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Pyroglutamyl-phenylalanyl-proline amide attenuates thyrotropin-releasing hormone-stimulated insulin secretion in perifused rat islets and insulin-secreting clonal beta-cell lines.
Kulkarni, R N; Wang, Z L; Akinsanya, K O; Bennet, W M; Wang, R M; Smith, D M; Ghatei, M A; Byfield, P G; Bloom, S R.
Afiliação
  • Kulkarni RN; Francis Fraser Laboratories, Department of Metabolic Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.
Endocrinology ; 136(11): 5155-64, 1995 Nov.
Article em En | MEDLINE | ID: mdl-7588254
ABSTRACT
TRH immunoreactivity has been detected in the pancreas of man and rat and localized to the islets of Langerhans. We studied the effect of synthetic TRH and the related tripeptide pyroglutamyl-phenylalanyl-proline amide (EFP) on isolated perifused rat islets and the glucose-responsive clonal cell lines HIT-T15 and RIN5AH. TRH at 10 nM potentiated [0.5 +/- 0.1 (control) vs. 0.8 +/- 0.1 (TRH) pmol/10(6) cells per 120 min; mean +/- SEM; n = 6; P < 0.001; n = 15], whereas EFP from 1 nM upwards suppressed glucose-stimulated insulin secretion [0.8 +/- 0.1 (control) vs. 0.5 +/- 0.1 (EFP) pmol/10(6) cells per 120 min; P < 0.001; n = 12) in the cell lines. Further, EFP reversed TRH-stimulated insulin release. Similar responses were observed in perifused isolated rat islets at the tested dose of 1 microM. Gel permeation chromatography of rat adult and neonatal whole pancreas, isolated islets, and HIT cell extracts demonstrated the elution of total TRH-like immunoreactivity (t-TRH-LI) in the same position as synthetic TRH. Cation exchange analysis of the t-TRH-LI from rat adult pancreas and HIT cell extracts showed that neutral TRH-like peptides corresponding to synthetic EFP were also present. Reverse-phase fast protein liquid chromatographic analysis of t-TRH-LI in the unbound fraction of these extracts subjected to anion exchange columns, also demonstrated peaks corresponding to synthetic EFP. We conclude that TRH potentiates, whereas EFP inhibits, glucose-stimulated insulin release in isolated perifused islets and the cell lines. In addition, EFP reversed the stimulatory effect of TRH. The presence of EFP-LI in rat adult and neonatal pancreas and HIT cell extracts suggests it may contribute in the modulation of pancreatic endocrine function.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oligopeptídeos / Ilhotas Pancreáticas / Hormônio Liberador de Tireotropina / Insulina Limite: Animals / Humans / Male Idioma: En Ano de publicação: 1995 Tipo de documento: Article
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oligopeptídeos / Ilhotas Pancreáticas / Hormônio Liberador de Tireotropina / Insulina Limite: Animals / Humans / Male Idioma: En Ano de publicação: 1995 Tipo de documento: Article