Effects of insulin, leptin, and glucagon on ghrelin secretion from isolated perfused rat stomach

Kamegai, Jun; Tamura, Hideki; Shimizu, Takako; Ishii, Shinya; Sugihara, Hitoshi; Oikawa, Shinichi

doi:10.1016/j.regpep.2004.01.012

Cited by 112 publications

(101 citation statements)

References 30 publications

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“…Our data show that insulin and leptin suppressed ghrelin mRNA levels in human visceral fat cells. In this regard, perfusion of the rat stomach with insulin or leptin induced a dosedependent inhibition of ghrelin release [38] and infusion of insulin at physiological doses throughout prolonged euglycaemic-hyperinsulinaemic clamps significantly decreased desacyl ghrelin in healthy participants and pregnant women with type 2 diabetes [13,39]. Our results also show that insulin increases GOAT transcript levels in human fat cells.…”

Section: Discussionsupporting

confidence: 56%

The ghrelin O-acyltransferase–ghrelin system reduces TNF-α-induced apoptosis and autophagy in human visceral adipocytes

et al. 2012

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Aims/hypothesis Proinflammatory and proapoptotic cytokines such as TNF-α are upregulated in human obesity. We evaluated the association between ghrelin isoforms (acylated and desacyl ghrelin) and TNF-α in obesity and obesity-associated type 2 diabetes, as well as the potential role of ghrelin in the control of apoptosis and autophagy in human adipocytes. Methods Plasma concentrations of the ghrelin isoforms and TNF-α were measured in 194 participants. Ghrelin and ghrelin O-acyltransferase (GOAT) levels were analysed by western-blot, immunohistochemistry and real-time PCR in 53 biopsies of human omental adipose tissue. We also determined the effect of acylated and desacyl ghrelin (10 to 1,000 pmol/l) on TNF-α-induced apoptosis and autophagy-related molecules in omental adipocytes. Results Circulating concentrations of acylated ghrelin and TNF-α were increased, whereas desacyl ghrelin levels were decreased in obesity-associated type 2 diabetes. Ghrelin and GOAT were produced in omental and subcutaneous adipose tissue. Visceral adipose tissue from obese patients with type 2 diabetes showed higher levels of GOAT, increased adipocyte apoptosis and increased expression of the autophagyrelated genes ATG5, BECN1 and ATG7. In differentiating Diabetologia (2012) human omental adipocytes, incubation with acylated and desacyl ghrelin reduced TNF-α-induced activation of caspase-8 and caspase-3, and cell death. In addition, acylated ghrelin reduced the basal expression of the autophagyrelated genes ATG5 and ATG7, while desacyl ghrelin inhibited the TNF-α-induced increase of ATG5, BECN1 and ATG7 expression. Conclusions/interpretation Apoptosis and autophagy are upregulated in human visceral adipose tissue of patients with type 2 diabetes. Acylated and desacyl ghrelin reduce TNF-α-induced apoptosis and autophagy in human visceral adipocytes.

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Section: Discussionsupporting

confidence: 56%

The ghrelin O-acyltransferase–ghrelin system reduces TNF-α-induced apoptosis and autophagy in human visceral adipocytes

et al. 2012

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“…Reduced plasma insulin levels in the animals maintained on the high protein low carbohydrate diet relative to the chow fed animals are likely due to a lack of dietary carbohydrate such that insulin release is not stimulated, in addition to overall weight loss. It has been demonstrated that plasma insulin and ghrelin levels have an inverse relationship such that when insulin levels rise, ghrelin levels fall [26][27][28]. Plasma ghrelin levels also fluctuate depending upon both short-and long-term nutritional status.…”

Section: Discussionmentioning

confidence: 99%

Energy balance and hypothalamic effects of a high-protein/low-carbohydrate diet

Kinzig¹,

Hargrave²,

Hyun

et al. 2007

Physiology & Behavior

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Diets high in fat or protein and extremely low in carbohydrate are frequently reported to result in weight loss in humans. We previously reported that rats maintained on a low carbohydrate-high fat diet (LC-HF) consumed similar kcals/day as chow (CH)-fed rats and did not differ in body weight after 7 weeks. LC-HF rats had a 45% decrease in POMC expression in the ARC, decreased plasma insulin, and increased plasma leptin and ghrelin. In the present study we assessed the effects of a low carbohydrate-high protein diet (HP: 30% fat, 65% protein, and 5% CHO) on body weight, caloric intake, plasma hormone levels and hypothalamic gene expression. Male rats (n=16) were maintained on CH or HP for 4 weeks. HP rats gained significantly less weight than CH rats (73.4 +/− 9.4 and 125.0 +/− 8.2 g) and consumed significantly less kcals/day (94.8 +/− 1.5 and 123.6 +/− 1.1). Insulin was significantly reduced in HP rats (HP: 1.8 +/− 0.6 vs. CH: 4.12 +/− 0.8 ng/ml), there were no differences between groups in plasma leptin and plasma ghrelin was significantly elevated in HP rats (HP: 127.5 +/− 45 vs. CH: 76.9 +/− 8 pg/ml). Maintenance on HP resulted in significantly increased ARC POMC (HP: 121 +/− 10.0 vs. 100 +/− 5.9) and DMH NPY (HP: 297 +/− 82.1 vs. CH: 100+/− 37.7) expression compared to CH controls. These data suggest that the macronutrient content of diets differentially influences hypothalamic gene expression in ways that can affect overall intake.

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“…One factor may be insulin, since it is down-regulated in response to fasting and up-regulated in states of obesity and has previously been reported to negatively regulate the synthesis and release of ghrelin from the stomach (Kamegai et al 2004). Therefore, we sought to determine if insulin could also have a direct inhibitory effect on PIT and HPT ghrelin expression.…”

Section: Metabolic Regulation Of the In2-ghrelin Variantmentioning

confidence: 99%

Identification of a mouse ghrelin gene transcript that contains intron 2 and is regulated in the pituitary and hypothalamus in response to metabolic stress

Kineman

Gahete²,

Luque³

2007

Journal of Molecular Endocrinology

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The mouse ghrelin gene contains 5 exons (Ex), with Ex2-Ex5 encoding a 117 amino acid preproprotein that is processed to yield a 28 amino acid mature peptide. The current study examined if pituitary (PIT) and hypothalamus (HPT) ghrelin expression is up-regulated in response to fasting and down-regulated in obesity, as previously reported in the stomach. In the process of establishing a quantitative real-time RT-PCR system to accurately assess the changes in PIT and HPT ghrelin mRNA levels, we observed that primer sets located in Ex2 and Ex3 amplified a ghrelin transcript that contained the entire intron 2 (In2). Size and sequence analysis of RT-PCR products using multiple primer sets located throughout the ghrelin gene suggested that the In2-ghrelin variant contains Ex2 and Ex3, but lacks Ex1, Ex4, and Ex5. In2-ghrelin variant mRNA was not detected in stomach extracts, while expression levels were 10-and 50-fold greater than that of the native ghrelin transcript in the PIT and HPT respectively. In2-ghrelin variant mRNA levels increased in the PIT after 24 h fasting and decreased in the HPT and PIT of diet-induced obese mice. These changes may be due to the changes in circulating insulin or IGF-I, since both decreased In2-ghrelin variant expression in a mouse HPT cell line (N6) and in primary mouse PIT cell cultures. The fact that In2-ghrelin variant mRNA levels are dependent on energy intake in the PIT and HPT suggests that this transcript may encode a peptide important in coordinating the neuroendocrine response to metabolic stress.

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Effects of insulin, leptin, and glucagon on ghrelin secretion from isolated perfused rat stomach

Cited by 112 publications

References 30 publications

The ghrelin O-acyltransferase–ghrelin system reduces TNF-α-induced apoptosis and autophagy in human visceral adipocytes

The ghrelin O-acyltransferase–ghrelin system reduces TNF-α-induced apoptosis and autophagy in human visceral adipocytes

Energy balance and hypothalamic effects of a high-protein/low-carbohydrate diet

Identification of a mouse ghrelin gene transcript that contains intron 2 and is regulated in the pituitary and hypothalamus in response to metabolic stress

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