Ghrelin Is Present in Pancreatic α-Cells of Humans and Rats and Stimulates Insulin Secretion
- Yukari Date12,
- Masamitsu Nakazato1,
- Suzuko Hashiguchi34,
- Katsuya Dezaki3,
- Muhtashan S. Mondal1,
- Hiroshi Hosoda2,
- Masayasu Kojima2,
- Kenji Kangawa2,
- Terukatsu Arima4,
- Hisayuki Matsuo2,
- Toshihiko Yada3 and
- Shigeru Matsukura1
- 1Department of Internal Medicine, Miyazaki Medical College, Miyazaki, Japan
- 2National Cardiovascular Center Research Institute, Osaka, Japan
- 3Department of Physiology, Jichi Medical School, Tochigi, Japan
- 4Second Department of Internal Medicine, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
Abstract
Ghrelin, a novel growth hormone–releasing peptide isolated from human and rat stomach, is a 28–amino acid peptide with a posttranslational acylation modification that is indispensable for stimulating growth hormone secretion by increasing intracellular Ca2+ concentration. It also functions in the regulation of feeding behavior, energy metabolism, and gastric acid secretion and motility. Using two different antibodies against the NH2- and COOH-terminal regions of ghrelin, we studied its localization in human and rat pancreas by immunohistochemistry. Ghrelin-immunoreactive cells were identified at the periphery of pancreatic islets in both species. Ghrelin co-localized exclusively with glucagon in rat islets, indicating that it is produced in α-cells. We identified ghrelin and des-acyl ghrelin in the rat pancreas using reverse-phase high-performance liquid chromatography combined with two radioimmunoassays. We also detected mRNA encoding ghrelin and its receptor in the rat pancreatic islets. Ghrelin increased the cytosolic free Ca2+ concentration in β-cells and stimulated insulin secretion when it was added to isolated rat pancreatic islets. These findings indicate that ghrelin may regulate islet function in an endocrine and/or paracrine manner.
Footnotes
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Address correspondence and reprint requests to Masamitsu Nakazato, PhD, Third Department of Internal Medicine, Miyazaki Medical College, Kiyotake, Miyazaki 889-1692, Japan. E-mail: nakazato{at}post.miyazaki-med.ac.jp.
Received for publication 8 August 2001 and accepted in revised form 3 October 2001.
[Ca2+]i, cytosolic free Ca2+ concentration; GH, growth hormone; GHS, growth-hormone secretagogue; GHS-R, GHS receptor; ICV, intracerebroventricularly; IV, intravenously; KRB, Krebs-Ringer bicarbonate buffer; PBS, phosphate-buffered saline; RIA, radioimmunoassay; RP-HPLC, reverse-phase high-performance liquid chromatography; RT-PCR, reverse transcription–polymerase chain reaction; TFA, trifluoroacetic acid.
