Abstract
Results Prolonged exposure to palmitate increased the expression of ACE and AngII type 1 receptor (ATR1) and decreased the ACE2 expression, which was partly offset by berberine. In ob/ob mice, berberine increased in tolerance to glucose, improved abnormal β-cell and α-cell distributions, upregulated ACE2 expression, and decreased autophagosomes and the expression of LC3 and SQSTM1/p62. Autophagosomes and expression of LC3 and SQSTM1/p62 were increased in ACE2KO mice. Conclusions We demonstrated that berberine may improve the pancreatic islet function by regulating local RAS-mediated autophagy under metabolic stress.
Highlights
Obesity, which is due to a chronic imbalance between energy “input” and “output”, has become a major public health problem because of its epidemic proportions worldwide [1]
With the administration of palmitate at 0.2 or 0.4 mmol/L, the angiotensin-converting enzyme 2 (ACE2) mRNA expression was markedly decreased by 23% or 41%, respectively (p < 0:05) (Figure 1(c))
Similar to the mRNA expression, the angiotensinconverting enzyme (ACE) expression was significantly upregulated, whereas the ACE2 expression was clearly decreased (Figure 1(f)). These results indicate that palmitate activates the ACE/ATR1 axis and inhibits the ACE2/Mas receptor (Mas) axis dependent on palmitate concentration in isolated islets
Summary
Obesity, which is due to a chronic imbalance between energy “input” and “output”, has become a major public health problem because of its epidemic proportions worldwide [1]. Extensive research has proven that the renin-angiotensin system (RAS) is strongly associated with the energy imbalance and organ dysfunction caused by obesity [2, 3]. The angiotensinconverting enzyme (ACE)/Ang II (angiotensin II)/AngII type 1 receptor (ATR1) axis is responsible for the potent vasoconstriction, proinflammatory, prooxidative, proliferative, and hypertrophic effects. The ACE2/Ang-(1–7)/Mas receptor (Mas) axis constitutes an alternative axis that represents an intrinsic mechanism for inducing inverse actions by regulating the ACE/Ang II/ATR1 axis, inducing many beneficial effects in energy balance and beta-cell protection [4].
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