normal insulin secretion, whereas Casla et al (1993) found both slightly decreased level of insulin after 10 days treatment of rats with T 4 and its doubled concentration after 30 days. Our results are in a good agreement with many authors who stated that the insulin secretion increases after the administration of thyroid hormones (Okajima & Ui, 1978;Heise et al, 1982;Lenzen & Bailey, 1984;Diaz et al, 1993;Fickova et al, 1997). Simultaneously, we stated that T 4 treatment increases the number of both classes of insulin receptors (HAIRs and LAIRs) and in consequence insulin binding.…”

Section: Discussionsupporting

confidence: 95%

“…On the other hand, Lenzen and Bailey (1984) noticed a decreased insulin release in hypothyreosis. This same effect was obtained by Diaz et al (1993) on isolated rat islets of Langerhans. However, according to Meserve and Skibski (1986), TU produced hyperinsulinemia and reduced hyperglycaemia.…”

Section: Discussionsupporting

confidence: 82%

“…Thyroid hormones may not only affect insulin secretion from pancreatic B cells (Diaz et al, 1993) but they also modify its action in the target cells (Matthaei et al, 1995;Fickova et al, 1997). This is partially due to their influence on the processes occurring in plasma membranes (Schroeder, 1982).…”

Section: Introductionmentioning

confidence: 99%

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The Influence of Hypo- and Hyperthyreosis on Insulin Receptors and Metabolism

Maćkowiak¹,

Ginalska²,

Nowak-Strojec³

et al. 1999

Archives of Physiology and Biochemistry

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Changes in thyroid status affect metabolism not only directly, but influence it also by alterations in insulin secretion and action. Despite several investigations, these effects are, however, poorly characterised or even controversial. The aim of the studies was to investigate the effect of hyperthyreosis (HT) and hypothyreosis (HPT) on insulin binding by rat liver membranes. Some metabolic parameters reflecting insulin and thyroid hormones action were also determined. HT and HPT were developed by daily administration for 3 weeks of thyroxine (T (4) ) and thiouracil (TU), respectively. Experimental hyperthyreosis and hypothyreosis caused deep changes in metabolism. The greatest alterations were observed in body and thyroid glands weight, blood triiodothyronine (T (3) ), T (4), glucose, and insulin levels, liver glycogen amount and number of insulin receptors. HT reflected in rats in slower rate of growth and in smaller thyroid glands weight. In comparison to controls, T (4) concentration in HT was almost doubled and it was reduced by about 30% in HPT. Also, T(3), insulin and glucose levels in HT were heightened. Simultaneously, binding of insulin to liver membranes was elevated in HT and reduced in HPT. In HT the number of high affinity insulin receptors (HAIRs) and low affinity insulin receptors (LAIRs) was increased, whereas in HPT the amount of HAIRs was diminished. HT caused a drastic reduction of glycogen concentration in liver, but no changes were observed for muscle glycogen. Considering lipid metabolism, only free fatty acids (FFA) level in blood was changed (in HPT), but no differences were observed in serum concentration of triglycerides and cholesterol. Several metabolic changes observed in HT and HPT seem to be the dire ct consequence of alterations of thyroid hormone concentrations. These disturbances, together with the direct effect of HT or HPT on insulin secretion, binding and action lead, in turn, to changes in the other metabolic parameters. As a result of these disturbances the adaptive mechanisms appear. One of them is change in the number of insulin membrane receptors taking place even against the well known "down-regulation" theory.

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Section: Discussionsupporting

confidence: 95%

Section: Discussionsupporting

confidence: 82%

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The Influence of Hypo- and Hyperthyreosis on Insulin Receptors and Metabolism

Maćkowiak¹,

Ginalska²,

Nowak-Strojec³

et al. 1999

Archives of Physiology and Biochemistry

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“…In our study, we used genetically engineered ZDF rats, which exhibit progressive induction of diabetes. In normal animals, hypothyroidism is not only known to induce hypercholesterolemia and obesity, but also to diminish insulin secretion [7,8,13]. Similar to our study, serum glucose concentrations in methimazole-treated SD rats were not significantly different from controls [38].…”

Section: Discussionsupporting

confidence: 79%

Effects of Methimazole on the Onset of Type 2 Diabetes in Leptin Receptor-Deficient Rats

Hwang

Kim

et al. 2009

The Journal of Veterinary Medical Science

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We investigated the effects of methimazole, an anti-thyroid drug, on the onset of type 2 diabetes in Zucker diabetic fatty (ZDF) rats. For this, 0.03% methimazole was administered to 7-week-old, pre-diabetic ZDF rats in drinking water for 5 weeks and the animals were sacrificed at 12 weeks of age. Methimazole treatment to ZDF rats significantly reduced blood glucose levels, food intake, body weight, and serum T3 levels. Hepatocytes in ZDF-methi rats were more densely stained with eosin than those in ZDF rats because of low fat accumulation in ZDF-methi hepatocytes. The pancreatic islet in ZDF-methi rats was normal compared to that in ZDF rats. Glucagon, not insulin, immunoreactivity in ZDF-methi rats was significantly higher than that in ZDF-methi rats. These suggest that methimazole treatment may delay the onset of type 2 diabetes in leptin receptor-deficient rats and also suggests that thyroid hormones may be necessary for the onset of diabetes.

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“…We conclude that specific FAs variably influence islet function according to the extent that they activate PPARα signalling. Islets contain TRα1 and TRβ1 [67,[87][88][89] and thyroid hormone signalling is associated with impaired GSIS, despite increased islet glucose utilization and oxidation [90]. We tested the hypothesis that hyperthyroidism might influence the PPARα-led islet adaptations to dietary fat via competition by TR with PPARα for RXR.…”

Section: Pparα and Islet Functionmentioning

confidence: 99%

Role of nuclear receptors in the modulation of insulin secretion in lipid-induced insulin resistance

Sugden

Holness

2008

Biochemical Society Transactions

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In healthy individuals, a hyperbolic relationship exists between whole-body insulin-sensitivity and insulin secretion. Thus, for any difference in insulin-sensitivity, a reciprocal proportionate change occurs in insulin secretion. Such a feedback loop is evident in healthy individuals ingesting diets high in saturated fat and in late pregnancy where, despite lipid-induced insulin resistance, glucose tolerance is maintained through augmented GSIS (glucose-stimulated insulin secretion). NRs (nuclear receptors) are members of a superfamily of ligand-regulated and orphan transcription factors. On activation by a cognate ligand, many ligand-activated NRs recruit the RXR (retinoid X receptor) for heterodimer formation. Such NRs include the PPARs (peroxisome-proliferator-activated receptors), which are involved in lipid sensing and liporegulation. PPARs exert important lipid-lowering effects in vivo, thereby opposing the development of lipid-induced insulin resistance by relieving the inhibition of insulin-stimulated glucose disposal by muscle and lowering the necessity for augmented GSIS to counter lipid-induced insulin resistance. Long-chain fatty acids are proposed as natural PPAR ligands and some specific endogenous pathways of lipid metabolism are believed to generate PPAR agonists. Other NRs, e.g. the LXR (liver X receptor), which senses expansion of the metabolically active pool of cholesterol, and the FXR (farnesoid X receptor; NR1H4), which, like the LXR, is involved in sterol metabolism, also modulate systemic lipid levels and insulin-sensitivity. In this review, we discuss how these NRs impact insulin secretion via effects on the insulin-sensitivity-insulin secretion feedback loop and, in some cases, via direct effects on the islet itself. In addition, we discuss interactions between these nutrient/metabolite-responsive NRs and NRs that are central to the action of metabolically important hormones, including (i) the glucocorticoid receptor, critical for maintaining glucose homoeostasis in stress, inflammation and during fasting, and (ii) the thyroid hormone receptors, vital for maintenance of oxidative functions. We present data indicating that the RXR occupies a key role in directly modulating islet function and that its heterodimerization with at least two of its partners modulates GSIS.

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Changes induced by hypothyroidism in insulin secretion and in the properties of islet plasma membranes

Cited by 21 publications

References 24 publications

The Influence of Hypo- and Hyperthyreosis on Insulin Receptors and Metabolism

The Influence of Hypo- and Hyperthyreosis on Insulin Receptors and Metabolism

Effects of Methimazole on the Onset of Type 2 Diabetes in Leptin Receptor-Deficient Rats

Role of nuclear receptors in the modulation of insulin secretion in lipid-induced insulin resistance

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