A new model of experimental diabetic cardiomyopathy using combination of multiple doses of anomer-equilibrated streptozotocin and high fat diet: sex matters.

IF 6.2 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Diabetes Pub Date : 2025-01-21 DOI:10.2337/db24-0385
Loucia Karatzia, Fenn Cullen, Megan Young, Shing Hei Lam, Valle Morales, Katiuscia Bianchi, Sian M. Henson, Dunja Aksentijevic
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Abstract

Diabetes mellitus (DM) leads to a more rapid development of DM cardiomyopathy (dbCM) and progression to heart failure in women than men. Combination of high-fat diet (HFD) and freshly-injected streptozotocin (STZ) has been widely used for DM induction, however emerging data shows that anomer-equilibrated STZ produces an early onset and robust DM model. We designed a novel protocol utilising a combination of multiple doses of anomer-equilibrated STZ injections and HFD to develop a stable murine DM model featuring dbCM analogous to humans. Furthermore, we examined the impact of biological sex on the evolution of cardiometabolic dysfunction in DM. Our study included six experimental protocols (8 weeks) in male and female C57BL/6J mice (n=109): Fresh STZ+HFD, Anomer-equilibrated STZ+HFD, HFD, Fresh STZ, Anomer-equilibrated STZ, Control diet+vehicle. Animals were characterised by extensive phenotyping in vivo and ex vivo. Anomer-equilibrated STZ+HFD led to induction of stable experimental murine DM characterised by impaired glucose homeostasis, cardiometabolic dysfunction and altered metabolome of liver, skeletal muscle, kidney and plasma. dbCM was more severe in female mice including systolic dysfunction and reduced cardiac energy reserve. This study established a novel, robust model of inducible murine DM and emphasised the impact of biological sex on DM progression and severity.
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多剂量氨基平衡链脲佐菌素和高脂饮食联合治疗实验性糖尿病心肌病的新模型:性别问题
糖尿病(DM)导致女性比男性更快地发展为DM心肌病(dbCM)并进展为心力衰竭。高脂肪饮食(HFD)和新鲜注射链脲佐菌素(STZ)的组合已被广泛用于DM诱导,但新数据显示,异位平衡的STZ可产生早发且稳健的DM模型。我们设计了一种新的方案,利用多剂量异温平衡STZ注射和HFD的组合来开发具有类似人类dbCM的稳定小鼠DM模型。此外,我们还研究了生理性别对糖尿病心脏代谢功能障碍进化的影响。我们的研究包括6个实验方案(8周),在雄性和雌性C57BL/6J小鼠(n=109)中:新鲜STZ+HFD、异常平衡STZ+HFD、HFD、新鲜STZ、异常平衡STZ、对照饮食+对照物。动物的特点是体内和体外广泛的表型。异常平衡的STZ+HFD诱导了稳定的实验小鼠DM,其特征是葡萄糖稳态受损、心脏代谢功能障碍以及肝脏、骨骼肌、肾脏和血浆代谢组改变。雌性小鼠dbCM更严重,包括收缩功能障碍和心脏能量储备减少。本研究建立了一种新的、稳健的诱导型小鼠糖尿病模型,并强调了生理性别对糖尿病进展和严重程度的影响。
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来源期刊
Diabetes
Diabetes 医学-内分泌学与代谢
CiteScore
12.50
自引率
2.60%
发文量
1968
审稿时长
1 months
期刊介绍: Diabetes is a scientific journal that publishes original research exploring the physiological and pathophysiological aspects of diabetes mellitus. We encourage submissions of manuscripts pertaining to laboratory, animal, or human research, covering a wide range of topics. Our primary focus is on investigative reports investigating various aspects such as the development and progression of diabetes, along with its associated complications. We also welcome studies delving into normal and pathological pancreatic islet function and intermediary metabolism, as well as exploring the mechanisms of drug and hormone action from a pharmacological perspective. Additionally, we encourage submissions that delve into the biochemical and molecular aspects of both normal and abnormal biological processes. However, it is important to note that we do not publish studies relating to diabetes education or the application of accepted therapeutic and diagnostic approaches to patients with diabetes mellitus. Our aim is to provide a platform for research that contributes to advancing our understanding of the underlying mechanisms and processes of diabetes.
期刊最新文献
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