A Reduced Carbohydrate, Increased Protein Diet Stabilizes Glycemic Control and Minimizes Adipose Tissue Glucose Disposal in Rats

Abstract

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 ( approximately 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.

Liver glyconeogenesis: a pathway to cope with postprandial amino acid excess in high-protein fed rats?

“…This pathway could participate in coping with amino acid excess in high-protein fed rats. In HP rats, the fed state was characterized by high hepatic glycogen levels, equivalent to those found in NP fed rats, in agreement with the findings of other studies (3,45,52). Moreover, we found that glucose release from isolated hepatocytes is very low and is not different between NP-and HP-fed rats.…”

“…Previous studies had reported a postprandial secretion of both insulin and glucagon in rats fed a HP diet (3,18). In that context, the respective influence of amino acids and insulin on glucagoninduced PEPCK and G6PC1 gene expression was investigated in vitro in primary cultures of isolated hepatocytes with constant concentration of glucose (5.5 mM).…”

“…High-protein feeding induced both insulin and glucagon secretion in the fed state, associated with the repletion of glycogen stores (3,45,52), whereas excess dietary amino acids are metabolized within tissues and the derived nitrogen released into the circulation in the form of glutamine, alanine, serine, and glycine (28,56). These amino acids are subsequently taken up by the liver, and the nitrogen is converted to urea and glutamine (12,28), the bulk of their carbon skeleton being converted to glucose through hepatic gluconeogenesis (8,29,37,51).…”

Obesity-related elevations in plasma leucine are associated with alterations in enzymes involved in branched-chain amino acid metabolism

“…Although the plasma levels of other amino acids may also change in obesity, the rises in the BCAAs are of particular interest because they appear to have unique obesity-related effects. Indeed, it has been posited that BCAAs may be responsible for some of the beneficial effects of high-protein diets, improving body weight control and adiposity (1,9,18,29,30,39). Similarly, BCAAs improve muscle glucose uptake, whole body glucose metabolism, and oxidation (7,8,43).…”

Glucagon acts in a dominant manner to repress insulin-induced mammalian target of rapamycin complex 1 signaling in perfused rat liver

“…Plasma insulin levels also increase in response to consumption of a high-protein meal, although the magnitude of the response is less compared with carbohydrate alone (2,3,16,30). However, in contrast to a high-carbohydrate meal, plasma glucagon levels increase rather than decrease in response to a high-protein meal (2,3,16,30). Based on the results of the present study, it might therefore be expected that mTORC1 signaling would be repressed in the liver after consumption of a high-protein meal.…”