Synaptic degradation of cardiac autonomic nerves in streptozotocin-induced diabetic rats

Sanyal, Shamarendra; Wada, Tomoyuki; Yamabe, Motoko; Anai, Hirofumi; Miyamoto, Shinj̀i; Shimada, Toshio; Ono, Katsushige

doi:10.1016/j.pathophys.2012.08.002

Cited by 10 publications

(12 citation statements)

References 38 publications

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“…In patients with diabetic neuropathy [ 26 ] and the spontaneously diabetic BB-Wistar-rat [ 27 ], mitochondrial accumulation of glycogen particles was observed. In experimental diabetic animals, the loss of vesicles in presynapse [ 28 ] and autonomic nerve endings [ 29 ] was reported. Therefore, the alterations in components of bead other than mitochondria might influence the density and size of bead.…”

Section: Discussionmentioning

confidence: 99%

The Expanded Bead Size of Corneal C-Nerve Fibers Visualized by Corneal Confocal Microscopy Is Associated with Slow Conduction Velocity of the Peripheral Nerves in Patients with Type 2 Diabetes Mellitus

Ishibashi¹,

Kojima²,

Taniguchi³

et al. 2016

Journal of Diabetes Research

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This study aims to establish the corneal nerve fiber (CNF) morphological alterations in a large cohort of type 2 diabetic patients and to investigate the association between the bead size, a novel parameter representing composite of accumulated mitochondria, glycogen particles, and vesicles in CNF, and the neurophysiological dysfunctions of the peripheral nerves. 162 type 2 diabetic patients and 45 healthy control subjects were studied in detail with a battery of clinical and neurological examinations and corneal confocal microscopy. Compared with controls, patients had abnormal CNF parameters. In particular the patients had reduced density and length of CNF and beading frequency and increased bead size. Alterations in CNF parameters were significant even in patients without neuropathy. The HbA1c levels were tightly associated with the bead size, which was inversely related to the motor and sensory nerve conduction velocity (NCV) and to the distal latency period of the median nerve positively. The CNF density and length positively correlated with the NCV and amplitude. The hyperglycemia-induced expansion of beads in CNF might be a predictor of slow NCV in peripheral nerves in type 2 diabetic patients.

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Section: Discussionmentioning

confidence: 99%

The Expanded Bead Size of Corneal C-Nerve Fibers Visualized by Corneal Confocal Microscopy Is Associated with Slow Conduction Velocity of the Peripheral Nerves in Patients with Type 2 Diabetes Mellitus

Ishibashi¹,

Kojima²,

Taniguchi³

et al. 2016

Journal of Diabetes Research

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“…Untreated STZ‐induced chronic diabetic rats showed significant increases in SBP, DBP and MAP, but a decrease in heart rate, when compared to normal control rats. The decrease in heart rate of STZ‐induced diabetic rats was also reported by previous investigators (Sanyal et al ., , Li et al ., ). It has been proposed that in the process of STZ induced diabetes, the vagus nerve and sympathetic nerve are both injured resulting in sympathetic‐vagal imbalance which begins with parasympathetic nerve failure in the very early stages followed by sympathetic nerve failure in the later stages, finally causing a decrease in heart rate.…”

Section: Discussionmentioning

confidence: 97%

“…It has been proposed that in the process of STZ induced diabetes, the vagus nerve and sympathetic nerve are both injured resulting in sympathetic-vagal imbalance which begins with parasympathetic nerve failure in the very early stages followed by sympathetic nerve failure in the later stages, finally causing a decrease in heart rate. Another possibility is that bradycardia may be because of alterations of electrical activity in sinus node as a result of hyperglycemia (Sanyal et al, 2012). Hypertension is a common complication in chronic diabetic patients and its pathogenesis is multifactorial.…”

Section: Discussionmentioning

confidence: 99%

Protocatechuic Acid Restores Vascular Responses in Rats With Chronic Diabetes Induced by Streptozotocin

et al. 2015

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Oxidative stress has been shown to play an important role in development of vascular dysfunction in diabetes. Protocatechuic acid (PCA) has been reported to exert antioxidant and anti-hyperglycemic activities. Diabetes was induced in male Sprague-Dawley rats by a single intraperitoneal injection of 50 mg/kg streptozotocin (STZ). The rats were maintained in a state of hyperglycemia for 12 weeks. Then, PCA (50 or 100 mg/kg/day) was administered orally or insulin (4 U/kg/day) was subcutaneous injected to the rats for 6 weeks. Blood pressure, vascular responses to vasoactive agents, vascular superoxide production, blood glucose, insulin, malondialdehyde, nitric oxide and antioxidant enzymes were examined. The diabetic rats showed weight loss, insulin deficiency, hyperglycemia, increased oxidative stress, decreased plasma nitric oxide, elevated blood pressure, increased vascular response to phenylephrine and decreased vascular responses to acetylcholine and sodium nitroprusside. PCA significantly decreased blood glucose and oxidative stress, and increased plasma nitric oxide in diabetic rats. Interestingly, PCA treatment restored blood pressure and vascular reactivity, and antioxidant enzyme activity diabetic rats. This study provides the first evidence of the efficacy of PCA in restoring the vascular reactivity of diabetic rats. The mechanism of action may be associated with an alleviation of oxidative stress.

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“…To understand the complex nature and consequences of CAN, its progression has been investigated in a variety of animal models (reviewed in ). While studies reported a decrease in HRV, some reported neuropathy of all autonomic nerve fibres, some of only sympathetic fibres and some no neuropathy at all, but rather an increase in cholinergic nerve density . Heart rate variability analysis on the db/db mouse using telemetry has both shown unchanged HRV at 8‐9 weeks of age and reduced HRV at 12 weeks of age in two separate studies; however, few studies have directly investigated the presence of CAN in the db/db mouse.…”

Section: Discussionmentioning

confidence: 99%

Aberrant sinus node firing during β‐adrenergic stimulation leads to cardiac arrhythmias in diabetic mice

et al. 2020

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Aim: Cardiovascular complications, including cardiac arrhythmias, result in high morbidity and mortality in patients with type-2 diabetes mellitus (T2DM). Clinical and experimental data suggest electrophysiological impairment of the natural pacemaker of the diabetic heart. The present study examined sinoatrial node (SAN) arrhythmias in a mouse model of T2DM and physiologically probed their underlying cause. Methods: Electrocardiograms were obtained from conscious diabetic db/db and lean control db/+ mice. In vivo SAN function was probed through pharmacological autonomic modulation with isoprenaline, atropine and carbachol. Blood pressure stability and heart rate variability (HRV) were evaluated. Intrinsic SAN function was evaluated through ex vivo imaging of spontaneous Ca 2+ transients in isolated SAN preparations. Results: While lean control mice showed constant RR intervals during isoprenaline challenge, the diabetic mice experienced SAN arrhythmias with large RR fluctuations in a dose-dependent manner. These arrhythmias were completely abolished by atropine pre-treatment, while carbachol pretreatment significantly increased SAN arrhythmia frequency in the diabetic mice. Blood pressure and HRV were comparable in db/db and db/+ mice, suggesting that neither augmented baroreceptor feedback nor autonomic neuropathy is a likely arrhythmia mechanism. Cycle length response to isoprenaline was comparable in isolated SAN preparations from db/db and db/+ mice; however, Ca 2+ spark frequency was significantly increased in db/db mice compared to db/+ at baseline and after isoprenaline. Conclusion: Our results demonstrate a dysfunction of cardiac pacemaking in an animal model of T2DM upon challenge with a β-adrenergic agonist. Ex vivo, higher Ca 2+ spark frequency is present in diabetic mice, which may be directly linked to in vivo arrhythmias. K E Y W O R D Sautonomic nervous system, baroreflex, calcium, electrophysiology, isoprenaline, type-2 diabetes

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Synaptic degradation of cardiac autonomic nerves in streptozotocin-induced diabetic rats

Cited by 10 publications

References 38 publications

The Expanded Bead Size of Corneal C-Nerve Fibers Visualized by Corneal Confocal Microscopy Is Associated with Slow Conduction Velocity of the Peripheral Nerves in Patients with Type 2 Diabetes Mellitus

The Expanded Bead Size of Corneal C-Nerve Fibers Visualized by Corneal Confocal Microscopy Is Associated with Slow Conduction Velocity of the Peripheral Nerves in Patients with Type 2 Diabetes Mellitus

Protocatechuic Acid Restores Vascular Responses in Rats With Chronic Diabetes Induced by Streptozotocin

Aberrant sinus node firing during β‐adrenergic stimulation leads to cardiac arrhythmias in diabetic mice

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