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The renin-angiotensin system in the pathophysiology of type 2 diabetes
1Department of Human Biology, NUTRIM School for Nutrition, Toxicology & Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands. G.Goossens@maastrichtuniversity.nl
Abstract:
Increased activation of the renin-angiotensin system (RAS) has been related to cardiovascular disease and type 2 diabetes mellitus. Most randomized clinical trials have demonstrated that RAS blockade reduces the incidence of type 2 diabetes, which has been explained by improved insulin secretion and insulin sensitivity. In this review, an overview of the mechanisms that may underlie the association between the RAS and type 2 diabetes will be provided, with focus on skeletal muscle and adipose tissue function. This will include discussion of several human studies performed in our laboratory to investigate the metabolic and hemodynamic effects of the RAS, combining in vivo measurements of whole-body and tissue metabolism with molecular and immunohistochemical approaches. Available data suggest that the detrimental effects of the RAS on insulin secretion are mediated by a reduction in pancreatic blood flow and induction of islet fibrosis, oxidative stress as well as inflammation, whereas both impaired skeletal muscle function and adipose tissue dysfunction may underlie RAS-induced insulin resistance. Thus, although future studies in humans are warranted, current evidence supports that targeting the RAS in intervention studies may improve metabolic and cardiovascular function in conditions of insulin resistance like obesity and type 2 diabetes.
Insights
Targeting the renin-angiotensin system (RAS) may improve metabolic and cardiovascular health. RAS blockade benefits type 2 diabetes by enhancing insulin secretion and sensitivity, particularly in skeletal muscle and adipose tissue.
Area of Science:
- Endocrinology
- Cardiovascular Science
- Metabolic Research
Background:
- The renin-angiotensin system (RAS) is implicated in cardiovascular disease and type 2 diabetes.
- RAS blockade has shown promise in reducing type 2 diabetes incidence.
- Improved insulin secretion and sensitivity are potential mechanisms for RAS blockade benefits.
Purpose of the Study:
- To review mechanisms linking the RAS and type 2 diabetes.
- To focus on the role of skeletal muscle and adipose tissue in RAS-induced metabolic dysfunction.
- To present findings from human studies investigating RAS effects on metabolism and hemodynamics.
Main Methods:
- Review of existing literature and human studies.
- In vivo measurements of whole-body and tissue metabolism.
- Molecular and immunohistochemical analyses of tissue function.
Main Results:
- RAS activation negatively impacts insulin secretion via reduced pancreatic blood flow, islet fibrosis, oxidative stress, and inflammation.
- Impaired skeletal muscle and adipose tissue function contribute to RAS-induced insulin resistance.
- Human studies explored metabolic and hemodynamic effects of RAS.
Conclusions:
- The RAS plays a significant role in the pathophysiology of type 2 diabetes.
- Targeting the RAS may offer therapeutic benefits for metabolic and cardiovascular conditions like obesity and type 2 diabetes.
- Further human studies are needed to confirm these findings.
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