PMID- 34120289
OWN - NLM
STAT- MEDLINE
DCOM- 20220314
LR  - 20220314
IS  - 1573-2606 (Electronic)
IS  - 1389-9155 (Linking)
VI  - 22
IP  - 4
DP  - 2021 Dec
TI  - Beta-klotho in type 2 diabetes mellitus: From pathophysiology to therapeutic 
      strategies.
PG  - 1091-1109
LID - 10.1007/s11154-021-09661-1 [doi]
AB  - Type 2 diabetes mellitus (T2DM) has become a global health problem with no cure. 
      Despite lifestyle modifications and various pharmaceutical options, the 
      achievement of stable and durable glucose control along with effective prevention 
      of T2DM-related cardiovascular complications remains a challenging task in 
      clinical management. With its selective high abundance in metabolic tissues 
      (adipose tissue, liver, and pancreas), beta-Klotho is the essential component of 
      fibroblast growth factor (FGF) receptor complexes. It is essential for 
      high-affinity binding of endocrine FGF19 and FGF21 to evoke the signaling cascade 
      actively involved in homeostatic maintenance of glucose metabolism and energy 
      expenditure. In this Review, we discuss the biological function of beta-Klotho in 
      the regulation of glucose metabolism and offer mechanistic insights into its 
      involvement in the pathophysiology of T2DM. We review our current understanding 
      of the endocrine axis comprised of beta-Klotho and FGFs (FGF19 and FGF21) and its 
      regulatory effects on glucose metabolism under physiological and T2DM conditions. 
      We also highlight advances in the development and preclinical validation of 
      pharmacological compounds that target beta-Klotho and/or the beta-Klotho-FGFRs complex 
      for the treatment of T2DM. Given the remarkable advances in this field, we also 
      discuss outstanding research questions and the many challenges in the clinical 
      development of beta-Klotho-based therapies.
CI  - (c) 2021. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Hua, Shuang
AU  - Hua S
AD  - Key Laboratory of Glucolipid Metabolic Diseases of The Ministry of Education, 
      Guangzhou, China.
AD  - Guangdong Metabolic Disease Research Center of Integrated Chinese and Western 
      Medicine, Guangdong Pharmaceutical University, Guangzhou, China.
FAU - Liu, Qianying
AU  - Liu Q
AD  - Key Laboratory of Glucolipid Metabolic Diseases of The Ministry of Education, 
      Guangzhou, China.
AD  - Guangdong Metabolic Disease Research Center of Integrated Chinese and Western 
      Medicine, Guangdong Pharmaceutical University, Guangzhou, China.
FAU - Li, Jufei
AU  - Li J
AD  - Key Laboratory of Glucolipid Metabolic Diseases of The Ministry of Education, 
      Guangzhou, China.
AD  - Guangdong Metabolic Disease Research Center of Integrated Chinese and Western 
      Medicine, Guangdong Pharmaceutical University, Guangzhou, China.
FAU - Fan, Mengqi
AU  - Fan M
AD  - Key Laboratory of Glucolipid Metabolic Diseases of The Ministry of Education, 
      Guangzhou, China.
AD  - Guangdong Metabolic Disease Research Center of Integrated Chinese and Western 
      Medicine, Guangdong Pharmaceutical University, Guangzhou, China.
FAU - Yan, Kaixuan
AU  - Yan K
AD  - Key Laboratory of Glucolipid Metabolic Diseases of The Ministry of Education, 
      Guangzhou, China.
AD  - Guangdong Metabolic Disease Research Center of Integrated Chinese and Western 
      Medicine, Guangdong Pharmaceutical University, Guangzhou, China.
FAU - Ye, Dewei
AU  - Ye D
AUID- ORCID: 0000-0003-1295-3063
AD  - Key Laboratory of Glucolipid Metabolic Diseases of The Ministry of Education, 
      Guangzhou, China. deweiye@gdpu.edu.cn.
AD  - Guangdong Metabolic Disease Research Center of Integrated Chinese and Western 
      Medicine, Guangdong Pharmaceutical University, Guangzhou, China. 
      deweiye@gdpu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20210613
PL  - Germany
TA  - Rev Endocr Metab Disord
JT  - Reviews in endocrine & metabolic disorders
JID - 100940588
RN  - 62031-54-3 (Fibroblast Growth Factors)
SB  - IM
MH  - Adipose Tissue/metabolism
MH  - *Diabetes Mellitus, Type 2/drug therapy/metabolism
MH  - Fibroblast Growth Factors/metabolism
MH  - Homeostasis
MH  - Humans
MH  - Liver/metabolism
MH  - Signal Transduction/physiology
OTO - NOTNLM
OT  - Diabetes
OT  - FGF21
OT  - Hyperglycemia
OT  - Insulin resistance
OT  - Klotho
EDAT- 2021/06/14 06:00
MHDA- 2022/03/15 06:00
CRDT- 2021/06/13 21:06
PHST- 2021/05/28 00:00 [accepted]
PHST- 2021/06/14 06:00 [pubmed]
PHST- 2022/03/15 06:00 [medline]
PHST- 2021/06/13 21:06 [entrez]
AID - 10.1007/s11154-021-09661-1 [pii]
AID - 10.1007/s11154-021-09661-1 [doi]
PST - ppublish
SO  - Rev Endocr Metab Disord. 2021 Dec;22(4):1091-1109. doi: 
      10.1007/s11154-021-09661-1. Epub 2021 Jun 13.