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Horm Metab Res 2017; 49(09): 716-718
DOI: 10.1055/s-0043-115226
Hypothesis
© Georg Thieme Verlag KG Stuttgart · New York

Aldosterone Hypothesis for Cognitive Impairment in Diabetes Mellitus

Sarama Saha
1   Department of Internal Medicine III, Carl Gustav Carus Medical School, Technical University of Dresden, Dresden, Germany
2   Department of Biochemistry, AIIMS, Rishikesh, India
,
Stefan R. Bornstein
1   Department of Internal Medicine III, Carl Gustav Carus Medical School, Technical University of Dresden, Dresden, Germany
,
Juergen Graessler
1   Department of Internal Medicine III, Carl Gustav Carus Medical School, Technical University of Dresden, Dresden, Germany
,
Sasanka Chakrabarti
3   Department of Biochemistry, IIMSAR, Haldia, India
,
Steffi Kopprasch
1   Department of Internal Medicine III, Carl Gustav Carus Medical School, Technical University of Dresden, Dresden, Germany
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Publikationsverlauf

received 09. Juni 2017

accepted 20. Juni 2017

Publikationsdatum:
23. August 2017 (online)

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Abstract

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.

Key words

glycoxidative modification - dementia - angiotensin II - aldosterone - lipoproteins
 

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