Angiotensin II (AII), the active component of the renin angiotensin system (RAS), plays a vital role in the regulation of physiological processes of the cardiovascular system, but also has autocrine and paracrine actions in various tissues and organs. Many studies have shown the existence of RAS in the pancreas of humans and rodents. The aim of this study was to evaluate potential signaling pathways mediated by AII in isolated pancreatic islets of rats. Phosphorylation of MAPKs (ERK1/2, JNK and p38MAPK), and the interaction between proteins JAK/STAT were evaluated. AII increased JAK2/STAT1 (42%) and JAK2/STAT3 (100%) interaction without altering the total content of JAK2. Analyzing the activation of MAPKs (ERK1/2, JNK and p38MAPK) in isolated pancreatic islets from rats we observed that AII rapidly (3 min) promoted a significant increase in the phosphorylation degree of these proteins after incubation with the hormone. Curiously JNK protein phosphorylation was inhibited by DPI, suggesting the involvement of NAD(P)H oxidase in the activation of protein.

ObjectiveThe aim of this project was to evaluate the RAS inhibition on protein expression and activation of components of NAD(P)H oxidase enzyme in pancreatic islets of experimental model of insulin resistance.Methods and ResultsInsulin resistance was induced by neonatal treatment with monosodium glutamate (MSG). MSG and controls (CTL) received losartan (30mg/Kg/dia) or equal volume of vehicle by gavage for 8 days. The protein expression of p47PHOX subunit was assessed by Western Blot. Pancreatic islets of MSG animals showed an increase of 15% in protein expression of p47PHOX compared with the CTL group. However, treatment with losartan in the MSG group led to 30% of decrease in expression of this protein. Liver of animals MSG, showed a significant increase (p<0.01) of the p47PHOX content compared to CTL which was reversed after losartan reaching to CTL levels. Increased superoxide generation in pancreatic islets of MSG animals was blunted after losartan treatment.ConclusionWe conclude that losartan treatment reduces the expression of subunit p47 PHOX in both hepatic tissue and islets of MSG rats which may act as an important modulator of insulin resistance of this animals.

Obesity is characterized by the activation of an inflammatory process in metabolically active sites such as adipose tissue and liver. The consequence of this response is an increase proinflammatory markers. This activation response in obesity is mediated by some specific signaling pathways including kinase families such as JNK, MAPK and IKKb. It is known that these molecules can lead to impairment of insulin signaling and result in the development of insulin resistance. The aim of this study was to evaluate the expression of these molecules in different models of obesity. Liver, muscle and adipose tissue from MSG‐obese rats (normophagic) and High‐fat induced obesity‐HF (hyperphagic) were evaluated. MSG‐obese rats showed significant increase in phosphorylation of ERK1/2 in liver and adipose tissue while HF‐rats showed a decreased in phosphorylation of this kinase in adipose tissue. Preliminary data also showed a differential modulation of p38MAPK, JNK and IKKb of these models. It is possible that the different energy load condition may have an important role in the signaling pathways of these molecules associated with the development of obesity‐induced inflammation.

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