A novel recombinant peptide INSR-IgG4Fc (Yiminsu) restores insulin sensitivity in experimental insulin resistance models

Jing Wang, Zhe Shi, Tao Zou, Min Xu Zou, Hui Xian Yang, Cai Ping Zhang, De Biao Xiang, Li Mei Lin, Hui Yu Liu, Deyu Fang, Duan Fang Liao

Research output: Contribution to journalArticle

Abstract

Type 2 diabetes mellitus (T2DM) is a chronic degenerative endocrine and metabolic disease with high mortality and morbidity, yet lacks effective therapeutics. We recently generated a novel fusion peptide INSR-IgG4Fc, Yiminsu (YMS), to facilitate the high-affinity binding and transportation of insulin. Thus, the aim of the present study was to determine whether the novel recombinant peptide, YMS, could contribute to restoring insulin sensitivity and glycaemic control in insulin resistance models and revealing its underlying mechanism. Palmitic acid (PA)-treated LO2 cells and high fat diet (HFD)-fed mice were treated with YMS. Therapeutic effects of YMS were measured using Western blotting, ELISA, qPCR, Histology and transmission electron microscopy. We observed that YMS treatment effectively improved insulin signaling in PA-treated LO2 cells and HFD-fed mice. Notably, YMS could significantly reduce serum levels of glucose, triglycerides, fatty acids and cholesterol without affecting the serum insulin levels. Moreover, our data demonstrated that YMS could restore glucose and lipid homeostasis via facilitating insulin transportation and reactivating PI3K/Akt signaling in both PA-treated cells and liver, gastrocnemius and brown fat of HFD-fed mice. Additionally, we noticed that the therapeutic effects of YMS was similar as rosiglitazone, a well-recognized insulin sensitizer. Our findings suggested that YMS is a potentially candidate for pharmacotherapy for metabolic disorders associated with insulin resistance, particularly in T2DM.

LanguageEnglish (US)
Pages1276-1286
Number of pages11
JournalBiomedicine and Pharmacotherapy
Volume109
DOIs
StatePublished - Jan 1 2019

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Type 2 Diabetes Mellitus
Insulin Resistance
Palmitic Acid
Insulin
High Fat Diet
Peptides
rosiglitazone
Therapeutic Uses
Endocrine System Diseases
Glucose
Brown Adipose Tissue
Metabolic Diseases
Serum
Transmission Electron Microscopy
Phosphatidylinositol 3-Kinases
Histology
Triglycerides
Homeostasis
Fatty Acids
Western Blotting

Keywords

  • Insulin resistance
  • PI3K-Akt pathway
  • Recombinant peptide
  • Type 2 diabetes mellitus
  • Yiminsu

ASJC Scopus subject areas

  • Pharmacology

Cite this

Wang, Jing ; Shi, Zhe ; Zou, Tao ; Zou, Min Xu ; Yang, Hui Xian ; Zhang, Cai Ping ; Xiang, De Biao ; Lin, Li Mei ; Liu, Hui Yu ; Fang, Deyu ; Liao, Duan Fang. / A novel recombinant peptide INSR-IgG4Fc (Yiminsu) restores insulin sensitivity in experimental insulin resistance models. In: Biomedicine and Pharmacotherapy. 2019 ; Vol. 109. pp. 1276-1286.
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A novel recombinant peptide INSR-IgG4Fc (Yiminsu) restores insulin sensitivity in experimental insulin resistance models. / Wang, Jing; Shi, Zhe; Zou, Tao; Zou, Min Xu; Yang, Hui Xian; Zhang, Cai Ping; Xiang, De Biao; Lin, Li Mei; Liu, Hui Yu; Fang, Deyu; Liao, Duan Fang.

In: Biomedicine and Pharmacotherapy, Vol. 109, 01.01.2019, p. 1276-1286.

Research output: Contribution to journalArticle

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AU - Zhang, Cai Ping

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AU - Fang, Deyu

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AB - Type 2 diabetes mellitus (T2DM) is a chronic degenerative endocrine and metabolic disease with high mortality and morbidity, yet lacks effective therapeutics. We recently generated a novel fusion peptide INSR-IgG4Fc, Yiminsu (YMS), to facilitate the high-affinity binding and transportation of insulin. Thus, the aim of the present study was to determine whether the novel recombinant peptide, YMS, could contribute to restoring insulin sensitivity and glycaemic control in insulin resistance models and revealing its underlying mechanism. Palmitic acid (PA)-treated LO2 cells and high fat diet (HFD)-fed mice were treated with YMS. Therapeutic effects of YMS were measured using Western blotting, ELISA, qPCR, Histology and transmission electron microscopy. We observed that YMS treatment effectively improved insulin signaling in PA-treated LO2 cells and HFD-fed mice. Notably, YMS could significantly reduce serum levels of glucose, triglycerides, fatty acids and cholesterol without affecting the serum insulin levels. Moreover, our data demonstrated that YMS could restore glucose and lipid homeostasis via facilitating insulin transportation and reactivating PI3K/Akt signaling in both PA-treated cells and liver, gastrocnemius and brown fat of HFD-fed mice. Additionally, we noticed that the therapeutic effects of YMS was similar as rosiglitazone, a well-recognized insulin sensitizer. Our findings suggested that YMS is a potentially candidate for pharmacotherapy for metabolic disorders associated with insulin resistance, particularly in T2DM.

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