Anti-diabetic Role of Adropin in Streptozotocin Induced Diabetic Rats via Alteration of PI3K/Akt and Insulin Signaling Pathway

He, Liyun; Zhang, Fengjiao; Li, Hao-Yun; Li, Lei; Song, Lina; Mao, Yu; Li, Jing; Liu, Hongmei; Li, Fengli; Xu, Lina; Huo, Yajie; Wang, Huanhuan; Luo, Fang; Kang, Zhiqiang

doi:10.5650/jos.ess21019

Cited by 8 publications

(5 citation statements)

References 20 publications

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“…Because insulin resistance is caused by insulin signaling disorders, it is necessary to improve the insulin signaling pathway [41]. The insulin signaling pathway is involved in maintaining glucose homeostasis [42]. Insulin receptor substrate 1 (IRS-1) is one of the major substrates of insulin receptor kinase.…”

Section: Discussionmentioning

confidence: 99%

HMC Ameliorates Hyperglycemia via Acting PI3K/AKT Pathway and Improving FOXO1 Pathway in ob/ob Mice

2023

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Type 2 diabetes is a disease characterized by hyperglycemia and is a growing health problem worldwide. Since many known diabetes drugs are side effects, it is necessary to develop natural substances with guaranteed safety. HM-chromanone isolated from Portulaca oleracea L. is a homoisoflavonoid compound. We investigated the effects of HM-chromanone on hyperglycemia and its mechanism in C57BL/6J ob/ob mice. C57BL/6J-Jms Slc mice were used as the control group, and C57BL/6J-ob/ob mice were divided into three groups: ob/ob (control), metformin (Met; positive control), and HM-chromanone (HMC). Fasting blood glucose was lower in the HMC group than those in the ob/ob group. Insulin resistance was improved by reducing HbA1c, plasma insulin, and HOMA-IR levels in the HMC group. HMC administration decreased the phosphorylation of IRS-1ser307 and increased the phosphorylation of IRS-1tyr612, PI3K, phosphorylation of AKTser473, and PM-GLUT4 in the skeletal muscles of ob/ob mice, indicating improved insulin signaling. HMC administration also increased the phosphorylation of FOXO1 in the liver of ob/ob mice. This inhibited PEPCK and G6pase involved in gluconeogenesis and regulated phosphorylation of glycogen synthase kinase 3β and glycogen synthase involved in glycogen synthesis. In conclusion, HM-chromanone ameliorates hyperglycemia by PI3K/AKT and improves the FOXO1 in ob/ob mice.

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Section: Discussionmentioning

confidence: 99%

HMC Ameliorates Hyperglycemia via Acting PI3K/AKT Pathway and Improving FOXO1 Pathway in ob/ob Mice

2023

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“…In animal studies, adropin overexpression or adropin treatment significantly ameliorated insulin resistance, enhanced glucose tolerance and improved glycolipid metabolism in diet-induced obese mice with insulin resistance [ 3 , 4 , 20 ]. In streptozotocin (STZ)-induced diabetic rats, adropin administration could improve glycemic levels, body weight, insulin levels, hepatic glycogen and carbohydrate enzymes in a dose-dependent manner, which were almost close to those of the normal control [ 21 ]. Mechanistically, several studies have found that adropin can exert beneficial metabolic effects through different mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…Adropin enhanced glucose uptake via increased translocation of peroxisome proliferator-activated receptor γ (PPARγ) and glucose transpoter-4 (GLUT-4) to the plasma membrane. Secondly, adropin exerted antidiabetic effect through the AMPK pathway, which was mainly reflected in the elevations of AMPK levels and acetyl CoA carboxylase (ACC) phosphorylation in diabetic rat liver [ 21 ]. Furthermore, adropin enhanced hepatic intracellular signaling actions that were involved in insulin-mediated glucose homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Adropin by Sitagliptin monotherapy in participants with newly diagnosed type 2 Diabetes

Wang

Zhang

et al. 2022

BMC Endocr Disord

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Background Adropin is a potent metabolic regulator of insulin sensitivity and glycolipid metabolism. The present study investigated the effects of sitagliptin on adropin and metabolic parameters in participants with newly diagnosed type 2 diabetes (T2D). Methods Thirty-five participants newly-diagnosed with T2D were prescribed sitagliptin 100 mg once daily for 17 weeks. Twenty-eight age-, sex-, and BMI-matched healthy subjects were included as the control group. Adropin and clinical parameters were assessed at baseline and after treatment. Results At baseline, serum adropin levels were lower in T2D participants than in the healthy individuals (3.12 ± 0.73 vs. 5.90 ± 1.22 ng/ml, P < 0.01). Serum adropin levels were significantly higher in T2D patients after sitagliptin treatment (4.97 ± 1.01 vs. 3.12 ± 0.73 ng/ml, P < 0.01). The changes in serum adropin levels after sitagliptin treatment were associated with the improvements of fasting blood glucose (FBG) (β = − 0.71, P < 0.01), glycosylated hemoglobin (HbA1c) (β = − 0.44, P < 0.01) and homeostatic model assessment of β-cell function (HOMA-β) (β = 9.02, P < 0.01). Conclusions Sitagliptin treatment could significantly increase serum adropin levels in participants with newly diagnosed T2D. The increase in serum adropin levels could be associated with the amelioration of glucose metabolism, which might be involved in beneficial glucose-lowering mechanisms of sitagliptin. Trial registration Clinicaltrials.gov, NCT04495881. Retrospectively registered on 03/08/2020.

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“…(Rais et al ., 2023) and glibenclamide (GL; 10 mg/kg, b.w.) as a standard drug (He et al ., 2021; Nguyen, Pham, Luong, Le, & Vo, 2020) as five treatment regimens were given separately to five groups of animals. For appropriate comparison, two separate nondiabetic groups were designed to receive normal saline and SAC/TAU combination as controls.…”

Section: Methodsmentioning

confidence: 99%

S-allyl cysteine and Taurine attenuate diabetic nephropathy in rats via the inhibition of oxidative stress and recovering histopathological changes

Rais

Ved²,

Rahim³

et al. 2023

AGJSR

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PurposeRenal failure is an end-stage consequence after persistent hyperglycemia during diabetic nephropathy (DN), and the etiology of DN has been linked to oxidative stress. The purpose of this research was to determine the beneficial synergistic effects of S-Allyl Cysteine (SAC) and Taurine (TAU) on oxidative damage in the kidneys of type 2 diabetic rats induced by hyperglycemia.Design/methodology/approachExperimental diabetes was developed by administering intraperitoneal single dose of streptozotocin (STZ; 65 mg/kg) with nicotinamide (NA; 230 mg/kg) in adult rats. Diabetic and control rats were treated with SAC (150 mg/kg), TAU (200 mg/kg) or SAC and TAU combination (75 + 100 mg/kg) for four weeks. The estimation of body weight, fasting blood glucose (FBG), oral glucose tolerance test (OGTT), oxidative stress markers along with kidney histopathology was done to investigate the antidiabetic potential of SAC/TAU in the NA/STZ diabetic group.FindingsThe following results were obtained for the therapeutic efficacy of SAC/TAU: decrease in blood glucose level, decreased level of thiobarbituric acid reactive substances (TBARS) and increased levels of GSH, glutathione-s-transferase (GST) and catalase (CAT). SAC/TAU significantly modulated diabetes-induced histological changes in the kidney of rats.Originality/valueSAC/TAU combination therapy modulated the oxidative stress markers in the kidney in diabetic rat model and also prevented oxidative damage as observed through histopathological findings.

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Anti-diabetic Role of Adropin in Streptozotocin Induced Diabetic Rats via Alteration of PI3K/Akt and Insulin Signaling Pathway

Cited by 8 publications

References 20 publications

HMC Ameliorates Hyperglycemia via Acting PI3K/AKT Pathway and Improving FOXO1 Pathway in ob/ob Mice

HMC Ameliorates Hyperglycemia via Acting PI3K/AKT Pathway and Improving FOXO1 Pathway in ob/ob Mice

Regulation of Adropin by Sitagliptin monotherapy in participants with newly diagnosed type 2 Diabetes

S-allyl cysteine and Taurine attenuate diabetic nephropathy in rats via the inhibition of oxidative stress and recovering histopathological changes

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