Treatments for diabetes mellitus type II: New perspectives regarding the possible role of calcium and cAMP interaction
Data
2018
Autores
Carvalho, Diego Soares 
Almeida, Alexandre Aparecido de
Campos, Vannucci
Tipo
Revisão
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Resumo
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.
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Citação
European Journal Of Pharmacology. Amsterdam, v. 830, p. 9-16, 2018.