Aldosterone Hypothesis for Cognitive Impairment in Diabetes Mellitus

Horm Metab Res
DOI: 10.1055/s-0043-115226

Increased plasma aldosterone concentration is significantly associated with dementia, which is accentuated by diabetes mellitus (DM). Angiotensin II (AngII) deteriorates cognitive function through neuronal degradation. Lipoproteins, a major source of cholesterol for aldosterone biosynthesis, undergo glycoxidative modifications in the presence of hyperglycemia. We hypothesize that there would be a pathophysiological link between diabetically-modified lipoproteins, angiotensin II, and increased plasma aldosterone concentration for induction of cognitive impairment. Glycoxidized lipoproteins produce significantly more aldosterone from AngII-sensitized adrenocortical cells compared to their native counterparts. The elucidation of signaling mechanisms revealed that modified lipoproteins follow the similar signaling mechanism like AngII for adrenocortical aldosterone release via ERK1/2 and Janus kinase-2 (Jak-2)-mediated pathways. The enhanced aldosterone release from AngII-sensitized adrenocortical cells induced by glycoxidatively modified lipoproteins may play a crucial role in cognitive dysfunction in diabetic individuals along with AngII via a prevailing mode of signaling cascade involving ERK1/2- and Jak-2-dependent pathways.
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