Type 1 Diabetic Heart: Examination of Mitochondrial Structure and MicroRNAs

2015 ◽  
Author(s):  
Dharendra Thapa
Keyword(s):  
Diabetic Heart ◽  
Mitochondrial Structure

scholarly journals CELF1 contributes to aberrant alternative splicing patterns in the type 1 diabetic heart

2018 ◽  
Vol 503 (4) ◽  
pp. 3205-3211 ◽  
Author(s):  
KarryAnne Belanger ◽  
Curtis A. Nutter ◽  
Jin Li ◽  
Sadia Tasnim ◽  
Peiru Liu ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Diabetic Heart ◽  
Splicing Patterns

Abstract 36: Acute Inhibition Of O-GlcNAc Signaling Rescues Inotropic Responsiveness In Type 1 Diabetic Rat Hearts

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Chengxue Qin ◽  
Rochelle S S Sleaby ◽  
Lea M Delbridge ◽  
Amy J Davidoff ◽  
John C Chatham ◽  
...  
Keyword(s):  
Left Ventricular ◽  
Male Rats ◽  
Diabetic Heart ◽  
Diabetic Rat ◽  
Lv Function ◽  
Diabetic Patients ◽  
Cardiac Phenotype ◽  
Rat Hearts ◽  
The Impact

Metabolism of excess glucose is an important component of the aetiology of type 1 diabetes. The cardiac phenotype includes left ventricular (LV) remodelling and LV dysfunction. Increased hexosamine biosythesis (HBP) and downstream upregulation of protein O-GlcNAcylation has been linked to diabetic complications in many organs. Its impact on LV contractile responsiveness is however not well understood. This study aimed to test the hypothesis that acute inhibition of O-GlcNAc signaling protects inotropic responsiveness in type 1 diabetic heart. Hearts isolated from adult Sprague-Dawley male rats were Langendorff-perfused (constant flow, 10ml/min). Baseline and phenylephrine-stimulated (PE, 10μmol/L) LV function was determined in diabetic (8wks post-streptozotocin diabetes, 55mg/kg i.v.) versus non-diabetic sham rats in the presence of pharmacological inhibitors of HBP/O-GlcNAc including 6-diazo-5-oxo-L-norleucine (DON, 20μM) and alloxan (5mM). Diabetic rats exhibited a marked reduction in inotropic responsiveness to PE (Table, mean±SEM, one-way ANOVA, #P<0.05 vs non-diabetic vehicle rats, *P<0.05 vs diabetic vehicle, at 40 mins). Acute interruption of cardiac HBP/O-GlcNAc by DON and Alloxan significantly rescued LV responsiveness to PE in type 1 diabetic rat hearts. These results support further assessment of the impact of upregulated protein O-GlcNAcylation on LV function, particularly in the diabetic heart. Treatment strategies that target HBP may provide significant benefits alone or in combination with current standard treatments, to reduce progression of heart failure and death in type 1 diabetic patients.

scholarly journals Proteomic alterations of distinct mitochondrial subpopulations in the type 1 diabetic heart: contribution of protein import dysfunction

2011 ◽  
Vol 300 (2) ◽  
pp. R186-R200 ◽  
Author(s):  
Walter A. Baseler ◽  
Erinne R. Dabkowski ◽  
Courtney L. Williamson ◽  
Tara L. Croston ◽  
Dharendra Thapa ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Protein Import ◽  
Adenine Nucleotide ◽  
Mitochondrial Protein ◽  
Diabetic Heart ◽  
Acid Oxidation ◽  
Diabetic Patients ◽  
Mitochondrial Protein Import ◽  
Increased Risk

Diabetic cardiomyopathy is associated with increased risk of heart failure in type 1 diabetic patients. Mitochondrial dysfunction is suggested as an underlying contributor to diabetic cardiomyopathy. Cardiac mitochondria are characterized by subcellular spatial locale, including mitochondria located beneath the sarcolemma, subsarcolemmal mitochondria (SSM), and mitochondria situated between the myofibrils, interfibrillar mitochondria (IFM). The goal of this study was to determine whether type 1 diabetic insult in the heart influences proteomic make-up of spatially distinct mitochondrial subpopulations and to evaluate the role of nuclear encoded mitochondrial protein import. Utilizing multiple proteomic approaches (iTRAQ and two-dimensional-differential in-gel electrophoresis), IFM proteomic make-up was impacted by type 1 diabetes mellitus to a greater extent than SSM, as evidenced by decreased abundance of fatty acid oxidation and electron transport chain proteins. Mitochondrial phosphate carrier and adenine nucleotide translocator, as well as inner membrane translocases, were decreased in the diabetic IFM ( P < 0.05 for both). Mitofilin, a protein involved in cristae morphology, was diminished in the diabetic IFM ( P < 0.05). Posttranslational modifications, including oxidations and deamidations, were most prevalent in the diabetic IFM. Mitochondrial heat shock protein 70 (mtHsp70) was significantly decreased in diabetic IFM ( P < 0.05). Mitochondrial protein import was decreased in the diabetic IFM with no change in the diabetic SSM ( P < 0.05). Taken together, these results indicate that mitochondrial proteomic alterations in the type 1 diabetic heart are more pronounced in the IFM. Further, proteomic alterations are associated with nuclear encoded mitochondrial protein import dysfunction and loss of an essential mitochondrial protein import constituent, mtHsp70, implicating this process in the pathogenesis of the diabetic heart.

scholarly journals TLR4 regulates cardiac lipid accumulation and diabetic heart disease in the nonobese diabetic mouse model of type 1 diabetes

2012 ◽  
Vol 303 (6) ◽  
pp. H732-H742 ◽  
Author(s):  
Baojun Dong ◽  
Dake Qi ◽  
Long Yang ◽  
Yan Huang ◽  
Xiaoyan Xiao ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Heart Disease ◽  
Lipid Accumulation ◽  
Nod Mice ◽  
Left Ventricular ◽  
Diabetic Heart ◽  
Early Stages ◽  
Nonobese Diabetic ◽  
Diabetic Heart Disease

Toll-like receptor (TLR)4 regulates inflammation and metabolism and has been linked to the pathogenesis of heart disease. TLR4 is upregulated in diabetic cardiomyocytes, and we examined the role of TLR4 in modulating cardiac fatty acid (FA) metabolism and the pathogenesis of diabetic heart disease in nonobese diabetic (NOD) mice. Both wild-type (WT) NOD and TLR4-deficient NOD animals had increased plasma triglyceride levels after the onset of diabetes. However, by comparison, TLR4-deficient NOD mouse hearts had lower triglyceride accumulation in the early stages of diabetes, which was associated with a reduction in myeloid differentiation primary response gene (88) (MyD88), phosphorylation of p38 MAPK (phospho-p38), lipoprotein lipase (LPL), and JNK levels but increased phospho-AMP-activated protein kinase (AMPK). Oleic acid treatment in H9C2 cardiomyocytes also led to cellular lipid accumulation, which was attenuated by TLR4 small interfering RNA. TLR4 deficiency in the cells decreased FA-induced augmentation of MyD88, phospho-p38, and LPL, suggesting that TLR4 may modulate FA-induced lipid metabolism in cardiomyocytes. In addition, although cardiac function was impaired in both diabetic WT NOD and TLR4-deficient NOD animals compared with control nondiabetic mice, this deficit was less in the diabetic TLR4-deficient NOD mice, which had greater ejection fraction, greater fractional shortening, and increased left ventricular developed pressure in the early stages after the development of diabetes compared with their diabetic WT NOD counterparts. Thus, we conclude that TLR4 plays a role in regulating lipid accumulation in cardiac muscle after the onset of type 1 diabetes, which may contribute to cardiac dysfunction.

scholarly journals P30 Effects of carnitine supplementation in the type 1 diabetic heart: an in vivo hyperpolarized mrs study

2018 ◽  
Author(s):  
Dragana Savic ◽  
Kerstin Timm ◽  
Vicky Ball ◽  
Lisa Heather ◽  
Damian Tyler
Keyword(s):  
Diabetic Heart ◽  
Carnitine Supplementation

scholarly journals Exercise-induced cardiac performance in autoimmune (Type 1) diabetes is associated with a decrease in myocardial diacylglycerol

2012 ◽  
Vol 113 (5) ◽  
pp. 817-826 ◽  
Author(s):  
Rajprasad Loganathan ◽  
Lesya Novikova ◽  
Igor G. Boulatnikov ◽  
Irina V. Smirnova
Keyword(s):  
Type 1 Diabetes ◽  
Exercise Training ◽  
Mitochondrial Fraction ◽  
Left Ventricular ◽  
Cardiac Performance ◽  
Diabetic Heart ◽  
Hemodynamic Assessment ◽  
Pkc Signaling ◽  
Exercise Induced

One of the fundamental biochemical defects underlying the complications of diabetic cardiovascular system is elevation of diacylglycerol (DAG) and its effects on protein kinase C (PKC) signaling. It has been noted that exercise training attenuates poor cardiac performance in Type 1 diabetes. However, the role of PKC signaling in exercise-induced alleviation of cardiac abnormalities in diabetes is not clear. We investigated the possibility that exercise training modulates PKC-βII signaling to elicit its beneficial effects on the diabetic heart. bio-breeding diabetic resistant rats, a model reminiscent of Type 1 diabetes in humans, were randomly assigned to four groups: 1) nonexercised nondiabetic (NN); 2) nonexercised diabetic (ND); 3) exercised nondiabetic; and 4) exercised diabetic. Treadmill training was initiated upon the onset of diabetes. At the end of 8 wk, left ventricular (LV) hemodynamic assessment revealed compromised function in ND compared with the NN group. LV myocardial histology revealed increased collagen deposition in ND compared with the NN group, while electron microscopy showed a reduction in the viable mitochondrial fraction. Although the PKC-βII levels and activity were unchanged in the diabetic heart, the DAG levels were increased. With exercise training, the deterioration of LV structure and function in diabetes was attenuated. Notably, improved cardiac performance in training was associated with a decrease in myocardial DAG levels in diabetes. Exercise-induced benefits on cardiac performance in diabetes may be mediated by prevention of an increase in myocardial DAG levels.

scholarly journals Impact of mitochondria phospholipid hydroperoxide glutathione peroxidase (mPHGPx) overexpression on the type 1 diabetic heart

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Sara E Lewis ◽  
Erinne R Dabkowski ◽  
Walter A Baseler ◽  
Danielle L Shepherd ◽  
Tara L Croston ◽  
...  
Keyword(s):  
Glutathione Peroxidase ◽  
Diabetic Heart ◽  
Phospholipid Hydroperoxide Glutathione Peroxidase ◽  
Phospholipid Hydroperoxide

Sex-dependent impairment of cardiac action potential conduction in type 1 diabetic rats

2009 ◽  
Vol 296 (5) ◽  
pp. H1442-H1450 ◽  
Author(s):  
Yakhin Shimoni ◽  
Teresa Emmett ◽  
Robyn Schmidt ◽  
Anders Nygren ◽  
Gary Kargacin
Keyword(s):  
Gap Junction ◽  
Enzyme Inhibitor ◽  
Female Rats ◽  
Diabetic Heart ◽  
Impulse Propagation ◽  
Male And Female Rats ◽  
Ventricular Cells ◽  
Junction Protein ◽  
Gap Junction Protein

The incidence of diabetes mellitus is increasing. Cardiac dysfunction often develops, resulting in diverse arrhythmias. These arise from ion channel remodeling or from altered speed and pattern of impulse propagation. Few studies have investigated impulse propagation in the diabetic heart. We previously showed a reduced conduction reserve in the diabetic heart, with associated changes in intercellular gap junctions. The present study investigated whether these effects are sex specific. Hearts from control and streptozotocin-diabetic male and female rats were used. Optical mapping was performed with the voltage-sensitive dye di-4-ANEPPS, using Langendorff-perfused hearts. Isolated ventricular cells and tissue sections were used for immunofluorescent labeling of the gap junction protein connexin43 (Cx43). The gap junction uncoupler heptanol (0.75 mM) or elevated K+ (9 mM, to reduce cell excitability) produced significantly greater slowing of propagation in diabetic males than females. In ovariectomized diabetic females, 9 mM K+ slowed conduction significantly more than in nonovariectomized females. The subcellular redistribution (lateralization) of the gap junction protein Cx43 was smaller in diabetic females. Pretreatment of diabetic males with the angiotensin-converting enzyme inhibitor quinapril reduced Cx43 lateralization and the effects of 9 mM K+ on propagation. In conclusion, the slowing of cardiac impulse propagation in type 1 diabetes is smaller in female rats, partly due to the presence of female sex hormones. This difference is (partly) mediated by sex differences in activation of the cardiac renin-angiotensin system.

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