PMID- 32162273
OWN - NLM
STAT- MEDLINE
DCOM- 20201207
LR  - 20201214
IS  - 1179-1950 (Electronic)
IS  - 0012-6667 (Linking)
VI  - 80
IP  - 5
DP  - 2020 Apr
TI  - Glucokinase Activators for Type 2 Diabetes: Challenges and Future Developments.
PG  - 467-475
LID - 10.1007/s40265-020-01278-z [doi]
AB  - Increased hepatic glucose output, the primary liver dysregulation associated with 
      Type 2 diabetes mellitus (T2DM), is not directly or effectively targeted by the 
      currently available classes of glucose-lowering medications except metformin. 
      This unmet need might be addressed through activation of a specific enzyme-member 
      of the hexokinase family, namely glucokinase (GK). GK serves as a 
      "glucose-sensor" or "glucose receptor" in pancreatic cells, eliciting 
      glucose-stimulated insulin secretion, and as glucose "gate-keeper" in 
      hepatocytes, promoting hepatic glucose uptake and glycogen synthesis and storage. 
      GK activation by small molecules present an alternative approach to 
      restore/improve glycaemic control in patients with T2DM. GK activators (GKAs) may 
      increase insulin secretion from the pancreas and promote glycogen synthesis in 
      the liver, and hence reduce hepatic glucose output. Despite several setbacks in 
      their development, interest in the GKA class has been renewed, particularly since 
      the introduction of a novel, dual-acting full GKA, dorzagliatin, and a novel 
      hepatoselective molecule, TTP399. In this article we provide an overview of the 
      role, efficacy, safety and future developments of GKAs in the management of T2DM.
FAU - Toulis, Konstantinos A
AU  - Toulis KA
AUID- ORCID: 0000-0002-2044-4253
AD  - Institute of Applied Health Research, University of Birmingham, Birmingham, UK.
AD  - Department of Endocrinology, 424 General Military Hospital, Thessaloniki, Greece.
FAU - Nirantharakumar, Krishnarajah
AU  - Nirantharakumar K
AD  - Institute of Applied Health Research, University of Birmingham, Birmingham, UK.
FAU - Pourzitaki, Chrysa
AU  - Pourzitaki C
AD  - Department of Clinical Pharmacology, Faculty of Medicine, School of Health 
      Sciences, Aristotle University of Thessaloniki, 541 24, Thessaloniki, Greece.
FAU - Barnett, Anthony H
AU  - Barnett AH
AD  - Institute of Metabolism and Systems Research, University of Birmingham, 
      Birmingham, UK.
AD  - Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, 
      Birmingham, UK.
AD  - Department of Diabetes and Endocrinology, University Hospitals NHS Foundation 
      Trust, Birmingham, UK.
FAU - Tahrani, Abd A
AU  - Tahrani AA
AD  - Institute of Metabolism and Systems Research, University of Birmingham, 
      Birmingham, UK. A.A.Tahrani@bham.ac.uk.
AD  - Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, 
      Birmingham, UK. A.A.Tahrani@bham.ac.uk.
AD  - Department of Diabetes and Endocrinology, University Hospitals NHS Foundation 
      Trust, Birmingham, UK. A.A.Tahrani@bham.ac.uk.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - New Zealand
TA  - Drugs
JT  - Drugs
JID - 7600076
RN  - 0 (Organic Chemicals)
RN  - 0 (Pyrazoles)
RN  - 0 (TTP399)
RN  - EC 2.7.1.2 (Glucokinase)
RN  - X59W6980E8 (Dorzagliatin)
SB  - IM
MH  - Animals
MH  - Diabetes Mellitus, Type 2/*metabolism
MH  - Glucokinase/*metabolism
MH  - Humans
MH  - Organic Chemicals/pharmacology
MH  - Pyrazoles/pharmacology
EDAT- 2020/03/13 06:00
MHDA- 2020/12/15 06:00
CRDT- 2020/03/13 06:00
PHST- 2020/03/13 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PHST- 2020/03/13 06:00 [entrez]
AID - 10.1007/s40265-020-01278-z [pii]
AID - 10.1007/s40265-020-01278-z [doi]
PST - ppublish
SO  - Drugs. 2020 Apr;80(5):467-475. doi: 10.1007/s40265-020-01278-z.