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2005, Number 1

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Rev Endocrinol Nutr 2005; 13 (1)

Pharmacogenomic application in actions of the hepatocyte related with the glucose metabolism (2nd article)

Bastarrachea RA, Rosas-Guzmán J, Kent J, Cai G, Téllez-Mendoza J, Comuzzie AG

Language: Spanish
References: 41
Page: 24-32
PDF size: 110.23 Kb.


ABSTRACT

Current drug treatments for type 2 diabetes include stimulation of insulin secretion, inhibition of endogenous glucose production and enhancement of insulin sensitivity. However, more efficacious therapies are needed. Recent molecular developments in understanding the interaction between carbohydrate and fatty acid metabolism may guide us to novel pharmacological targets in this area. Promising biological targets are also emerging such as non-peptide glucagon-receptor antagonists, and several hepatic enzyme targets that regulate rate-controlling steps in the gluconeogenic or glycogenolytic pathways. Genomic examination of the insulin-glucose axis has provided a wealth of information about changes in gene expression in diabesity. cDNA microarrays and oligonucleotide arrays facilitate the simultaneous quantitation of thousands of mRNAs and provide a comprehensive assessment of expression levels. These techniques examine the level of mRNA gene expression in tissues from lean and obese animal models and humans. The observed changes in gene expression indicate the molecular transition from the lean to obese state and reflect the cell biology in the pathogenesis of diabesity. The comparison of several types of tissues (muscle, liver, adipose tissue) among lean and obese study subjects will allow us to discover patterns of differential gene expression when a drug is administered. With these new opportunities for drug discovery, the prospects are optimistic for development of therapies to effectively manage diabetes and prevent its long term complications.


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