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New hepatic targets for glycaemic control in diabetes

Lookup NU author(s): Professor Loranne Agius

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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. © 2007 Elsevier Ltd. All rights reserved.

Publication metadata

Author(s): Agius L

Publication type: Review

Publication status: Published

Journal: Best Practice and Research: Clinical Endocrinology and Metabolism

Year: 2007

Volume: 21

Issue: 4

Pages: 587-605

Print publication date: 01/12/2007

ISSN (print): 1521-690X

ISSN (electronic): 1532-1908

URL: http://dx.doi.org/10.1016/j.beem.2007.09.001

DOI: 10.1016/j.beem.2007.09.001

PubMed id: 18054737

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