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对诱导性低血糖的反调节反应。

Counter-regulatory responses to -induced hypoglycaemia.

作者信息

Salman Toyin Mohammed, Alagbonsi Isiaka Abdullateef, Sulaiman Sheu Oluwadare

机构信息

Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria.

Department of Physiology, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Huye, Rwanda.

出版信息

Metabol Open. 2020 Nov 5;8:100065. doi: 10.1016/j.metop.2020.100065. eCollection 2020 Dec.

DOI:10.1016/j.metop.2020.100065
PMID:33235989
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7670218/
Abstract

BACKGROUND

(TO) has many biological activities including blood glucose regulation. Thus, it is being used in the treatment of diabetes mellitus. TO has been shown to cause insulin-mediated hypoglycaemia, which leads to post-hypoglycaemic hyperglycaemia. However, the mechanism involved in the post-hypoglycaemic hyperglycaemia is still poorly understood.

OBJECTIVE

This research was designed to determine the response of glucoregulatory hormones and enzymes to TO treatment.

METHODS

Thirty-five male Wistar rats were divided into seven oral treatment groups (n = 5/group), which received either of 100 mg/kg or 200 mg/kg TO for 7-, 10- or 14 days.

RESULTS

The 7-day treatment with TO significantly increased the levels of insulin, glucagon, and glucose-6-phosphatase (G6Pase) activity but decreased the levels of glucose, adrenaline, and glucokinase (GCK) activity. The 10-day treatment with 100 mg/kg TO increased glucose and decreased GCK activity while 200 mg/kg for the same duration increased glucose, insulin, GCK and G6Pase activities but reduced glucagon. The 14-day treatment with 100 mg/kg TO decreased glucose and glucagon but increased cortisol, while 200 mg/kg TO for same duration increased insulin, but reduced glucagon and GCK activity.

CONCLUSION

The TO's post-hypoglycaemic hyperglycaemia results from increased glucagon and G6Pase activity, and reduced GCK activity. Moreover, the glucagon response mainly depends on glucose rather than insulin.

摘要

背景

(某种物质,此处未明确给出具体名称,暂用TO指代)具有多种生物活性,包括调节血糖。因此,它正被用于治疗糖尿病。已表明TO会导致胰岛素介导的低血糖,进而引发低血糖后高血糖。然而,低血糖后高血糖所涉及的机制仍知之甚少。

目的

本研究旨在确定糖调节激素和酶对TO治疗的反应。

方法

将35只雄性Wistar大鼠分为7个口服治疗组(每组n = 5),分别接受100 mg/kg或200 mg/kg的TO治疗7天、10天或14天。

结果

TO治疗7天显著提高了胰岛素、胰高血糖素水平以及葡萄糖-6-磷酸酶(G6Pase)活性,但降低了葡萄糖、肾上腺素水平以及葡萄糖激酶(GCK)活性。100 mg/kg的TO治疗10天使葡萄糖水平升高且GCK活性降低,而相同疗程200 mg/kg的TO则使葡萄糖、胰岛素、GCK和G6Pase活性升高,但胰高血糖素水平降低。100 mg/kg的TO治疗14天使葡萄糖和胰高血糖素水平降低,但皮质醇水平升高,而相同疗程200 mg/kg的TO使胰岛素水平升高,但胰高血糖素和GCK活性降低。

结论

TO导致的低血糖后高血糖是由胰高血糖素和G6Pase活性增加以及GCK活性降低所致。此外,胰高血糖素的反应主要取决于葡萄糖而非胰岛素。

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Glucose controls glucagon secretion by directly modulating cAMP in alpha cells.葡萄糖通过直接调节α细胞中的 cAMP 来控制胰高血糖素的分泌。
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The Central Role of Glucokinase in Glucose Homeostasis: A Perspective 50 Years After Demonstrating the Presence of the Enzyme in Islets of Langerhans.葡萄糖激酶在葡萄糖稳态中的核心作用:自证实该酶存在于胰岛50年后的观点。
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