Morphological analysis of ghrelin and its receptor distribution in the rat pancreas

Kageyama, Haruaki; Funahashi, Hiroomi; Hirayama, Masami; Takenoya, Fumiko; Kita, Tetsuro; Kato, Sachi; Sakurai, Junko; Lee, Eun Young; Inoue, Shuji; Date, Yukari; Nakazato, Masamitsu; Kangawa, Kenji; Shioda, Seiji

doi:10.1016/j.regpep.2004.08.031

Cited by 111 publications

(73 citation statements)

References 34 publications

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“…Specifically, AG plays an important role in the regulation of glucose homeostasis by inhibiting insulin release in mice, rats, and humans , Egido et al 2002, Reimer et al 2003, Granata et al 2007. AG also modulates the production/secretion of glucagon from the pancreas (Chuang et al 2011) and, indeed, it has been demonstrated that GHSR colocalizes with glucagon and insulin in rat pancreatic islets, which further indicates that the ghrelin system plays an important role in pancreatic a-and b-cells (Kageyama et al 2005). In addition, AG has been shown to be able to modulate insulin actions, as it can induce peripheral insulin resistance (Damjanovic et al 2006, Vestergaard et al 2008) without affecting hepatic insulin sensitivity (Vestergaard et al 2013).…”

Section: Posterior Pituitary Hormonesmentioning

confidence: 94%

Ghrelin gene products, receptors, and GOAT enzyme: biological and pathophysiological insight

Gahete

Rincón-Fernández

Villa-Osaba

et al. 2013

Journal of Endocrinology

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Ghrelin is a 28-amino acid acylated hormone, highly expressed in the stomach, which binds to its cognate receptor (GHSR1a) to regulate a plethora of relevant biological processes, including food intake, energy balance, hormonal secretions, learning, inflammation, etc. However, ghrelin is, in fact, the most notorious component of a complex, intricate regulatory system comprised of a growing number of alternative peptides (e.g. obestatin, unacylated ghrelin, and In1-ghrelin, etc.), known (GHSRs) and, necessarily unknown receptors, as well as modifying enzymes (e.g. ghrelin-O-acyl-transferase), which interact among them as well as with other regulatory systems in order to tightly modulate key (patho)-physiological processes. This multiplicity of functions and versatility of the ghrelin system arise from a dual, genetic and functional, complexity. Importantly, a growing body of evidence suggests that dysregulation in some of the components of the ghrelin system can lead to or influence the development and/or progression of highly concerning pathologies such as endocrine-related tumors, inflammatory/cardiovascular diseases, and neurodegeneration, wherein these altered components could be used as diagnostic, prognostic, or therapeutic targets. In this context, the aim of this review is to integrate and comprehensively analyze the multiple components and functions of the ghrelin system described to date in order to define and understand its biological and (patho)-physiological significance.

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Section: Posterior Pituitary Hormonesmentioning

confidence: 94%

Ghrelin gene products, receptors, and GOAT enzyme: biological and pathophysiological insight

Gahete

Rincón-Fernández

Villa-Osaba

et al. 2013

Journal of Endocrinology

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“…Blood ghrelin and insulin concentration fluctuate reciprocally before and after feeding (Cummings et al 2001). Growth hormone (GH) secretagogue receptor is detected in pancreatic B cells containing insulin (Kageyama et al 2005), suggesting that ghrelin plays a role in regulating insulin secretion in the pancreas. Inconsistent results have been reported in the effects of ghrelin administration on insulin secretion.…”

Section: Introductionmentioning

confidence: 99%

Ghrelin enhances glucose-induced insulin secretion in scheduled meal-fed sheep

Takahashi

Kurose

Kobayashi

et al. 2006

Journal of Endocrinology

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The purpose of this study was to investigate the effects of physiologic levels of ghrelin on insulin secretion and insulin sensitivity (glucose disposal) in scheduled fedsheep, using the hyperglycemic clamp and hyperinsulinemic euglycemic clamp respectively. Twelve castrated Suffolk rams (69·8 0·6 kg) were conditioned to be fed alfalfa hay cubes (2% of body weight) once a day. Three hours after the feeding, synthetic ovine ghrelin was intravenously administered to the animals at a rate of 0·025 and 0·05 µg/kg body weight (BW) per min for 3 h. Concomitantly, the hyperglycemic clamp or the hyperinsulinemic euglycemic clamp was carried out. In the hyperglycemic clamp, a target glucose concentration was clamped at 100 mg/100 ml above the initial level. In the hyperinsulinemic euglycemic clamp, insulin was intravenously administered to the animals for 3 h at a rate of 2 mU/kg BW per min. Basal glucose concentrations (44 1 mg/dl) were maintained by variably infusing 100 mg/dl glucose solution. In both clamps, plasma ghrelin concentrations were dose-dependently elevated and maintained at a constant level within the physiologic range. Ghrelin infusions induced a significant (ANOVA; P<0·01) increase in plasma GH concentrations. In the hyperglycemic clamp, plasma insulin levels were increased by glucose infusion and were significantly (P<0·05) greater in ghrelin-infused animals. In the hyperinsulinemic euglycemic clamp, glucose infusion rate, an index of insulin sensitivity, was not affected by ghrelin infusion. In conclusion, the present study has demonstrated for the first time that ghrelin enhances glucose-induced insulin secretion in the ruminant animal.

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“…Ghrelin, which is mainly produced by the gastric fundus, can inhibit insulin sensitivity and secretion. [26][27][28] Current studies support that decreased ghrelin levels are linked to improved insulin sensitivity. 26,27 In the SG/MJIB and SG groups, the decreased ghrelin level was accompanied by a decreased blood glucose level, which provides evidence for the ghrelin hypothesis.…”

Section: Discussionmentioning

confidence: 99%

“…[26][27][28] Current studies support that decreased ghrelin levels are linked to improved insulin sensitivity. 26,27 In the SG/MJIB and SG groups, the decreased ghrelin level was accompanied by a decreased blood glucose level, which provides evidence for the ghrelin hypothesis. In contrast, the elevation of glucose-stimulated GLP-1 levels after the SG/MJIB and SG surgeries provides further evidence for the hindgut hypothesis, which proposed that the rapid delivery of undigested nutrients to the distal bowel upregulated the production of L-cell derivatives, such as GLP-1.…”

mentioning

confidence: 99%

Sleeve Gastrectomy With Modified Jejunoileal Bypass Model in Goto-Kakizaki Rats

Zhu

Yang

Wang³

et al. 2016

International Surgery

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The objective of this study was to develop a nonobese diabetic rat model for sleeve gastrectomy with modified jejunoileal bypass (SG/MJIB) and to investigate its effectiveness and safety for inducing diabetic control. Thirty-five 13-week-old male Goto-Kakizaki rats were randomly assigned to the pair-fed to sham-operated SG/MJIB (PFSO-SG/MJIB), SG/MJIB, PFSO-SG, SG, and control groups. The experimental period was 16 weeks postoperatively. Body weight; food intake; glycemic control outcomes; and ghrelin, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide, and insulin levels were measured. The operated and PFSO groups showed significant weight loss 4 weeks postoperatively compared with the controls. The SG/MJIB and SG groups exhibited a significant improvement in oral glucose tolerance and insulin tolerance compared with the PFSO and control groups. The improved effects in the SG/MJIB group were better than those in the SG group. The SG/MJIB and SG groups showed decreased fasting ghrelin levels and increased levels of GLP-1 secretion 2 and 16 weeks postoperatively. Compared with the SG group, only the SG/MJIB group showed higher glucose-stimulated GLP-1 levels and significantly improved insulin secretion. SG/MJIB may be an effective, steady hypoglycemic surgical model, showing better diabetic control than SG. The hindgut may play a direct role in ameliorating glucose homeostasis. More than 90% of patients with diabetes have type 2 diabetes mellitus (T2DM). Even with strict hyperglycemia control, evidence for reducing complications related to T2DM has been reported 2 ; nevertheless, current therapies, such as diet, exercise, behavior modification, oral hypoglycemic agents, and insulin, can rarely help patients return 3 Recent data proved that the most reliable treatment for the long-term management of T2DM is surgical intervention.4-6 Surgical techniques for T2DM treatment are based on intake restriction, malabsorption, or both of these. However, none of the currently performed operations can provide unanimous treatment effects or a clear therapeutic mechanism. 7,8 Among the operations performed, adjustable gastric banding achieves hypoglycemia mainly through a limited food intake. Although this surgical method is relatively safe, the glycemic regulatory effect is far from satisfactory; complications, such as intragastric erosion or band slippage, may occur 9 ; and the reoperation rate may be .10%.10 Jejunoileal bypass (JIB) has been the most effective T2DM treatment 11 ; however, because of its severe complications, JIB has been abandoned by most surgeons. 12 Other procedures that combine gastritis and malabsorption, such as Roux-en-Y bypass, exclude most parts of the stomach, making this organ and the biliary ducts inaccessible to the usual endoscopic examinations, 13,14 which is not very suitable in high-risk patients. 15Recently, sleeve gastrectomy (SG) was reported with a hypoglycemic effect similar to that of Rouxen-Y bypass. 4 However, the use of SG cannot explain the mechanism of T2DM...

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Morphological analysis of ghrelin and its receptor distribution in the rat pancreas

Cited by 111 publications

References 34 publications

Ghrelin gene products, receptors, and GOAT enzyme: biological and pathophysiological insight

Ghrelin gene products, receptors, and GOAT enzyme: biological and pathophysiological insight

Ghrelin enhances glucose-induced insulin secretion in scheduled meal-fed sheep

Sleeve Gastrectomy With Modified Jejunoileal Bypass Model in Goto-Kakizaki Rats

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