Ghrelin Is Present in Pancreatic α-Cells of Humans and Rats and Stimulates Insulin Secretion

Date, Yukari; Nakazato, Masamitsu; Hashiguchi, Suzuko; Dezaki, Katsuya; Mondal, Muhtashan S.; Hosoda, Hiroshi; Kojima, Masayasu; Kangawa, Kenji; Arima, Terukatsu; Matsuo, Hisayuki; Yada, Toshihiko; Matsukura, Shigeru

doi:10.2337/diabetes.51.1.124

Cited by 505 publications

(390 citation statements)

References 30 publications

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“…Second, epsilon cells do not produce other pancreatic hormones (insulin, glucagon, somatostatin) at any time during development. Date et al [11] presented data indicating that ghrelin is co-localised with glucagon in adult human and rat pancreas, whereas results from Volante et al [12] indicated that ghrelin is co-localised with insulin in human. We were not able to confirm either of these results; instead, our data indicate that through to adult life ghrelin peptide production is confined to a distinct cell type [4,5,13,21].…”

Section: Discussionmentioning

confidence: 99%

“…The origin of epsilon cells in the rodent and human pancreas remains controversial. Ghrelin has variably been reported to be present in alpha cells in rats and humans [11], in beta cells in humans [12] or in separate cell types [4,13,14]. In human and rodent pancreases of neonates and adults, a few epsilon cells remain visible in marginal areas of the islets [4,5,13].…”

Section: Introductionmentioning

confidence: 99%

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Ghrelin-producing epsilon cells in the developing and adult human pancreas

Mercalli²,

et al. 2008

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Aims/hypothesis While the mechanisms of specification and the reciprocal relationships of the four types of endocrine cell (alpha, beta, delta and pancreatic polypeptide cells) within the human endocrine pancreas are well described in adults and during fetal development, ghrelin-immunoreactive cells (epsilon cells) remain poorly understood. Methods We studied epsilon cells in 24 human fetal pancreases between 11 and 39 weeks of development and in 32 pancreases from adult organ donors. Results We observed single epsilon cells scattered in primitive exocrine tissue from gestational week 13 in developing pancreas. Later in the developmental process, epsilon cells started to aggregate into clusters. From gestational week 21, epsilon cells were observed located around developing islets, forming an almost continuous layer at the peripheral rim of the islets. They remain localised on the mantle of the islets, although at different amounts, in the adult pancreas. Coproduction of ghrelin with insulin, glucagon or somatostatin was not detected during fetal development. Co-production with pancreatic polypeptide was evident sporadically. Epsilon cells co-produced NK2 homeobox 2 and ISL LIM homeobox 1, but not NK6 homeobox 1 and paired box 6. A quantitative analysis was performed in the adult pancreas: there was an average of 1.17+1.17 epsilon cells per islet, the relative epsilon cell volume was 0.14+0.16% and the epsilon cell mass was 0.13+0.15 g. Neither sex nor age affected the epsilon cell mass, although there was a significant inverse correlation with BMI. Conclusions/interpretation During fetal development epsilon cells show an ontogenetic and morphogenetic pattern that is distinct from that of alpha and beta cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ghrelin-producing epsilon cells in the developing and adult human pancreas

Mercalli²,

et al. 2008

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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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“…The onset of insulin resistance and compensatory hyperinsulinemia in obesity is probably the reason for the suppression of ghrelin levels (13). Ghrelin has been characterized in earlier studies as an enhancer of insulin secretion (14,15), while more recent studies with mice have shown that the antagonism of its effects could promote the secretion of insulin and prevent glucose intolerance induced by a high-fat diet (16,17). …”

Section: Introductionmentioning

confidence: 99%

A study on the short-term effect of cafeteria diet and pioglitazone on insulin resistance and serum levels of adiponectin and ghrelin

Colombo¹,

Bazzo²,

Nogueira³

et al. 2012

Braz J Med Biol Res

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The interaction between ghrelin and adiponectin is still controversial. We investigated the effect of cafeteria diet and pioglitazone on body weight, insulin resistance, and adiponectin/ghrelin levels in an experimental study on male Wistar rats. The animals were divided into four groups of 6 rats each, and received balanced chow with saline (CHOW-O) or pioglitazone (CHOW-P), or a cafeteria diet with saline (CAFE-O) or pioglitazone (CAFE-P). The chow/cafeteria diets were administered for 35 days, and saline/pioglitazone (10 mg·kg body weight−1·day−1) was added in the last 14 days prior to euthanasia. CAFE-O animals had a higher mean final weight (372.5 ± 21.01 g) than CHOW-O (317.66 ± 25.11 g, P = 0.017) and CHOW-P (322.66 ± 28.42 g, P = 0.035) animals. Serum adiponectin levels were significantly higher in CHOW-P (55.91 ± 20.62 ng/mL) than in CHOW-O (30.52 ± 6.97 ng/mL, P = 0.014) and CAFE-O (32.54 ± 9.03 ng/mL, P = 0.027) but not in CAFE-P. Higher total serum ghrelin levels were observed in CAFE-P compared to CHOW-P animals (1.65 ± 0.69 vs 0.65 ± 0.36 ng/mL, P = 0.006). Likewise, acylated ghrelin levels were higher in CAFE-P (471.52 ± 195.09 pg/mL) than in CHOW-P (193.01 ± 87.61 pg/mL, P = 0.009) and CAFE-O (259.44 ± 86.36 pg/mL, P = 0.047) animals. In conclusion, a cafeteria diet can lead to a significant weight gain. Although CAFE-P animals exhibited higher ghrelin levels, this was probably related to food deprivation rather than to a direct pharmacological effect, possibly attenuating the increase in adiponectin levels.

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Ghrelin Is Present in Pancreatic α-Cells of Humans and Rats and Stimulates Insulin Secretion

Cited by 505 publications

References 30 publications

Ghrelin-producing epsilon cells in the developing and adult human pancreas

Ghrelin-producing epsilon cells in the developing and adult human pancreas

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

A study on the short-term effect of cafeteria diet and pioglitazone on insulin resistance and serum levels of adiponectin and ghrelin

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