Ashish K Rehni, Sunjoo Cho, Allen Liu, Jonathan Lo, Stephanie S Kim, Nathalie Khoury, Miguel A Perez-Pinzon, Wenche Jy, Kunjan R Dave
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引用次数: 0
Abstract
Aims: Diabetes is a widespread disease associated with long-term complications. Treatment of diabetes alleviates these complications but cause an increased risk of recurrent hypoglycemia (RH). Hypoglycemia exposure increases the risk of cardiovascular events by an unknown mechanism. Since the effect of mild/moderate hypoglycemia on thrombosis is unknown, we studied the effect of RH exposure on platelet function and thrombosis in insulin-treated diabetic (ITD) rats.
Materials and methods: ITD rats were randomized to either control or hypoglycemia groups. First, we determined the minimum duration and frequency of RH exposure that increases the risk of thrombosis and the time window after a single hypoglycemic episode (SH)/RH exposure with increased risk of thrombosis in male ITD rats. Next, we confirmed whether RH exposure increases the risk of thrombosis in female ITD rats. Subsequently, we evaluated the impact of RH exposure on platelet susceptibility to aggregation and platelet gene expression.
Results: One hour hypoglycemia increased the clot weight and the effect of SH and RH on thrombosis lasted for at least 1 and 7 days post-exposure, respectively. A minimum frequency of twice-a-week hypoglycemia exposure for 6 weeks increased the risk of thrombosis in male ITD rats. Increased susceptibility of platelet activation was observed in RH-exposed male ITD rats. Lastly, we identified RH-induced alterations in the platelet transcriptome in male ITD rats. We also confirmed that RH exposure increases the risk of thrombosis in female rats.
Conclusions: Understanding the mechanism of RH-induced platelet activation and thrombosis may help limit thrombotic complications in diabetes.
期刊介绍：
Diabetes, Obesity and Metabolism is primarily a journal of clinical and experimental pharmacology and therapeutics covering the interrelated areas of diabetes, obesity and metabolism. The journal prioritises high-quality original research that reports on the effects of new or existing therapies, including dietary, exercise and lifestyle (non-pharmacological) interventions, in any aspect of metabolic and endocrine disease, either in humans or animal and cellular systems. ‘Metabolism’ may relate to lipids, bone and drug metabolism, or broader aspects of endocrine dysfunction. Preclinical pharmacology, pharmacokinetic studies, meta-analyses and those addressing drug safety and tolerability are also highly suitable for publication in this journal. Original research may be published as a main paper or as a research letter.
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