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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Prospects for Pharmacologic Inhibition of Hepatic Glucose Production

Author(s): R. Kurukulasuriya, J. T. Link, D. J. Madar, Z. Pei, J. J. Rohde, S. J. Richards, A. J. Souers and B. G. Szczepankiewicz

Volume 10, Issue 2, 2003

Page: [99 - 121] Pages: 23

DOI: 10.2174/0929867033368547

Price: $65


Type 2 diabetes is a widespread disease where effective pharmacologic therapies can have a profound beneficial public health impact. Increased hepatic glucose production (HGP) is observed in diabetics and its moderation by currently available agents provides therapeutic benefits. This review describes the challenges associated with the discovery of small molecules that inhibit HGP. Gluconeogenesis, glycogenolysis, liver architecture, and hepatocyte composition are described to provide background information on hepatic function. Current methods of target validation for drug discovery, HGP measurement, diabetes animal models, as well as current drug therapies are covered. In the accompanying review article the new drug targets being probed to produce the next generation of therapies are described. Significant pharmaceutical and academic efforts to pharmacologically inhibit HGP has the opportunity to provide new therapeutics for type 2 diabetics.

Keywords: hepatic glucose production, diabetes, hyperglycemia, metformin, gluconeogenesis, glycogenolysis, liver, liver targeting

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