scholarly journals AKAP150 Contributes to Enhanced Vascular Tone by Facilitating Large-Conductance Ca 2+ -Activated K + Channel Remodeling in Hyperglycemia and Diabetes Mellitus

2014 ◽  
Vol 114 (4) ◽  
pp. 607-615 ◽  
Author(s):  
Matthew A. Nystoriak ◽  
Madeline Nieves-Cintrón ◽  
Patrick J. Nygren ◽  
Simon A. Hinke ◽  
C. Blake Nichols ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
High Fat Diet ◽  
Vascular Tone ◽  
Scaffolding Protein ◽  
K Channel ◽  
High Fat ◽  
Activated T Cells ◽  
Genetic Ablation ◽  
Channel Function ◽  
Arterial Blood

Rationale : Increased contractility of arterial myocytes and enhanced vascular tone during hyperglycemia and diabetes mellitus may arise from impaired large-conductance Ca 2+ -activated K + (BK Ca ) channel function. The scaffolding protein A-kinase anchoring protein 150 (AKAP150) is a key regulator of calcineurin (CaN), a phosphatase known to modulate the expression of the regulatory BK Ca β1 subunit. Whether AKAP150 mediates BK Ca channel suppression during hyperglycemia and diabetes mellitus is unknown. Objective : To test the hypothesis that AKAP150-dependent CaN signaling mediates BK Ca β1 downregulation and impaired vascular BK Ca channel function during hyperglycemia and diabetes mellitus. Methods and Results : We found that AKAP150 is an important determinant of BK Ca channel remodeling, CaN/nuclear factor of activated T-cells c3 (NFATc3) activation, and resistance artery constriction in hyperglycemic animals on high-fat diet. Genetic ablation of AKAP150 protected against these alterations, including augmented vasoconstriction. d -glucose–dependent suppression of BK Ca channel β1 subunits required Ca 2+ influx via voltage-gated L-type Ca 2+ channels and mobilization of a CaN/NFATc3 signaling pathway. Remarkably, high-fat diet mice expressing a mutant AKAP150 unable to anchor CaN resisted activation of NFATc3 and downregulation of BK Ca β1 subunits and attenuated high-fat diet–induced elevation in arterial blood pressure. Conclusions : Our results support a model whereby subcellular anchoring of CaN by AKAP150 is a key molecular determinant of vascular BK Ca channel remodeling, which contributes to vasoconstriction during diabetes mellitus.

scholarly journals Berberine elevates cardiolipin in heart of offspring from mouse dams with high fat diet-induced gestational diabetes mellitus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Laura K. Cole ◽  
Genevieve C. Sparagna ◽  
Marilyne Vandel ◽  
Bo Xiang ◽  
Vernon W. Dolinsky ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Mitochondrial Function ◽  
High Fat Diet ◽  
Fatty Acid Uptake ◽  
Isoquinoline Alkaloid ◽  
Acid Uptake ◽  
High Fat ◽  
Low Fat

AbstractBerberine (BBR) is an isoquinoline alkaloid from plants known to improve cardiac mitochondrial function in gestational diabetes mellitus (GDM) offspring but the mechanism is poorly understood. We examined the role of the mitochondrial phospholipid cardiolipin (CL) in mediating this cardiac improvement. C57BL/6 female mice were fed either a Lean-inducing low-fat diet or a GDM-inducing high-fat diet for 6 weeks prior to breeding. Lean and GDM-exposed male offspring were randomly assigned a low-fat, high-fat, or high-fat diet containing BBR at weaning for 12 weeks. The content of CL was elevated in the heart of GDM offspring fed a high fat diet containing BBR. The increase in total cardiac CL was due to significant increases in the most abundant and functionally important CL species, tetralinoleoyl-CL and this correlated with an increase in the expression of the CL remodeling enzyme tafazzin. Additionally, BBR treatment increased expression of cardiac enzymes involved in fatty acid uptake and oxidation and electron transport chain subunits in high fat diet fed GDM offspring. Thus, dietary BBR protection from cardiac dysfunction in GDM exposed offspring involves improvement in mitochondrial function mediated through increased synthesis of CL.

Hypoglycemic effects of Auricularia auricula polysaccharides on high fat diet and streptozotocin-induced diabetic mice using metabolomics analysis

2021 ◽  
Author(s):  
nannan liu ◽  
Xuefeng Chen ◽  
Juanna Song ◽  
Mengyin Chen ◽  
Pin Gong ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
High Fat Diet ◽  
Diabetic Mice ◽  
Male Mice ◽  
High Fat ◽  
Auricularia Auricula ◽  
Ultrahigh Performance Liquid Chromatography ◽  
Metabolomic Approach ◽  
Metabolomics Analysis

This study evaluated the hypoglycemic effect of Auricularia auricula polysaccharides (AAPs) on streptozotocin-induced type 2 diabetes mellitus (T2DM) male mice (C57BL/6J) using a metabolomic approach based on ultrahigh-performance liquid chromatography–Q...

scholarly journals Gravin Scaffolding Protein Mediates Signaling in High Fat Diet Model

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Qiying Fan ◽  
Andrea C Diaz Diaz ◽  
Cori S Wijaya ◽  
Xing Yin ◽  
Sonal Singh ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Scaffolding Protein ◽  
High Fat ◽  
Diet Model

scholarly journals A Low-Carbohydrate/High-Fat Diet Improves Glucoregulation in Type 2 Diabetes Mellitus by Reducing Postabsorptive Glycogenolysis

2004 ◽  
Vol 89 (12) ◽  
pp. 6193-6197 ◽  
Author(s):  
Gideon Allick ◽  
Peter H. Bisschop ◽  
Mariette T. Ackermans ◽  
Erik Endert ◽  
Alfred J. Meijer ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
High Fat Diet ◽  
High Fat ◽  
Low Carbohydrate
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