Changes in electrical properties of detrusor smooth muscle in the STZ (streptozotocin)–diabetic rat

Venkateswarlu, K; Santizo, Cristian; Zhao, Wei; Kuo, Enoch; Shenk, G; Melman, Arnold; Christ, George J.

doi:10.1016/s0090-4295(01)01040-8

Cited by 4 publications

(3 citation statements)

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“…Therefore, a defect in channel activation, function or expression may occur as a consequence of the diabetic environment. Despite the large number of studies from diabetic animals reporting impaired contractility, few studies have investigated the underlying mechanisms or measured intracellular Ca 2+ .Studies of resting membrane potential show no significant changes with diabetes [36, 44, 45], suggesting that K + channel activity is unaltered. Reduction in release of Ca 2+ from the sarcoplasmic reticulum, Ca 2+ sparks, and activators of Ca-activated K channel (BK) channels was reported in coronary micro-vessels with diabetes in pigs [46].…”

Section: Discussionmentioning

confidence: 99%

Diabetes is associated with impairment of uterine contractility and high Caesarean section rate

et al. 2011

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Aims/hypothesisThe prevalence of births worldwide complicated by diabetes mellitus is increasing. In the UK, for example, <25% of diabetic women have a non-instrumental vaginal delivery. Strikingly, more than half the Caesarean sections (CS) in these patients are non-elective, but the reasons for this are not understood. We have tested the hypothesis that poor myometrial contractility as a consequence of the disease contributes to this high CS rate.MethodsWe compared spontaneous, high K depolarisation and oxytocin-induced contractions from diabetic and matched control patients having an elective CS. To investigate the mechanism of any differences we measured intracellular Ca, and performed western blotting and compared the tissues histologically.ResultsThere was significantly decreased contraction amplitude and duration in uteri from diabetic compared with control patients, even when possible confounders such as BMI were analysed. Reduced intracellular calcium signals and expression of calcium entry channels were found in uteruses from diabetic patients, which, along with a reduction in muscle content found on histological examination, could explain the reduced force. Myometrium from diabetic patients was responsive to oxytocin, but still did not reach the levels found in non-diabetic patients.Conclusions/interpretationsThese are the first data investigating myometrium in diabetic patients and they support the hypothesis that there is poorer contractility even in the presence of oxytocin. The underlying mechanism is related to reduced Ca channel expression and intracellular calcium signals and a decrease in muscle mass. We conclude that these factors significantly contribute to the increased emergency CS rate in diabetic patients.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-011-2371-6) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

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Section: Discussionmentioning

confidence: 99%

Diabetes is associated with impairment of uterine contractility and high Caesarean section rate

et al. 2011

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“…Two or 8 wk of STZ-diabetes was induced in 18 animals via a single intraperitoneal injection of STZ (35 mg/kg) dissolved in citrate buffer (60 ml of 0.1 mol/l citric acid and 40 ml of 0.2 mol/l Na 2 HPO 4 , pH 4.6). Age-matched control animals received an injection of vehicle only [23]. One group of 8-wk diabetic animals was treated daily with 2 units insulin sc (Eli Lilly, IN, USA) for 1 wk.…”

Section: Animalsmentioning

confidence: 99%

Diabetes-Induced Changes in the Alternative Splicing of the Slo Gene in Corporal Tissue

et al. 2007

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“…Rats were fed Purina laboratory rodent chow ad libitum and housed individually with a 0700 -1900 light cycle. Rats were made diabetic by a single intraperitoneal injection of streptozotocin (STZ; 35 mg/kg) dissolved in citrate buffer (60 ml of 0.1 mol/l citric acid and 40 ml of 0.2 mol/l Na 2HPO4 pH 4.6), as previously described (17). Agematched control (AMC) animals received an injection of vehicle only.…”

Section: Methodsmentioning

confidence: 99%

Reversal of diabetic vasculopathy in a rat model of type 1 diabetes by opiorphin-related peptides

Calenda

Tong²,

Kanika³

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Diabetes results in a myriad of vascular complications, often referred to as diabetic vasculopathy, which encompasses both microvascular [erectile dysfunction (ED), retinopathy, neuropathy, and nephropathy] and macrovascular complications (hypertension, coronary heart disease, and myocardial infarction). In diabetic animals and patients with ED, there is decreased opiorphin or opiorphin-related gene expression in corporal tissue. Both opiorphin and the rat homologous peptide sialorphin are found circulating in the plasma. In the present study, we investigated if diabetes induced changes in plasma sialorphin levels and if changes in these levels could modulate the biochemistry and physiology of vascular smooth muscle. We show that circulating sialorphin levels are reduced in a rat model of type I diabetes. Intracorporal injection of plasmids expressing sialorphin into diabetic rats restores sialorphin levels to those seen in the blood of nondiabetic animals and results in both improved erectile function and blood pressure. Sialorphin modulated the ability of C-type natriuretic peptide to relax both corporal and aortic smooth muscle strips and of bradykinin to regulate intracellular calcium levels in both corporal and aortic smooth muscle cells. We have previously shown that expression of genes encoding opiorphins is increased when erectile function is improved. Our findings thus suggest that by affecting circulating levels of opiorphin-related peptides, proper erectile function is not only an indicator but also a modulator of overall vascular health of a man.

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Changes in electrical properties of detrusor smooth muscle in the STZ (streptozotocin)–diabetic rat

Cited by 4 publications

References 0 publications

Diabetes is associated with impairment of uterine contractility and high Caesarean section rate

Diabetes is associated with impairment of uterine contractility and high Caesarean section rate

Diabetes-Induced Changes in the Alternative Splicing of the Slo Gene in Corporal Tissue

Reversal of diabetic vasculopathy in a rat model of type 1 diabetes by opiorphin-related peptides

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