Cited by 171Diabetes Treatment and ManagementMetabolism, Diabetes, and CancerPancreatic function and diabetes

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New hepatic targets for glycaemic control in diabetes

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Agius, Loranne·2007·Best Practice & Research Clinical Endocrinology & Metabolism

DOI 10.1016/j.beem.2007.09.001

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Abstract

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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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)
DOI: 10.1016/j.beem.2007.09.001
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
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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New hepatic targets for glycaemic control in diabetes

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