Ghrelin Modulates the Downstream Molecules of Insulin Signaling in Hepatoma Cells

Morimoto, Masahiro; Okimura, Yasuhiko; Iida, Keiji; Matsumoto, Michihiro; Sowa, Hideaki; Kaji, Hidesuke; Kojima, Masayasu; Kangawa, Kenji; Chihara, Kazuo

doi:10.1074/jbc.m103898200

Cited by 260 publications

(213 citation statements)

References 33 publications

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“…Ghrelin is able to reverse the down-regulating effect of insulin on mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK), the rate limiting enzyme of gluconeogenesis (Murata et al, 2002). Ghrelin reduces glucose-stimulated insulin secretion and glucose disappearance in healthy humans (Tong et al, 2010) thus ghrelin leads to increase in blood glucose levels and impairs glucose tolerance .…”

mentioning

confidence: 99%

Ghrelin in obesity and endocrine diseases

Scerif

Goldstone

Korbonits

2011

Molecular and Cellular Endocrinology

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mentioning

confidence: 99%

Ghrelin in obesity and endocrine diseases

Scerif

Goldstone

Korbonits

2011

Molecular and Cellular Endocrinology

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“…Studies showed that ghrelin may affect insulin sensitivity by stimulating tyrosine phosphorylation of IRS-1 (Murata et al, 2002) and insulin secretion (Date et al, 2002), but increased gluconeogenesis (Murata et al, 2002) and decreased insulin release after ghrelin infusion have also been reported (Broglio et al, 2001). Ghrelin could therefore be indirectly related to insulin sensitivity via effects on energy metabolism and body weight (Meier and Gressner, 2004).…”

Section: Discussionmentioning

confidence: 99%

Effect of moderate alcohol consumption on adipokines and insulin sensitivity in lean and overweight men: a diet intervention study

et al. 2007

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Objective: Moderate alcohol consumption is associated with a decreased risk of type II diabetes. This study investigates the effect of moderate alcohol consumption on adipokines and insulin sensitivity. Subjects: Twenty healthy, lean (body mass index (BMI) 18.5-25 kg/m 2 ; n ¼ 11) or overweight (BMI427 kg/m 2 ; n ¼ 9) men (18-25 years). Methods: Three cans of beer (40 g alcohol) or alcohol-free beer daily during 3 weeks. Results: Adiponectin and ghrelin concentrations increased (Po0.01) by 11 and 8%, while acylation-stimulating protein (ASP) concentrations decreased by 12% (P ¼ 0.04) after moderate alcohol consumption. Concentrations of leptin and resistin remained unchanged. Insulin sensitivity by an oral glucose tolerance test (OGTT) was not affected by moderate alcohol consumption, but 2 h glucose concentrations were lower (P ¼ 0.01) after beer (4.570.1 mmol/l) than alcohol-free beer (4.970.1 mmol/l). Both free fatty acids and glucagon concentrations showed a stronger increase (Po0.01) after 90 min during OGTT after beer than alcohol-free beer. Changes of adiponectin were positively correlated (r ¼ 0.69, Po0.001), and changes of leptin (r ¼ À0.53, P ¼ 0.016) and ASP (r ¼ À0.43, P ¼ 0.067) were negatively correlated with changes of insulin sensitivity index. All these results did not differ between lean and overweight men. Conclusions: Moderate alcohol consumption increased adiponectin and ghrelin, while it decreased ASP concentrations both in lean and overweight men. These changes are in line with the hypothesized improvement of insulin sensitivity, but did not affect insulin sensitivity within 3 weeks of moderate alcohol consumption.

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“…A recent experiment demonstrated that only supraphysiological concentrations of insulin decrease ghrelin concentrations, whereas somatostatin causes a marked decrease in ghrelin concentrations without changes in insulin levels (34). In vitro ghrelin modulates insulin signaling in hepatoma cells, implying peripheral actions of ghrelin in glucose homeostasis as well (35).…”

Section: Discussionmentioning

confidence: 99%

Low Plasma Ghrelin Is Associated With Insulin Resistance, Hypertension, and the Prevalence of Type 2 Diabetes

et al. 2003

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Experimental studies have suggested that ghrelin plays a role in glucose homeostasis and in the regulation of blood pressure (BP). We therefore assessed the hypothesis that a low ghrelin concentration may be a risk factor for type 2 diabetes and hypertension. We also characterized the effect of the ghrelin Arg51Gln and Leu72Met mutations on ghrelin concentrations in the population-based hypertensive (n ‫؍‬ 519) and control (n ‫؍‬ 526) cohorts of our OPERA (Oulu Project Elucidating Risk of Atherosclerosis) study. The fasting plasma ghrelin concentrations of 1,040 subjects were analyzed using the radioimmunoassay method. Insulin sensitivity was assessed using the quantitative insulin sensitivity check index (QUICKI). Ghrelin concentrations were negatively associated with fasting insulin (P < 0.001), systolic (P ‫؍‬ 0.026) and diastolic BP (P ‫؍‬ 0.018), and the prevalence of type 2 diabetes (P ‫؍‬ 0.015) and insulin resistance (P < 0.001) in the multivariate models. In the control cohort, low ghrelin was associated with hypertension (BP >140/90 mmHg) (P ‫؍‬ 0.031). The subjects with the ghrelin 51Gln allele had lower ghrelin concentrations than the Arg51Arg homozygotes (P ‫؍‬ 0.001). We conclude that low ghrelin is independently associated with type 2 diabetes, insulin concentration, insulin resistance, and elevated BP. Therefore, it might have some role in the etiology of type 2 diabetes and the regulation of BP. The ghrelin Arg51Gln mutation is associated with low plasma ghrelin concentrations. Diabetes 52:2546 -2553, 2003 G hrelin is a recently discovered peptide hormone secreted mainly from the stomach (1). It has a very potent growth hormone (GH)-releasing effect both in animal models and humans (1-3). In addition, it probably has effects independent of GH secretion (4). It is a somatotrophic orexigenic adipogenic hormone that links the regulatory systems for growth and energy balance (5). The effects of ghrelin are mediated through the GH secretagogue receptor, which is widely distributed in the body (6).The role of ghrelin in glucose and insulin metabolism has been studied actively. In experimental settings, glucose administration or food intake have been shown to decrease plasma ghrelin concentrations (7-9). Studies of the effects of ghrelin on insulin secretion have shown both stimulatory (10 -12) and inhibitory effects (13,14). In human subjects, insulin infusion has been shown to decrease ghrelin concentrations (15,16), whereas parenteral administration of insulin had no effect on ghrelin concentrations (17). On contrary, administration of insulin and leptin induced the increase of ghrelin mRNA in rats (18).Ghrelin exerts beneficial hemodynamic effects in humans by reducing cardiac afterload and increasing cardiac output (19). The vasodilatory effect is possibly mediated through a GH/IGF-I/nitric oxide-independent mechanism (20).Based on these recent studies, it appears that ghrelin might have a role in glucose and insulin metabolism and it also may influence blood pressure (BP) levels. Therefore, chang...

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Ghrelin Modulates the Downstream Molecules of Insulin Signaling in Hepatoma Cells

Cited by 260 publications

References 33 publications

Ghrelin in obesity and endocrine diseases

Ghrelin in obesity and endocrine diseases

Effect of moderate alcohol consumption on adipokines and insulin sensitivity in lean and overweight men: a diet intervention study

Low Plasma Ghrelin Is Associated With Insulin Resistance, Hypertension, and the Prevalence of Type 2 Diabetes

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