Combined Metformin and Baricitinib Therapy Attenuates Inflammation in STZ-Induced Diabetic Rats via AMPK/JAK–STAT Pathway Crosstalk

IF 2.6 Q3 ENDOCRINOLOGY & METABOLISM
Mostafa Allahyari, AbdolJalal Marjani, Marie Saghaeian Jazi, Mehrdad Jahanshahi
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Abstract

Background

Chronic inflammation is a critical factor contributing to diabetes complications. Baricitinib inhibits JAK–STAT signalling, which can contribute to an anti-inflammatory effect. Similarly, metformin demonstrates anti-inflammatory properties by activating the AMPK–SIRT pathway and suppressing the NF-ᴋB signalling pathway. Here, we explored the effects of the coadministration of metformin and baricitinib in diabetic rats.

Methods

Streptozotocin (40 mg/kg body weight) was administered to rats to develop diabetes after 2 weeks of 10% fructose solution consumption. The rats were treated with baricitinib (0.5, 2.5 and 5 mg/kg) and 150 mg/kg metformin for 1 month. A dose of 0.5 mg/kg baricitinib was chosen for combination therapy with metformin.

Key Findings

Baricitinib induced significant weight loss at all three doses (p ≤ 0.05) and significantly increased lipid profile parameters in comparison to the diabetic control group (p ≤ 0.05). Pancreatic NF-ᴋB levels and HOMA-IR were meaningfully reduced in all treatment groups (p ≤ 0.01). Metformin and combination therapy significantly reduced serum TNF-α levels (p ≤ 0.05). Furthermore, baricitinib at different doses and combination therapy significantly elevated serum IL-10 levels (p ≤ 0.05). Additionally, combination therapy significantly upregulated the liver expression of NF-ᴋB, SOCS1, SOCS3, AMPK and SIRT-1 (p ≤ 0.01).

Conclusion

Our results suggest that the coadministration of metformin with baricitinib reduces insulin resistance, improves histopathological alterations in the liver and pancreatic islet cells and counteracts the adverse effects of baricitinib on the lipid profile in diabetic rats. These findings hold particular significance for patients undergoing baricitinib treatment.

Abstract Image

二甲双胍联合巴西替尼治疗通过AMPK/ JAK-STAT通路串扰减轻stz诱导的糖尿病大鼠炎症
慢性炎症是导致糖尿病并发症的重要因素。Baricitinib抑制JAK-STAT信号传导,这有助于抗炎作用。类似地,二甲双胍通过激活AMPK-SIRT通路和抑制NF- k - B信号通路显示出抗炎特性。在这里,我们探讨了二甲双胍和巴西替尼共同给药对糖尿病大鼠的影响。方法采用链脲佐菌素(40 mg/kg体重)治疗大鼠糖尿病。大鼠分别给予巴西替尼(0.5、2.5、5 mg/kg)和二甲双胍150 mg/kg治疗1个月。巴西替尼与二甲双胍联合治疗,剂量为0.5 mg/kg。与糖尿病对照组相比,Baricitinib在三个剂量下均能显著减轻体重(p≤0.05),并显著增加血脂参数(p≤0.05)。各治疗组胰腺NF- s - B水平和HOMA-IR均显著降低(p≤0.01)。二甲双胍联合用药显著降低血清TNF-α水平(p≤0.05)。此外,巴西替尼不同剂量及联合治疗均显著提高血清IL-10水平(p≤0.05)。此外,联合治疗显著上调了肝脏中NF- salb、SOCS1、SOCS3、AMPK和SIRT-1的表达(p≤0.01)。结论二甲双胍联合巴西替尼可降低糖尿病大鼠的胰岛素抵抗,改善肝脏和胰岛细胞的组织病理学改变,抵消巴西替尼对糖尿病大鼠血脂的不良影响。这些发现对接受巴西替尼治疗的患者具有特别的意义。
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来源期刊
Endocrinology, Diabetes and Metabolism
Endocrinology, Diabetes and Metabolism Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
5.00
自引率
0.00%
发文量
66
审稿时长
6 weeks
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