Research on the renin-angiotensin system (RAS) has contributed significantly to advances in understanding cardiovascular and renal homeostasis and to the treatment of cardiovascular diseases. This review offers a brief history of the RAS with an overview of its major components and their functions, as well as blockers of the RAS, their clinical usage and current research that targets various components of the RAS. Because angiotensin-converting enzyme (ACE) metabolizes two biologically active peptides, one in the kallikrein-kinin system (KKS) and one in the RAS, it is the essential connection between the two systems. ACE releases very powerful hypertensive agent, angiotensin II and also inactivates strong hypotensive peptide, bradykinin. Inhibition of ACE thus has a dual effect, resulting in decreased angiotensin II and increased bradykinin. We described the KKS as well.

Bordetella pertussis toxin (PTx), also known as islet-activating protein, induces insulin secretion by ADP-ribosylation of inhibitory G proteins. PTx-induced insulin secretion may result either from inactivation of Gα(o) proteins or from combined inactivation of Gα(o), Gα(i1), Gα(i2), and Gα(i3) isoforms. However, the specific role of Gα(i2) in pancreatic β-cells still remains unknown. In global (Gα(i2)(-/-)) and β-cell-specific (Gα(i2)(βcko)) gene-targeted Gα(i2) mouse models, we studied glucose homeostasis and islet functions. Insulin secretion experiments and intracellular Ca²⁺ measurements were used to characterize Gα(i2) function in vitro. Gα(i2)(-/-) and Gα(i2)(βcko) mice showed an unexpected metabolic phenotype, i.e., significantly lower plasma insulin levels upon intraperitoneal glucose challenge in Gα(i2)(-/-) and Gα(i2)(βcko) mice, whereas plasma glucose concentrations were unchanged in Gα(i2)(-/-) but significantly increased in Gα(i2)(βcko) mice. These findings indicate a novel albeit unexpected role for Gα(i2) in the expression, turnover, and/or release of insulin from islets. Detection of insulin secretion in isolated islets did not show differences in response to high (16 mM) glucose concentrations between control and β-cell-specific Gα(i2)-deficient mice. In contrast, the two- to threefold increase in insulin secretion evoked by L-arginine or L-ornithine (in the presence of 16 mM glucose) was significantly reduced in islets lacking Gα(i2). In accord with a reduced level of insulin secretion, intracellular calcium concentrations induced by the agonistic amino acid L-arginine did not reach control levels in β-cells. The presented analysis of gene-targeted mice provides novel insights in the role of β-cell Gα(i2) showing that amino acid-induced insulin-release depends on Gα(i2).

Electricity grids are in a transition phase. With the rise of renewable energy, energy "prosumers," and electric vehicles, traditional models of matching supply and demand are no longer adequate. Grid pilot projects can help identify ways to improve cybersecurity in future grids.