Insulin secretion control is critical for glucose homeostasis. Paracrine and autocrine molecules secreted by cells of the islet of Langerhans, as well as by intramural and autonomic neurons, control the release of different hormones that modulate insulin secretion. In pancreatic islets, the abundant presence of the granin protein VGF (nonacronymic; unrelated to VEGF) suggests that some of its proteolytically derived peptides could modulate hormone release. Thus, in the present study, we screened several VGF-derived peptides for their ability to induce insulin secretion, and we identified the VGF C-terminal peptide TLQP-62 as the most effective fragment. TLQP-62 induced a potent increase in basal insulin secretion as well as in glucose-stimulated insulin secretion in several insulinoma cell lines. We found that this peptide stimulated insulin release via increased intracellular calcium mobilization and fast expression of the insulin 1 gene. Moreover, the peripheral injection of TLQP-62 in mice improved glucose tolerance. Together, the present findings suggest that TLQP-62, acting as an endocrine, paracrine, or autocrine factor, can be considered a new, strong insulinotropic peptide that can be targeted for innovative antidiabetic drug discovery programs.

Petrocchi Passeri, P., Cero, C., Cutarelli, A., Frank, C., Severini, C., Bartolomucci, A., et al. (2015). The VGF-derived peptide TLQP-62 modulates insulin secretion and glucose homeostasis. JOURNAL OF MOLECULAR ENDOCRINOLOGY, 54(3), 227-239 [10.1530/JME-14-0313].

The VGF-derived peptide TLQP-62 modulates insulin secretion and glucose homeostasis

POSSENTI, ROBERTA
2015-01-01

Abstract

Insulin secretion control is critical for glucose homeostasis. Paracrine and autocrine molecules secreted by cells of the islet of Langerhans, as well as by intramural and autonomic neurons, control the release of different hormones that modulate insulin secretion. In pancreatic islets, the abundant presence of the granin protein VGF (nonacronymic; unrelated to VEGF) suggests that some of its proteolytically derived peptides could modulate hormone release. Thus, in the present study, we screened several VGF-derived peptides for their ability to induce insulin secretion, and we identified the VGF C-terminal peptide TLQP-62 as the most effective fragment. TLQP-62 induced a potent increase in basal insulin secretion as well as in glucose-stimulated insulin secretion in several insulinoma cell lines. We found that this peptide stimulated insulin release via increased intracellular calcium mobilization and fast expression of the insulin 1 gene. Moreover, the peripheral injection of TLQP-62 in mice improved glucose tolerance. Together, the present findings suggest that TLQP-62, acting as an endocrine, paracrine, or autocrine factor, can be considered a new, strong insulinotropic peptide that can be targeted for innovative antidiabetic drug discovery programs.
2015
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/09 - FISIOLOGIA
Settore BIO/14 - FARMACOLOGIA
English
Con Impact Factor ISI
GSIS; diabetes; intracellular calcium; neuropeptide; signaling; Animals; Calcium Signaling; Cell Line, Tumor; Cell Proliferation; Drug Evaluation, Preclinical; Gene Expression; Glucose; Glucose Intolerance; Hypoglycemic Agents; Insulin; Male; Mice; Neuropeptides; Peptides; Rats; Transcriptional Activation; Homeostasis
Petrocchi Passeri, P., Cero, C., Cutarelli, A., Frank, C., Severini, C., Bartolomucci, A., et al. (2015). The VGF-derived peptide TLQP-62 modulates insulin secretion and glucose homeostasis. JOURNAL OF MOLECULAR ENDOCRINOLOGY, 54(3), 227-239 [10.1530/JME-14-0313].
Petrocchi Passeri, P; Cero, C; Cutarelli, A; Frank, C; Severini, C; Bartolomucci, A; Possenti, R
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/185027
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