Treatments for diabetes mellitus type II: New perspectives regarding the possible role of calcium and cAMP interaction

Treatments for diabetes mellitus type II: New perspectives regarding the possible role of calcium and cAMP interaction

Author Carvalho, Diego Soares Autor UNIFESP Google Scholar
Almeida, Alexandre Aparecido de Autor UNIFESP Google Scholar
Borges, Aurelio Ferreira Google Scholar
Campos, Vannucci Autor UNIFESP Google Scholar
Abstract Diabetes mellitus (DM) is among the top ten causes of death worldwide. It is considered to be one of the major global epidemics of the 21st century, with a significant impact on public health budgets. DM is a metabolic disorder with multiple etiologies. Its pathophysiology is marked by dysfunction of pancreatic beta-cells which compromises the synthesis and secretion of insulin along with resistance to insulin action in peripheral tissues (muscle and adipose). Subjects presenting insulin resistance in DM type 2 often also exhibit increased insulin secretion and hyperinsulinemia. Insulin secretion is controlled by several factors such as nutrients, hormones, and neural factors. Exocytosis of insulin granules has, as its main stimulus, increased intracellular calcium ([Ca+2] i) and it is further amplified by cyclic AMP (cAMP). In the event of this hyperfunction, it is very common for beta-cells to go into exhaustion leading to failure or death. Several animal studies have demonstrated pleiotropic effects of L-type Ca2+ channel blockers (CCBs). In animal models of obesity and diabetes, treatment with CCBs promoted restoration of insulin secretion, glycemic control, and reduction of pancreatic beta-cell apoptosis. In addition, hypertensive individuals treated with CCBs presented a lower incidence of DM when compared with other antihypertensive agents. In this review, we propose that pharmacological manipulation of the Ca2+/cAMP interaction system could lead to important targets for pharmacological improvement of insulin secretion in DM type 2.
Keywords Insulin secretion
Ca2+/cAMP signaling interaction
Diabetes
Language English
Date 2018
Published in European Journal Of Pharmacology. Amsterdam, v. 830, p. 9-16, 2018.
ISSN 0014-2999 (Sherpa/Romeo, impact factor)
Publisher Elsevier Science Bv
Extent 9-16
Origin http://dx.doi.org/10.1016/j.ejphar.2018.04.002
Access rights Closed access
Type Revisão
Web of Science ID WOS:000432890900002
URI http://repositorio.unifesp.br/handle/11600/45962

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