Role of plasma insulin concentration in regulating glucose and lipid metabolism in lean and obese Zucker rats

Noshiro, Osamu; Hirayama, Reiko; Shimaya, Akiyoshi; Yoneta, Takashi; Niigata, Kunihiro; Shikama, Hisataka

doi:10.1038/sj.ijo.0800375

Cited by 14 publications

(7 citation statements)

References 21 publications

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“…In contrast to the marked hypoglycaemic action of YM268 in obese Zucker rats, YM268 like other insulin sensitizers did not cause hypoglycaemia in lean Zucker rats (35). However, immunoblot analyses in this study revealed that the GLUT4 content of adipose tissue in lean Zucker rats was much higher than in obese rats after YM268 treatment.…”

Section: Pm-glut4 Ratio (%)contrasting

confidence: 85%

Insulin sensitizer YM268 ameliorates insulin resistance by normalizing the decreased content of GLUT4 in adipose tissue of obese Zucker rats

Shimaya¹,

Noshiro²,

Hirayama³

et al. 1997

European Journal of Endocrinology

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Genetically obese Zucker rats exhibit mild hyperglycaemia and hyperinsulinaemia suggesting the existence of peripheral insulin resistance. We have examined the effects of YM268, an analogue of thiazolidinedione, on the content and translocation of a glucose transporter (GLUT4) in epididymal adipose tissue in 11-week-old obese and lean Zucker rats. The administration of YM268 at a dose of 10 mg/kg for 2 weeks ameliorated hyperglycaemia, hyperinsulinaemia, and impaired glucose tolerance after glucose load in obese rats. The GLUT4 content per fat pad in obese rats was reduced to 36% of that in lean littermates. Obese rats treated with YM268 increased GLUT4 concentrations in their fat pads from a basal value of 36% up to 191% of the level in lean rats. Furthermore, in adipocytes prepared from obese rats, an increase in the ratio of GLUT4 in plasma membrane to the total amount of GLUT4 (PM-GLUT4 ratio) induced by the submaximal concentration of insulin (0.3 nmol/l) was significantly attenuated compared with that in lean rats. But the maximum effect of insulin (3 nmol/l) was not attenuated. Meanwhile, YM268 had no significant effect on the attenuated PM-GLUT4 ratio in response to insulin in obese rats. These data suggested that one of the mechanisms by which YM268 improved insulin resistance in obese Zucker rats was to normalize the decreased GLUT4 content in the adipose tissue. European Journal of Endocrinology 137 693-700

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Section: Pm-glut4 Ratio (%)contrasting

confidence: 85%

Insulin sensitizer YM268 ameliorates insulin resistance by normalizing the decreased content of GLUT4 in adipose tissue of obese Zucker rats

Shimaya¹,

Noshiro²,

Hirayama³

et al. 1997

European Journal of Endocrinology

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“…Free fatty acids are released into the circulation, in response to this negative energy balance, may reduce peripheral tissue insulin sensitivity (Van Epps‐Fung et al., 1997; Pires et al., 2007). The adverse effect of elevated NEFA concentration on peripheral tissue insulin sensitivity has been observed to be more pronounced in obese rats than in normal rats (Noshiro et al., 1997), as well as in p.p. cows that were overfed prepartum and calved overconditioned [body condition score (BCS)>4] compared with thinner cows (Holtenius et al., 2003).…”

Section: Introductionmentioning

confidence: 99%

ORIGINAL ARTICLE: Gene expression of tumour necrosis factor and insulin signalling-related factors in subcutaneous adipose tissue during the dry period and in early lactation in dairy cows

Sadri

Bruckmaier

Rahmani

et al. 2010

Journal of Animal Physiology and Animal Nutrition

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Summary Gene expression of adipose factors, which may be part of the mechanisms that underlie insulin sensitivity, were studied in dairy cows around parturition. Subcutaneous fat biopsies and blood samples were taken from 27 dairy cows in week 8 antepartum (a.p.), on day 1 postpartum (p.p.) and in week 5 p.p. In the adipose tissue samples, mRNA was quantified by real‐time reverse transcription polymerase chain reaction for tumour necrosis factor alpha (TNFα), insulin‐independent glucose transporter (GLUT1), insulin‐responsive glucose transporter (GLUT4), insulin receptor, insulin receptor substrate 1 (IRS1), insulin receptor substrate 2 (IRS2), regulatory subunit of phosphatidylinositol‐3 kinase (p85) and catalytic subunit of phosphatidylinositol‐3 kinase. Blood plasma was assayed for concentrations of glucose, β‐hydroxybutyric acid, non‐esterified fatty acids (NEFA) and insulin. Plasma parameters followed a pattern typically observed in dairy cows. Gene expression changes were observed, but there were no changes in TNFα concentrations, which may indicate its local involvement in catabolic adaptation of adipose tissue. Changes in GLUT4 and GLUT1 mRNA abundance may reflect their involvement in reduced insulin sensitivity and in sparing glucose for milk synthesis in early lactation. Unchanged gene expression of IRS1, IRS2 and p85 over time may imply a lack of their involvement in terms of insulin sensitivity dynamics. Alternatively, it may indicate that post‐transcriptional modifications of these factors came into play and may have concealed an involvement.

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“…Moreover, hormones such as insulin, glucagon, and dexamethasone play a critical role in the liver during glucose homeostasis with a very high sensitivity at a low concentration (pM–nM level) in vivo (Allan and Titheradge, 1984; Noshiro et al, 1997). Although hepatocyte monolayer has been utilized for studying the hormonal response in vitro (Hermsdorf et al, 1999), the effects of hormone on glucose metabolism were not consistent with in vivo and even contradictory with varying incubation conditions (time, medium ingredient etc.)…”

Section: Discussionmentioning

confidence: 99%

A novel 3D liver organoid system for elucidation of hepatic glucose metabolism

Lü

Zhang

Shen

et al. 2011

Biotech & Bioengineering

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Hepatic glucose metabolism is a key player in diseases such as obesity and diabetes as well as in antihyperglycemic drugs screening. Hepatocytes culture in two-dimensional configurations is limited in vitro model for hepatocytes to function properly, while truly practical platforms to perform three-dimensional (3D) culture are unavailable. In this work, we present a practical organoid culture method of hepatocytes for elucidation of glucose metabolism under nominal and stress conditions. Employing this new method of culturing cells within a hollow fiber reactor, hepatocytes were observed to self-assemble into 3D spherical organoids with preservation of tight junctions and display increased liver-specific functions. Compared to both monolayer culture and sandwich culture, the hepatocyte organoids displayed higher intracellular glycogen content, glucose consumption, and gluconeogenesis and approached the in vivo values, as also confirmed by gene expression of key enzymes. Moreover, hepatocyte organoids demonstrated more realistic sensitivity to hormonal challenges with insulin, glucagon, and dexamethasone. Finally, the exposure to high glucose demonstrated toxicities including alteration of mitochondrial membrane potential, lipid accumulation, and reactive oxygen species formation, similar to the in vivo responses, which was not captured by monolayer cultures. Collectively, hepatocyte organoids mimicked the in vivo functions better than hepatocyte monolayer and sandwich cultures, suggesting suitability for applications such as antihyperglycemic drugs screening.

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Role of plasma insulin concentration in regulating glucose and lipid metabolism in lean and obese Zucker rats

Cited by 14 publications

References 21 publications

Insulin sensitizer YM268 ameliorates insulin resistance by normalizing the decreased content of GLUT4 in adipose tissue of obese Zucker rats

Insulin sensitizer YM268 ameliorates insulin resistance by normalizing the decreased content of GLUT4 in adipose tissue of obese Zucker rats

ORIGINAL ARTICLE: Gene expression of tumour necrosis factor and insulin signalling-related factors in subcutaneous adipose tissue during the dry period and in early lactation in dairy cows

A novel 3D liver organoid system for elucidation of hepatic glucose metabolism

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