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New hepatic targets for glycaemic control in diabetes
Open accessAbstract
Type-2 diabetes is associated with impaired glucose clearance by the liver in the postprandial state, and with elevated glucose production in the post-absorptive state. New targets within the liver are currently being investigated for development of antihyperglycaemic drugs for type-2 diabetes. They include glucokinase, which catalyses the first step in glucose metabolism, the glucagon receptor, and enzymes of gluconeogenesis and/or glycogenolysis such as glucose 6-phosphatase, fructose 1,6-bisphosphatase and glycogen phosphorylase. Preclinical studies with candidate drugs on animal models or cell-based assays suggest that these targets have the potential for pharmacological glycaemic control. Data from clinical studies is awaited. Further work is required for better understanding of the implications of targeting these sites in terms of possible side-effects or tachyphylaxis. The advantage of combined targeting of two or more sites within the liver for minimizing side-effects and tachyphylaxis caused by single-site targeting is discussed.
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“serum from type 2 diabetic patients treated with glargine activates insulin receptors A and B similarly to NPH insulin and does not increase signalling through the IGF-1 receptor128.”
From Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future (2014) · cites this paper as [128]
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Metadata
- Authors
- Agius, L.
- Affiliations
- Newcastle University (GB)
- Corresponding author
- Agius, Loranne
- ORCID
- Agius, Loranne
- Venue
- Best Practice & Research Clinical Endocrinology & Metabolism
- Publisher
- Elsevier BV
- Published
- 2007-12
- Volume
- 21
- Issue
- 4
- Pages
- 587-605
- ISSN
- 1521-690X (ISSN-L)
- OpenAlex
- W2132179056
- Cited by
- 155
- References
- 107
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 11 · 2019: 2 · 2018: 10 · 2017: 10 · 2016: 10 · 2015: 13 · 2014: 10 · 2013: 12 · 2012: 16
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Best Practice & Research Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Keywords
- type 2 diabetes, hepatic glucose metabolism, antidiabetic drugs, glucokinase, glucagon receptor, gluconeogenesis, glycogenolysis, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glycogen phosphorylase, tachyphylaxis, adverse drug reactions
- MeSH terms
- Animals, Binding Sites, Blood Glucose, Diabetes Mellitus, Type 2, Enzyme Inhibitors, Glucagon, Glucokinase, Gluconeogenesis, Glucose-6-Phosphatase, Fructose-Bisphosphatase, Humans, Hypoglycemic Agents, Liver, Glycogen Phosphorylase
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