Involvement of TGF-β and Autophagy Pathways in Pathogenesis of Diabetes: A Comprehensive Review on Biological and Pharmacological Insights

被引:38
作者
Heydarpour, Fatemeh [1 ]
Sajadimajd, Soraya [2 ]
Mirzarazi, Elahe [3 ]
Haratipour, Pouya [4 ,5 ]
Joshi, Tanuj [6 ]
Farzaei, Mohammad Hosein [7 ]
Khan, Haroon [8 ]
Echeverria, Javier [9 ]
机构
[1] Kermanshah Univ Med Sci, Hlth Technol Inst, Med Biol Res Ctr, Kermanshah, Iran
[2] Razi Univ, Dept Biol, Fac Sci, Kermanshah, Iran
[3] Univ Tehran, Inst Biochem & Biophys, Tehran, Iran
[4] Sharif Univ Technol, Dept Chem, Tehran, Iran
[5] Univ Sci Educ & Res Network USERN, PhytoPharmacol Interest Grp PPIG, Los Angeles, CA USA
[6] Kumaun Univ, Fac Technol, Dept Pharmaceut Sci, Naini Tal, India
[7] Kermanshah Univ Med Sci, Pharmaceut Sci Res Ctr, Kermanshah, Iran
[8] Abdul Wali Khan Univ, Dept Pharm, Mardan, Pakistan
[9] Univ Santiago Chile, Fac Quim & Biol, Dept Ciencias Ambiente, Santiago, Chile
关键词
diabetes; autophagy; TGF-beta; natural agents; systematic review; NF-KAPPA-B; ENDOPLASMIC-RETICULUM STRESS; EPITHELIAL-MESENCHYMAL TRANSITION; HEPATIC STELLATE CELLS; IMPROVES INSULIN SENSITIVITY; GAMMA-AMINOBUTYRIC-ACID; FATTY LIVER-DISEASE; PSIDIUM-GUA[!text type='JAVA']JAVA[!/text] L; GROWTH-FACTOR; OXIDATIVE STRESS;
D O I
10.3389/fphar.2020.498758
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Despite recent advancements in clinical drugs, diabetes treatment still needs further progress. As such, ongoing research has attempted to determine the precise molecular mechanisms of the disorder. Specifically, evidence supports that several signaling pathways play pivotal roles in the development of diabetes. However, the exact molecular mechanisms of diabetes still need to be explored. This study examines exciting new hallmarks for the strict involvement of autophagy and TGF-beta signaling pathways in the pathogenesis of diabetes and the design of novel therapeutic strategies. Dysregulated autophagy in pancreatic beta cells due to hyperglycemia, oxidative stress, and inflammation is associated with diabetes and accompanied by dysregulated autophagy in insulin target tissues and the progression of diabetic complications. Consequently, several therapeutic agents such as adiponectin, ezetimibe, GABA tea, geniposide, liraglutide, guava extract, and vitamin D were shown to inhibit diabetes and its complications through modulation of the autophagy pathway. Another pathway, TGF-beta signaling pathway, appears to play a part in the progression of diabetes, insulin resistance, and autoimmunity in both type 1 and 2 diabetes and complications in diabetes. Subsequently, drugs that target TGF-beta signaling, especially naturally derived ones such as resveratrol, puerarin, curcumin, hesperidin, and silymarin, as well as Propolis,Lycopus lucidus, andMomordica charantiaextracts, may become promising alternatives to current drugs in diabetes treatment. This review provides keen insights into novel therapeutic strategies for the medical care of diabetes.
引用
收藏
页数:21
相关论文
共 216 条
[1]   Exendin-4 Improves β-Cell Function in Autophagy-Deficient β-Cells [J].
Abe, Hiroko ;
Uchida, Toyoyoshi ;
Hara, Akemi ;
Mizukami, Hiroki ;
Komiya, Koji ;
Koike, Masato ;
Shigihara, Nayumi ;
Toyofuku, Yukiko ;
Ogihara, Takeshi ;
Uchiyama, Yasuo ;
Yagihashi, Soroku ;
Fujitani, Yoshio ;
Watada, Hirotaka .
ENDOCRINOLOGY, 2013, 154 (12) :4512-4524
[2]   EFFECT OF GREEN TEA RICH IN GAMMA-AMINOBUTYRIC-ACID ON BLOOD-PRESSURE OF DAHL SALT-SENSITIVE RATS [J].
ABE, Y ;
UMEMURA, S ;
SUGIMOTO, K ;
HIRAWA, N ;
KATO, Y ;
YOKOYAMA, N ;
YOKOYAMA, T ;
IWAI, J ;
ISHII, M .
AMERICAN JOURNAL OF HYPERTENSION, 1995, 8 (01) :74-79
[3]   Adiponectin improves insulin sensitivity via activation of autophagic flux [J].
Ahlstrom, Penny ;
Rai, Esther ;
Chakma, Suharto ;
Cho, Hee Ho ;
Rengasamy, Palanivel ;
Sweeney, Gary .
JOURNAL OF MOLECULAR ENDOCRINOLOGY, 2017, 59 (04) :339-350
[4]   Impaired TGF-β signaling and a defect in resolution of inflammation contribute to delayed wound healing in a female rat model of type 2 diabetes [J].
Al-Mulla, Fahd ;
Leibovich, Samuel J. ;
Francis, Issam M. ;
Bitar, Milad S. .
MOLECULAR BIOSYSTEMS, 2011, 7 (11) :3006-3020
[5]   Niemann-Pick C1 like 1 protein is critical for intestinal cholesterol absorption [J].
Altmann, SW ;
Davis, HR ;
Zhu, LJ ;
Yao, XR ;
Hoos, LM ;
Tetzloff, G ;
Iyer, SPN ;
Maguire, M ;
Golovko, A ;
Zeng, M ;
Wang, LQ ;
Murgolo, N ;
Graziano, MP .
SCIENCE, 2004, 303 (5661) :1201-1204
[6]   Vitamin D improves the content of TGF-β and IGF-1 in intervertebral disc of diabetic rats [J].
An, Ji-long ;
Zhang, Wei ;
Zhang, Jian ;
Lian, Li-chao ;
Shen, Yong ;
Ding, Wen-yuan .
EXPERIMENTAL BIOLOGY AND MEDICINE, 2017, 242 (12) :1254-1261
[7]   Transforming growth factor-β promotes invasion in tumorigenic but not in nontumorigenic human prostatic epithelial cells [J].
Ao, Mingfang ;
Williams, Karin ;
Bhowmick, Neil A. ;
Hayward, Simon W. .
CANCER RESEARCH, 2006, 66 (16) :8007-8016
[8]   The Smads [J].
Liliana Attisano ;
Si Tuen Lee-Hoeflich .
Genome Biology, 2 (8)
[9]   Altered plasma levels of nerve growth factor and transforming growth factor-β2 in type-1 diabetes mellitus [J].
Azar, ST ;
Major, SC ;
Safieh-Garabedian, B .
BRAIN BEHAVIOR AND IMMUNITY, 1999, 13 (04) :361-366
[10]   Treatment of diabetic mice with undenatured whey protein accelerates the wound healing process by enhancing the expression of MIP-1α, MIP-2, KC, CX3CL1 and TGF-β in wounded tissue [J].
Badr, Gamal ;
Badr, Badr M. ;
Mahmoud, Mohamed H. ;
Mohany, Mohamed ;
Rabah, Danny M. ;
Garraud, Olivier .
BMC IMMUNOLOGY, 2012, 13