Objetivos moleculares para diseñar nuevos fármacos para el tratamiento de la diabetes tipo 2 y la obesidad

Translated title of the contribution: Molecular targets for new drug discovery to treat type 2 diabetes and obesity

Raúl A. Bastarrachea, Julio C. Montero, Víctor Saavedra-Gajardo, Ricardo Cerda-Flores, Anselmo Machado-Domínguez, Anthony G. Comuzzie

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations

Abstract

Current strategies to treat type 2 diabetes (DMT2) include reducing insulin resistance using glitazones, supplementing with exogenous insulin, increasing endogenous insulin production with sulfonylureas and meglitinides, reducing hepatic glucose production through biguanides, and limiting postprandial glucose absorption with alphaglucosidase inhibitors. In all of these areas, new generations of molecules with improved efficacy and safety profiles, are being investigated. Promising biological targets are rapidly emerging such as the role of lipotoxicity as a cause of glucometabolic insulin resistance, leading to a host of new molecular drug targets such as AMP-activated protein kinase (AMPK) activators, recombinant adiponectin derivatives, and fatty acid synthase (FAS) inhibitors. Insulin action can be enhanced in muscle, liver and fat, with small-molecule activators of the insulin receptor or inhibitors of protein tyrosine phosphatase (PTP)-1B. Defective glucosestimulated insulin secretion by pancreatic β-cells could be alleviated with recombinant glucagon-like peptide (GLP-1) or agonists to the GLP-1 receptor. This review presents a new approach for obesity and DMT2 drug discovery through pharmacogenomics. Several compounds have already been validated through genetic engineering in animal models or the preliminary use of therapeutic compounds in humans.

Translated title of the contributionMolecular targets for new drug discovery to treat type 2 diabetes and obesity
Original languageSpanish
Pages (from-to)107-117
Number of pages11
JournalRevista Medica de Chile
Volume136
Issue number1
StatePublished - Jan 2008
Externally publishedYes

Keywords

  • Diabetes, type 2
  • Obesity
  • Pharmacogenetics

ASJC Scopus subject areas

  • Medicine(all)

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