A reduced carbohydrate, increased protein diet stabilizes glycemic control and minimizes adipose tissue glucose disposal in rats

The dietary reference intakes (DRIs) established an acceptable macronutrient distribution range (AMDR); however, few studies have evaluated differences in metabolic regulations across the DRI range. This study examined differences in glycemic regulations associated with specific ratios of carbohydrate and protein. Male rats (∼200 g) were fed either a high-carbohydrate diet (CHO group: 60% of energy as carbohydrates, 12% protein, 28% fat) or a reduced-carbohydrate diet [PRO (protein) group: 42% carbohydrates, 30% protein, 28% fat]. Rats consumed 3 meals/d with energy distributed as 16, 42, and 42%. On d 25, blood and tissues were obtained after 12 h of food deprivation and at 30 and 90 min after the first meal. Before the meal, the CHO group had lower plasma glucose and insulin, reduced liver glycogen, lower expression of hepatic phosphoenolpyruvate carboxylase (PEPCK), and increased fatty acid synthase (FAS) in adipose tissue. After the meal, the CHO group had greater increases in plasma glucose and insulin, producing increased skeletal muscle phosphatidylinositol 3-kinase (PI3-kinase) activity, glucose uptake, and glycogen content, and increased adipose PI3-kinase activity, glucose uptake, and FAS. In contrast, the PRO group had limited postprandial changes in plasma glucose and insulin with reduced muscle PI3-kinase activity and glucose uptake, and no postprandial changes in adipose PI3-kinase activity or FAS. This study demonstrates that changes in carbohydrate and protein intakes within the AMDR produce fundamental shifts in glycemic regulation from high-CHO diets that require insulin-mediated peripheral glucose disposal to high-PRO diets that increase hepatic regulation of glucose appearance into the blood.