Mechanism of Action of Novel Glibenclamide Derivatives on Potassium and Calcium Channels for Insulin Secretion.
Glibenclamide is widely used and remains a cornerstone and an effective antihyperglycemic drug. After the casual discovery of its hypoglycemic potential, this compound was introduced for diabetes treatment. However, the long-term side effects reveal that glibenclamide should be replaced by new molecules able to maintain the health of β-cells, protecting them from hyperstimulation/hyperexcitability, hyperinsulinemia, functional failure and cell death. The aim of this review was to highlight the main mechanism of action of glibenclamide and the influence of its derivatives, such as acylhydrazones, sulfonamides and sulfonylthioureas on β-cells potassium and calcium channels for insulin secretion as well as the contribution of these new compounds to restore glucose homeostasis. Furthermore, the role of glibenclamide-based novel structures that promise less excitability of β-cell in a long-term treatment with effectiveness and safety for diabetes therapy was discussed.
Universidade Federal de Santa Catarina, Departamento de Bioquimica, Centro de Ciencias Biologicas, Campus Universitario, Bairro Trindade, Cx. Postal 5069, CEP: 88040-970, Florianopolis, SC, Brazil.
Marisa Jadna Silva
MJS
Frederico
Universidade Federal de Santa Catarina, Departamento de Bioquimica, Centro de Ciencias Biologicas, Campus Universitario, Bairro Trindade, Cx. Postal 5069, CEP: 88040-970, Florianopolis, SC, Brazil.
Allisson Jhonatan Gomes
AJG
Castro
Núcleo de Bioeletricidade Celular (NUBIOCEL) - Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Campus Universitario, Trindade, Cx. Postal 5069, CEP: 88040-970 - Florianopolis, SC, Brazil.
Danusa
D
Menegaz
Universidade Federal de Santa Catarina, Departamento de Bioquimica, Centro de Ciencias Biologicas, Campus Universitario, Bairro Trindade, Cx. Postal 5069, CEP: 88040-970, Florianopolis, SC, Brazil.
Cahue De Bernardis
CB
Murat
Universidade Federal de Santa Catarina, Departamento de Bioquimica, Centro de Ciencias Biologicas, Campus Universitario, Bairro Trindade, Cx. Postal 5069, CEP: 88040-970, Florianopolis, SC, Brazil.
Camila Pires
CP
Mendes
Universidade Federal de Santa Catarina, Departamento de Quimica, Centro de Ciencias Físicas e Matematicas, Campus Universitario, Bairro Trindade, CEP: 88040-900, Florianopolis, SC, Brazil.
Alessandra
A
Mascarello
Universidade Federal de Santa Catarina, Departamento de Quimica, Centro de Ciencias Físicas e Matematicas, Campus Universitario, Bairro Trindade, CEP: 88040-900, Florianopolis, SC, Brazil.
Ricardo Jose
RJ
Nunes
Departamento de Bioquimica, Centro de Ciencias Biologicas, UFSC. Campus Universitario, Bairro Trindade, Cx Postal 5069, CEP: 88040-970 - Florianopolis, Santa Catarina, Brazil.
Fatima Regina Mena Barreto
FRMB
Silva
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D005905:Glyburide / Q000819:agonists / Q000737:chemistry / Q000494:pharmacology*; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects*; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology; D013453:Sulfonylurea Compounds / Q000737:chemistry / Q000494:pharmacology
D015220:Calcium Channels; D007004:Hypoglycemic Agents; D015221:Potassium Channels; D013449:Sulfonamides; D013453:Sulfonylurea Compounds; D005905:Glyburide
Acyl-hydrazones; glibenclamide derivatives; glucose homeostasis; insulin; pancreatic β-cell; sulfonamides; sulfonylthioureas; sulfonylureas