Key result
A high-fat high-carbohydrate diet for 32 weeks induced prediabetes and significantly elevated local renin-angiotensin-aldosterone system components and oxidative stress markers in selected organs.
Why the study?
The detrimental ramifications of moderate hyperglycemia in prediabetes, the affected organ systems, and the underlying mechanistic pathways are not elucidated.
Does a high-fat high-carbohydrate diet induce prediabetes and alter local RAAS activity in selected organs in male Sprague-Dawley rats?
Does a high-fat high-carbohydrate diet induce prediabetes and alter local RAAS activity in selected organs in male Sprague-Dawley rats?
p-value: p=<0.05
Diet-induced prediabetes in rats upregulates local RAAS components and oxidative stress markers in multiple organs, suggesting a mechanism for the early derangements that lead to type 2 diabetes complications.
Diet-induced prediabetes upregulates local RAAS and oxidative stress in rat organs; hypothesis-generating for human T2D mechanisms and requires clinical validation.
AIMS/INTRODUCTION: Derangements often observed with type 2 diabetes are associated with disturbances in renin-angiotensin-aldosterone system (RAAS) activity. A positive correlation between local RAAS activity and the complications observed in type 2 diabetes has been noted. However, the detrimental ramifications due to moderate hyperglycemia noted in prediabetes, and the affected organ system and mechanistic pathways are not elucidated. Hence, this study investigated the effects of diet-induced prediabetes on RAAS in various organs. MATERIALS AND METHODS: Male Sprague-Dawley rats were separated into two groups: (i) non-prediabetes through exposure to standard rat chow group; and (ii) diet-induced prediabetes group by exposure to a high-fat high-carbohydrate diet for 32 weeks. RAAS activity in the skeletal muscle, adipose tissue, liver, pancreas and heart was determined through the analysis of RAAS components, such as renin, angiotensinogen, angiotensin-converting enzyme and angiotensin II type 1 receptor through polymerase chain reaction, as well as the quantification of angiotensin II and aldosterone concentration. Furthermore, nicotinamide adenine dinucleotide phosphate oxidase, superoxide dismutase and glutathione peroxidase 1 concentrations were determined in the skeletal muscle, pancreas and heart, in addition to the hepatic triglycerides. RESULTS: The RAAS components were elevated in the diet-induced prediabetes group when compared with the non-prediabetes group. This was further accompanied by increased nicotinamide adenine dinucleotide phosphate oxidase and reduced superoxide dismutase and glutathione peroxidase 1 concentrations in the selected organs, in addition to the elevated hepatic triglycerides concentration in the diet-induced prediabetes by comparison to non-prediabetes group. CONCLUSIONS: Due to these observed changes, we suggest that local RAAS activity in the prediabetes state in selected organs elicits the derangements noted in type 2 diabetes.
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Mkhize et al. (2021) studied Diet-induced prediabetes (n=12). High-fat high-carbohydrate diet with 15% fructose drinking water vs. Standard rat chow with normal drinking water was evaluated on Relative expression of RAAS components (renin, AGT, ACE, AT1R) and protein concentration of Ang II and aldosterone in selected organs (p=<0.05). A high-fat high-carbohydrate diet for 32 weeks induced prediabetes and significantly elevated local renin-angiotensin-aldosterone system components and oxidative stress markers in selected organs.
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