The VGF-derived peptide TLQP-62 modulates insulin secretion and glucose homeostasis.
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.
Department of Medicine of SystemsUniversity of Rome Tor Vergata, Via Montpellier, 100133 Rome, ItalyInstitute of Cell Biology and NeurobiologyCNR, Rome, ItalyDepartment of Integrative Biology and PhysiologyUniversity of Minnesota, Minneapolis, Minnesota, USAIstituto Superiore di SanitàRome, ItalyEBRI FoundationRome, Italy Department of Medicine of SystemsUniversity of Rome Tor Vergata, Via Montpellier, 100133 Rome, ItalyInstitute of Cell Biology and NeurobiologyCNR, Rome, ItalyDepartment of Integrative Biology and PhysiologyUniversity of Minnesota, Minneapolis, Minnesota, USAIstituto Superiore di SanitàRome, ItalyEBRI FoundationRome, Italy.
Pamela
P
Petrocchi-Passeri
Department of Medicine of SystemsUniversity of Rome Tor Vergata, Via Montpellier, 100133 Rome, ItalyInstitute of Cell Biology and NeurobiologyCNR, Rome, ItalyDepartment of Integrative Biology and PhysiologyUniversity of Minnesota, Minneapolis, Minnesota, USAIstituto Superiore di SanitàRome, ItalyEBRI FoundationRome, Italy.
Cheryl
C
Cero
Department of Medicine of SystemsUniversity of Rome Tor Vergata, Via Montpellier, 100133 Rome, ItalyInstitute of Cell Biology and NeurobiologyCNR, Rome, ItalyDepartment of Integrative Biology and PhysiologyUniversity of Minnesota, Minneapolis, Minnesota, USAIstituto Superiore di SanitàRome, ItalyEBRI FoundationRome, Italy Department of Medicine of SystemsUniversity of Rome Tor Vergata, Via Montpellier, 100133 Rome, ItalyInstitute of Cell Biology and NeurobiologyCNR, Rome, ItalyDepartment of Integrative Biology and PhysiologyUniversity of Minnesota, Minneapolis, Minnesota, USAIstituto Superiore di SanitàRome, ItalyEBRI FoundationRome, Italy.
Alessandro
A
Cutarelli
Department of Medicine of SystemsUniversity of Rome Tor Vergata, Via Montpellier, 100133 Rome, ItalyInstitute of Cell Biology and NeurobiologyCNR, Rome, ItalyDepartment of Integrative Biology and PhysiologyUniversity of Minnesota, Minneapolis, Minnesota, USAIstituto Superiore di SanitàRome, ItalyEBRI FoundationRome, Italy.
Claudio
C
Frank
Department of Medicine of SystemsUniversity of Rome Tor Vergata, Via Montpellier, 100133 Rome, ItalyInstitute of Cell Biology and NeurobiologyCNR, Rome, ItalyDepartment of Integrative Biology and PhysiologyUniversity of Minnesota, Minneapolis, Minnesota, USAIstituto Superiore di SanitàRome, ItalyEBRI FoundationRome, Italy Department of Medicine of SystemsUniversity of Rome Tor Vergata, Via Montpellier, 100133 Rome, ItalyInstitute of Cell Biology and NeurobiologyCNR, Rome, ItalyDepartment of Integrative Biology and PhysiologyUniversity of Minnesota, Minneapolis, Minnesota, USAIstituto Superiore di SanitàRome, ItalyEBRI FoundationRome, Italy.
Cinzia
C
Severini
Department of Medicine of SystemsUniversity of Rome Tor Vergata, Via Montpellier, 100133 Rome, ItalyInstitute of Cell Biology and NeurobiologyCNR, Rome, ItalyDepartment of Integrative Biology and PhysiologyUniversity of Minnesota, Minneapolis, Minnesota, USAIstituto Superiore di SanitàRome, ItalyEBRI FoundationRome, Italy.
Alessandro
A
Bartolomucci
Department of Medicine of SystemsUniversity of Rome Tor Vergata, Via Montpellier, 100133 Rome, ItalyInstitute of Cell Biology and NeurobiologyCNR, Rome, ItalyDepartment of Integrative Biology and PhysiologyUniversity of Minnesota, Minneapolis, Minnesota, USAIstituto Superiore di SanitàRome, ItalyEBRI FoundationRome, Italy Department of Medicine of SystemsUniversity of Rome Tor Vergata, Via Montpellier, 100133 Rome, ItalyInstitute of Cell Biology and NeurobiologyCNR, Rome, ItalyDepartment of Integrative Biology and PhysiologyUniversity of Minnesota, Minneapolis, Minnesota, USAIstituto Superiore di SanitàRome, ItalyEBRI FoundationRome, Italy roberta.possenti@gmail.com.
Roberta
R
Possenti
D000818:Animals; D020013:Calcium Signaling; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004353:Drug Evaluation, Preclinical; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D018149:Glucose Intolerance; D006706:Homeostasis; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D051379:Mice; D009479:Neuropeptides / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D015533:Transcriptional Activation / Q000187:drug effects
D007004:Hypoglycemic Agents; D007328:Insulin; D009479:Neuropeptides; D010455:Peptides; C000593377:TLQP62 peptide; C062040:Vgf protein, rat; D005947:Glucose
GSIS; diabetes; intracellular calcium; neuropeptide; signaling