Ghrelin signalling in <i>β</i>‐cells regulates insulin secretion and blood glucose

Yada, Toshihiko; Boldbaatar, Damdindorj; Rita, Rauza Sukma; Kurashina, Tomoyuki; Ando, Akihiko; Taguchi, Masanobu; Koizumi, Masaru; Sone, Hideyuki; Nakata, Masao; Kakei, Masafumi; Dezaki, Katsuya

doi:10.1111/dom.12344

Cited by 67 publications

(52 citation statements)

References 45 publications

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“…Several studies have reported that H. pylori seropositivity was associated with different hormones [2,[8][9][10], most of which were involved in glucose metabolism directly or indirectly [11][12][13][14][15][16][17]. To our knowledge, at least three hormones supported our results, including gastrin, leptin and ghrelin.…”

Section: Discussionsupporting

confidence: 85%

“…Leptin has been reported to reduce hyperglycaemia in rodent models of type 1 diabetes and has recently been shown to normalise fasting plasma glucose concentrations in a rodent model of polygenic obesity and type 2 diabetes [14]. In contrast, ghrelin has been shown to upregulate systemic glucose levels in both humans and rodents [16]. Thus, studies reporting elevated gastrin and leptin and decreased ghrelin levels in individuals infected with H. pylori support our findings.…”

Section: Discussionsupporting

confidence: 84%

“…A large number of published studies, reviews and book chapters have reported associations between H. pylori infection and serum or gastric concentrations of various hormones [2,[8][9][10], such as insulin, glucagon-like peptide 1, leptin, ghrelin, gastrin and somatostatin, some of which are involved in glucose metabolism directly or indirectly [11][12][13][14][15][16][17]. These studies provided the preliminary pathophysiological evidence for the potential connection between H. pylori infection and diabetes risk.…”

Section: Introductionmentioning

confidence: 95%

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The association between Helicobacter pylori seropositivity and risk of new-onset diabetes: a prospective cohort study

Zhou

Liu

et al. 2017

Diabetologia

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Aims/hypothesis Previous studies have suggested a possible connection between Helicobacter pylori (H. pylori) infection and diabetes risk. However, prospective studies examining direct associations between these two factors are relatively lacking. In this prospective cohort study, we aimed to evaluate the association between H. pylori infection and risk of developing diabetes. Methods We performed a population-based prospective study, recruiting participants aged 45-74 years and without diabetes from the Chinese Multi-provincial Cohort Study in 2002, with a 10 year follow-up to investigate development of diabetes. H. pylori serostatus was determined by measuring serum H. pylori antibodies. H. pylori seropositivity was defined as the antibody concentration ≥ 10 U/ml. To examine the association between H. pylori seropositivity and diabetes risk, modified Poisson regression was performed. Results Of 2085 participants without diabetes, 1208 (57.9%) were H. pylori seropositive in 2002. After multivariate adjustment of possible diabetes risk factors, H. pylori seropositivity was associated with lower risk of diabetes (RR 0.78 [95% CI 0.63, 0.97], p = 0.022). Of the 1275 participants with H. pylori antibody measurements in both 2002 and 2007, 677 (53.1%) were persistently seropositive. A lower risk of diabetes was also observed in participants with persistent H. pylori seropositivity (RR 0.61 [95% CI 0.41, 0.93], p = 0.020), compared with those persistently seronegative. Conclusions/interpretation H. pylori seropositivity was associated with lower risk of diabetes in this prospective cohort study. Extrapolation of these results and the mechanism underlying the observed association require further investigation.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 95%

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The association between Helicobacter pylori seropositivity and risk of new-onset diabetes: a prospective cohort study

Zhou

Liu

et al. 2017

Diabetologia

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“…Although the chronic hypothyroid mice in our study did not produce elevated circulating ghrelin levels, there was clearly an effect of thyroid hormone deficiency to induce ghrelin locally within hESC-derived grafts. Pancreatic ghrelin serves as a local regulator of insulin release even though it may not contribute to the circulating ghrelin levels (20). Therefore, ghrelin may be acting in a paracrine manner to impair insulin secretion in the hESCderived grafts from chronic hypothyroid mice.…”

Section: Discussionmentioning

confidence: 99%

Hypothyroidism Impairs Human Stem Cell–Derived Pancreatic Progenitor Cell Maturation in Mice

et al. 2016

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Pancreatic progenitors derived from human embryonic stem cells (hESCs) are a potential source of transplantable cells for treating diabetes and are currently being tested in clinical trials. Yet, how the milieu of pancreatic progenitor cells, including exposure to different factors after transplant, may influence their maturation remains unclear. Here, we examined the effect of thyroid dysregulation on the development of hESC-derived progenitor cells in vivo. Hypothyroidism was generated in SCID-beige mice using an iodine-deficient diet containing 0.15% propyl-2-thiouracil, and hyperthyroidism was generated by addition of L-thyroxine (T4) to drinking water. All mice received macroencapsulated hESC-derived progenitor cells, and thyroid dysfunction was maintained for the duration of the study (“chronic”) or for 4 weeks posttransplant (“acute”). Acute hyperthyroidism did not affect graft function, but acute hypothyroidism transiently impaired human C-peptide secretion at 16 weeks posttransplant. Chronic hypothyroidism resulted in severely blunted basal human C-peptide secretion, impaired glucose-stimulated insulin secretion, and elevated plasma glucagon levels. Grafts from chronic hypothyroid mice contained fewer β-cells, heterogenous MAFA expression, and increased glucagon+ and ghrelin+ cells compared to grafts from euthyroid mice. Taken together, these data suggest that long-term thyroid hormone deficiency may drive the differentiation of human pancreatic progenitor cells toward α- and ε-cell lineages at the expense of β-cell formation.

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“…This peptide is comprised of 28 amino acids with the unique feature of an n-octanoylated residue (serine-3) (Kojima et al, 1999). The numerous and diverse physiological roles of ghrelin consist of the stimulated pituitary release of growth hormone, increased food intake, mediation of energy homeostasis, enhanced gastrointestinal motility, and the regulation of systemic insulin levels and glycaemia (Kojima et al, 1999;Kirchner et al, 2012;Yada et al, 2014;Perello & Dickson, 2015;Alamri et al, 2016). To date, molecular biological studies have revealed that ghrelin is widely conserved in both mammals and nonmammals (Kojima et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Distribution and Morphology of Ghrelin-Immunopositive Cells in the Liver of the African Ostrich

Wang

Zhang

et al. 2017

Int. J. Morphol.

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JIA-XIANG, W.; PENG, L.; XIAO-TING, Z. & LI-XUN, Y.Distribution and morphology of ghrelin-immunopositive cells in the liver of the african ostrich. Int. J. Morphol., 35(4):1285Morphol., 35(4): -1290Morphol., 35(4): , 2017. SUMMARY:Ghrelin is the endogenous ligand for the growth hormone secretagogue receptor, and has been found in the liver of multiple vertebrates. While ghrelin has been identified in the gastrointestinal tract of African ostrich chicks, little is known regarding its distribution in the liver of the African ostrich. In the present study, the distribution and morphological characteristics of ghrelin-immunopositive (ghrelin-ip) cells in the liver of the African ostrich were investigated using immunohistochemistry. Our results indicate that the liver is divided into two sections: the capsule and the parenchyma, which comprises hepatic lobules and the hepatic portal area. The hepatic lobules include the central vein, hepatocellular cord, and the hepatic sinusoid. The hepatocellular cord is composed of hepatocytes, and Macrophagocytus stellatus (Kupffer cells) as well as endothelial cells reside within the hepatic sinusoid. ghrelin-ip cells were detected among both the Macrophagocytus stellatus and endothelial cells of the hepatic sinusoid in the African ostrich liver. In contrast, no ghrelinip cells were located within the hepatocytes or the hepatic portal area. These results clearly demonstrated the presence of ghrelin-ip cells in the liver of the African ostrich. Therefore, ghrelin may have a physiological function in the liver of the African ostrich.

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Ghrelin signalling in β‐cells regulates insulin secretion and blood glucose

Cited by 67 publications

References 45 publications

The association between Helicobacter pylori seropositivity and risk of new-onset diabetes: a prospective cohort study

The association between Helicobacter pylori seropositivity and risk of new-onset diabetes: a prospective cohort study

Hypothyroidism Impairs Human Stem Cell–Derived Pancreatic Progenitor Cell Maturation in Mice

Distribution and Morphology of Ghrelin-Immunopositive Cells in the Liver of the African Ostrich

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