ArticleCirculation research2009
Role of SREBP-1 in the development of parasympathetic dysfunction in the hearts of type 1 diabetic Akita mice.
Article in Circulation research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22 citing papers in PubMed, 32 citations in OpenAlex.
- SREBP1 Transactivation of NHE3 Impairs Cardiac Contraction and Aggravates Heart Failure.Circulation · 2026Article
- AAV9-mediated gene supplementation therapy prevents and rescues arrhythmogenic cardiomyopathy in Pnpla2-mutated mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Metabolic remodelling in atrial fibrillation: manifestations, mechanisms and clinical implications.Nature reviews. Cardiology · 2024Review
- Fluoxetine Treatment Decreases Cardiac Vagal Input and Alters the Serotonergic Modulation of the Parasympathetic Outflow in Diabetic Rats.International journal of molecular sciences · 2022Article
- Structural and Electrical Remodeling of the Sinoatrial Node in Diabetes: New Dimensions and Perspectives.Frontiers in endocrinology · 2022Review
- Impaired regulation of heart rate and sinoatrial node function by the parasympathetic nervous system in type 2 diabetic mice.Scientific reports · 2021Article
- Noninvasive assessment of autonomic modulation of heart rate variability in the Ts65Dn mouse model of Down syndrome: A proof of principle study.Physiological reports · 2020Article
- Article
- The Association Between Diabetes Mellitus and Atrial Fibrillation: Clinical and Mechanistic Insights.Frontiers in physiology · 2019Review
- Article
- Autonomic dysfunction determines stress-induced cardiovascular and immune complications in mice.Journal of the American Heart Association · 2015Article
- Identifying Common Genetic Risk Factors of Diabetic Neuropathies.Frontiers in endocrinology · 2015Review
- A novel quantitative method for diabetic cardiac autonomic neuropathy assessment in type 1 diabetic mice.Journal of diabetes science and technology · 2014Article
- Glycogen synthase kinase-3β inhibition ameliorates cardiac parasympathetic dysfunction in type 1 diabetic Akita mice.Diabetes · 2014Article
- Increased inducibility of ventricular tachycardia and decreased heart rate variability in a mouse model for type 1 diabetes: effect of pravastatin.American journal of physiology. Heart and circulatory physiology · 2013Article
- Reduced ocular blood flow as an early indicator of diabetic retinopathy in a mouse model of diabetes.Investigative ophthalmology & visual science · 2012Article
- Na+/Ca2+ exchanger-1 protects against systolic failure in the Akitains2 model of diabetic cardiomyopathy via a CXCR4/NF-κB pathway.American journal of physiology. Heart and circulatory physiology · 2012Article
- The relationship among brain natriuretic peptide (BNP), cholesterol and lipoprotein.Heart Asia · 2012Article
- Effect of insulin and an erythropoietin-derived peptide (ARA290) on established neuritic dystrophy and neuronopathy in Akita (Ins2 Akita) diabetic mouse sympathetic ganglia.Experimental neurology · 2011Article
- Poly(ADP-ribose)polymerase inhibition counteracts renal hypertrophy and multiple manifestations of peripheral neuropathy in diabetic Akita mice.International journal of molecular medicine · 2011Article
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
rationaleDiabetic autonomic neuropathy (DAN), a major complication of diabetes mellitus, is characterized, in part, by impaired cardiac parasympathetic responsiveness. Parasympathetic stimulation of the heart involves activation of an acetylcholine-gated K+ current, I(KAch), via a (GIRK1)2/(GIRK4)2 K+ channel. Sterol regulatory element binding protein-1 (SREBP-1) is a lipid-sensitive transcription factor.
objectiveWe describe a unique SREBP-1-dependent mechanism for insulin regulation of cardiac parasympathetic response in a mouse model for DAN. METHODS AND
resultsUsing implantable EKG transmitters, we demonstrated that compared with wild-type, Ins2(Akita) type I diabetic mice demonstrated a decrease in the negative chronotropic response to carbamylcholine characterized by a 2.4-fold decrease in the duration of bradycardia, a 52+/-8% decrease in atrial expression of GIRK1 (P<0.01), and a 31.3+/-2.1% decrease in SREBP-1 (P<0.05). Whole-cell patch-clamp studies of atrial myocytes from Akita mice exhibited a markedly decreased carbamylcholine stimulation of I(KAch) with a peak value of -181+/-31 pA/pF compared with -451+/-62 pA/pF (P<0.01) in cells from wild-type mice. Western blot analysis of extracts of Akita mice demonstrated that insulin treatment increased the expression of GIRK1, SREBP-1, and I(KAch) activity in atrial myocytes from these mice to levels in wild-type mice. Insulin treatment of cultured atrial myocytes stimulated GIRK1 expression 2.68+/-0.12-fold (P<0.01), which was reversed by overexpression of dominant negative SREBP-1. Finally, adenoviral expression of SREBP-1 in Akita atrial myocytes reversed the impaired I(KAch) to levels in cells from wild-type mice.
conclusionsThese results support a unique molecular mechanism for insulin regulation of GIRK1 expression and parasympathetic response via SREBP-1, which might play a role in the pathogenesis of DAN in response to insulin deficiency in the diabetic heart.
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