Insulin signaling alters antioxidant capacity in the diabetic heart

AbstractThe cAMP-dependent protein kinase (PKA) signaling pathway is the primary means by which the heart regulates moment-to-moment changes in contractility and metabolism. We have previously found that PKA signaling is dysfunctional in the diabetic heart, yet the underlying mechanisms are not fully understood. The objective of this study was to determine if decreased insulin signaling contributes to a dysfunctional PKA response. To do so, we isolated adult cardiomyocytes (ACMs) from wild type and Akita type 1 diabetic mice. ACMs were cultured in the presence or absence of insulin and PKA signaling was visualized by immunofluorescence microscopy using an antibody that recognizes proteins specifically phosphorylated by PKA. We found significant decreases in proteins phosphorylated by PKA in wild type ACMs cultured in the absence of insulin. Akita ACMs also had decreased PKA signaling in the absence of insulin and this was not rescued by insulin. The decrease in PKA signaling was observed regardless of whether the kinase was stimulated with a beta-agonist, a cell-permeable cAMP analog, or with phosphodiesterase inhibitors. PKA content was unaffected, suggesting that the decrease in PKA signaling may be occurring by the loss of specific PKA substrates. Phospho-specific antibodies were therefore used to discern which potential substrates may be sensitive to the loss of insulin. Contractile proteins were phosphorylated similarly in wild type and Akita ACMs regardless of insulin. However, phosphorylation of the glycolytic regulator, PFK-2, was significantly decreased in an insulin-dependent manner in wild type ACMs and in an insulin-independent manner in Akita ACMs. These results demonstrate a defect in PKA activation in the diabetic heart, mediated in part by deficient insulin signaling, that results in an abnormal activation of a primary metabolic regulator.

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Undertreatment of diabetic heart failure patients is prevented by referral to specialized heart failure clinics. An analysis from the Danish Heart Failure Clinics Network

European Journal of Heart Failure Supplements ◽

10.1016/s1567-4215(08)60023-5 ◽

2008 ◽

Vol 7 ◽

pp. 9-9

Author(s):

I GUSTAFSSON ◽

L MADSEN ◽

F GUSTAFSSON ◽

M SCHOU ◽

L VIDEBAEK ◽

...

Keyword(s):

Heart Failure ◽

Diabetic Heart ◽

Heart Failure Patients

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Trans-resveratrol supplement lowers lipid peroxidation responses of exercise in male Wistar rats

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000654 ◽

2020 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Masoud Nasiri ◽

Saja Ahmadizad ◽

Mehdi Hedayati ◽

Tayebe Zarekar ◽

Mehdi Seydyousefi ◽

...

Keyword(s):

Lipid Peroxidation ◽

Antioxidant Capacity ◽

Total Antioxidant Capacity ◽

Wistar Rats ◽

Enzymatic Antioxidants ◽

Acute Response ◽

Total Antioxidant ◽

Male Wistar Rats ◽

Exercise Induced ◽

And Control

Abstract. Physical exercise increases free radicals production; antioxidant supplementation may improve the muscle fiber’s ability to scavenge ROS and protect muscles against exercise-induced oxidative damage. This study was designed to examine the effects of all-trans resveratrol supplementation as an antioxidant to mediate anti-oxidation and lipid per-oxidation responses to exercise in male Wistar rats. Sixty-four male Wistar rats were randomly divided into four equal number (n = 16) including training + supplement (TS), training (T), supplement (S) and control (C) group. The rats in TS and S groups received a dose of 10 mg/kg resveratrol per day via gavage. The training groups ran on a rodent treadmill 5 times per week at the speed of 10 m/min for 10 min; the speed gradually increased to 30 m/min for 60 minutes at the end of 12th week. The acute phase of exercise protocol included a speed of 25 m/min set to an inclination of 10° to the exhaustion point. Superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) activity, non-enzymatic antioxidants bilirubin, uric acid, lipid peroxidation levels (MDA) and the total antioxidant capacity (TAC) were measured after the exercise termination. The data were analyzed by using one-way ANOVA. The result showed that endurance training caused a significant increase in MDA level [4.5 ± 0.75 (C group) vs. 5.9 ± 0.41 nmol/l (T group)] whereas it decreased the total antioxidant capacity [8.5 ± 1.35 (C group) vs. 7.1 ± 0.55 mmol/l (T group)] (p = 0.001). In addition, GPx and CAT decreased but not significantly (p > 0.05). The training and t-resveratrol supplementation had no significant effect on the acute response of all variables except MDA [4.3 ± 1.4 (C group) vs. 4.0 ± 0.90 nmol/l (TS group)] (p = 0.001) and TAC [8.5 ± 0.90 (C group) vs. 6.6 ± 0.80 mmol/l (TS group)] (p = 0.004). It was concluded that resveratrol supplementation may prevent exercise-induced oxidative stress by preventing lipid peroxidation.

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Folate and vitamin B-12 deficiencies additively impaired memory function and disturbed the gut microbiota in amyloid-β infused rats

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000624 ◽

2019 ◽

pp. 1-13 ◽

Cited By ~ 2

Author(s):

Sunmin Park ◽

Sunna Kang ◽

Da Sol Kim

Keyword(s):

Insulin Resistance ◽

Gut Microbiota ◽

Insulin Signaling ◽

Gut Microbiome ◽

Metabolic Diseases ◽

Memory Function ◽

Amyloid Β ◽

Impaired Memory ◽

Ca1 Region ◽

Folate And Vitamin B12

Abstract. Folate and vitamin B12(V-B12) deficiencies are associated with metabolic diseases that may impair memory function. We hypothesized that folate and V-B12 may differently alter mild cognitive impairment, glucose metabolism, and inflammation by modulating the gut microbiome in rats with Alzheimer’s disease (AD)-like dementia. The hypothesis was examined in hippocampal amyloid-β infused rats, and its mechanism was explored. Rats that received an amyloid-β(25–35) infusion into the CA1 region of the hippocampus were fed either control(2.5 mg folate plus 25 μg V-B12/kg diet; AD-CON, n = 10), no folate(0 folate plus 25 μg V-B12/kg diet; AD-FA, n = 10), no V-B12(2.5 mg folate plus 0 μg V-B12/kg diet; AD-V-B12, n = 10), or no folate plus no V-B12(0 mg folate plus 0 μg V-B12/kg diet; AD-FAB12, n = 10) in high-fat diets for 8 weeks. AD-FA and AD-VB12 exacerbated bone mineral loss in the lumbar spine and femur whereas AD-FA lowered lean body mass in the hip compared to AD-CON(P < 0.05). Only AD-FAB12 exacerbated memory impairment by 1.3 and 1.4 folds, respectively, as measured by passive avoidance and water maze tests, compared to AD-CON(P < 0.01). Hippocampal insulin signaling and neuroinflammation were attenuated in AD-CON compared to Non-AD-CON. AD-FAB12 impaired the signaling (pAkt→pGSK-3β) and serum TNF-α and IL-1β levels the most among all groups. AD-CON decreased glucose tolerance by increasing insulin resistance compared to Non-AD-CON. AD-VB12 and AD-FAB12 increased insulin resistance by 1.2 and 1.3 folds, respectively, compared to the AD-CON. AD-CON and Non-AD-CON had a separate communities of gut microbiota. The relative counts of Bacteroidia were lower and those of Clostridia were higher in AD-CON than Non-AD-CON. AD-FA, but not V-B12, separated the gut microbiome community compared to AD-CON and AD-VB12(P = 0.009). In conclusion, folate and B-12 deficiencies impaired memory function by impairing hippocampal insulin signaling and gut microbiota in AD rats.

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The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000116 ◽

2012 ◽

Vol 82 (3) ◽

pp. 228-232 ◽

Cited By ~ 7

Author(s):

Mauro Serafini ◽

Giuseppa Morabito

Keyword(s):

Antioxidant Capacity ◽

Dietary Intervention ◽

Ex Vivo ◽

The Body ◽

Dietary Polyphenols ◽

Enzymatic Antioxidant ◽

Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

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