Effects of soy protein and isoflavones on insulin resistance and adiponectin in male monkeys

Abstract

Isoflavones may influence insulin action by means of their well-known receptor-mediated estrogenic activity. However, isoflavones also bind to peroxisome proliferator-activated receptors (PPARs) that are strongly associated with insulin action. Soy protein with its isoflavones has previously been shown to improve glycemic control in diabetic postmenopausal women and to improve insulin sensitivity in ovariectomized monkeys. The purpose of the current report was to extend our studies of dietary soy protein to male monkeys and determine effects of the soy isoflavones on insulin resistance. Two studies are reported here. Study one involved 91 male monkeys consuming 3 diets differing only by the source of protein (casein-lactalbumin, soy protein with a low isoflavone concentration, or soy protein with a high isoflavone concentration). Intravenous glucose tolerance tests were done, and plasma adiponectin and lipoprotein concentrations were determined after 25 months of study. Samples of visceral fat were obtained at 31 months for assessment of adiponectin and PPARgamma expression. The second study involved 8 monkeys in a Latin-square design that compared the effects of diets with casein/lactalbumin, soy protein with a high isoflavone concentration, or soy protein that was alcohol-washed to deplete the isoflavones. After 8 weeks of treatment, insulin sensitivity and plasma lipoproteins were assessed. At 10 weeks, a biopsy of the skeletal muscle was performed for determination of insulin receptor, PPARalpha, and PPARgamma content. The major findings were that consumption of isoflavone-containing soy protein dose-dependently increased insulin responses to the glucose challenge and decreased plasma adiponectin, whereas isoflavone-depleted soy protein decreased body weight and had no effect on plasma adiponectin concentrations. Muscle PPARalpha and gamma expression was also increased with the isoflavone-depleted soy relative to either casein or soy protein containing the isoflavones. Further studies are needed to determine the mechanisms involved in these effects of a high-soy isoflavone diet and to optimize dietary isoflavone content for maximal health benefits in male subjects.

Figure 1

Glucose (top) and insulin (bottom) responses to an intravenous glucose tolerance test for monkeys consuming casein, soy protein with low isoflavone dose (Low Iso Soy) and high isoflavone dose (High Iso Soy). There were no changes in glucose response but a dose-dependent increase in insulin responses was found with isoflavone intake (ANOVA, p < 0.05). The treatment differences was due to High Iso Soy compared to Casein (P=0.03) and an intermediate response with Low Iso Soy compared to Casein (p=0.11).

Figure 2

Changes in insulin resistance (as determined by insulin/glucose areas under the curve (AUC) following a glucose challenge (as depicted in Fig1) and plasma adiponectin concentrations with monkeys consuming casein, soy protein with low isoflavone dose (Low Iso Soy) and high isoflavone dose (High Iso Soy). Adiponectin was significantly less in Low Iso compared to Casein (p = 0.02) with a similar trend for Hi Iso compared to Casein (p=0.08).

Figure 3

Change in body weight in monkeys with consumption of casein, soy protein alcohol washed to deplete isoflavones (SOY −), and soy protein with its isoflavones intact (SOY+) over a 10 week period using a Latin-square design. Body weights decreased (p<0.05) with consumption of SOY − compared to SOY+.

Figure 4

PPARγ and PPARα expression in skeletal muscle of monkeys with consumption of casein, soy protein alcohol-washed to deplete isoflavones (SOY−), and soy protein with its isoflavones intact (SOY+) after a 10 week period using a Latin-square design. Expression is significantly greater (p<0.05) for SOY− compared to casein.