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J. Biol. Chem., Vol. 282, Issue 28, 20657-20666, July 13, 2007

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Pancreatic Insulin Secretion in Rats Fed a Soy Protein High Fat Diet Depends on the Interaction between the Amino Acid Pattern and Isoflavones^*

Lilia Noriega-López, Armando R. Tovar, Marcela Gonzalez-Granillo^¶, Rogelio Hernández-Pando^||, Bruno Escalante, Patricio Santillán-Doherty^**, and Nimbe Torres¹

From the Depto. de Fisiología de la Nutrición, ^**Depto. de Cirugía Experimental, and ^||Depto. Patología Experimental Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", D.F. 14000, the Depto. de Biomedicina Molecular, CINVESTAV, D.F. 07360, and the ^¶Universidad Iberoamericana, México, D.F. 01219, México

Obesity is frequently associated with the consumption of high carbohydrate/fat diets leading to hyperinsulinemia. We have demonstrated that soy protein (SP) reduces hyperinsulinemia, but it is unclear by which mechanism. Thus, the purpose of the present work was to establish whether SP stimulates insulin secretion to a lower extent and/or reduces insulin resistance, and to understand its molecular mechanism of action in pancreatic islets of rats with diet-induced obesity. Long-term consumption of SP in a high fat (HF) diet significantly decreased serum glucose, free fatty acids, leptin, and the insulin:glucagon ratio compared with animals fed a casein HF diet. Hyperglycemic clamps indicated that SP stimulated insulin secretion to a lower extent despite HF consumption. Furthermore, there was lower pancreatic islet area and insulin, SREBP-1, PPAR, and GLUT-2 mRNA abundance in comparison with rats fed the casein HF diet. Euglycemic-hyperinsulinemic clamps showed that the SP diet prevented insulin resistance despite consumption of a HF diet. Incubation of pancreatic islets with isoflavones reduced insulin secretion and expression of PPAR. Addition of amino acids resembling the plasma concentration of rats fed casein stimulated insulin secretion; a response that was reduced by the presence of isoflavones, whereas the amino acid pattern resembling the plasma concentration of rats fed SP barely stimulated insulin release. Infusion of isoflavones during the hyperglycemic clamps did not stimulate insulin secretion. Therefore, isoflavones as well as the amino acid pattern seen after SP consumption stimulated insulin secretion to a lower extent, decreasing PPAR, GLUT-2, and SREBP-1 expression, and ameliorating hyperinsulinemia observed during obesity.

Received for publication, February 5, 2007 , and in revised form, May 9, 2007.

^* This work was supported by the Consejo Nacional de Ciencia y Tecnología (CONACYT) Grant 46135-M (to N. T.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición, Vasco de Quiroga No 15, Tlalpan, México, D, F., 14000, México. Tel.: 525-6553038; Fax: 525-6551076; E-mail: nimbet{at}quetzal.innsz.mx.

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