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Summary
Dietary proteins are believed to take part considerably in sustaining blood glucose ranges, however their contribution to endogenous glucose manufacturing (EGP) stays unclear. We investigated this query utilizing a number of secure isotopes. After in a single day fasting, eight wholesome volunteers obtained an intravenous infusion of [6,6-2H2]-glucose. Two hours later, they ingested 4 eggs containing 23 g of intrinsically, uniformly, and doubly [15N]-[13C]–labeled proteins. Fuel exchanges, expired CO2, blood, and urine have been collected over the 8 h following egg ingestion. The cumulative quantity of dietary amino acids (AAs) deaminated over this 8-h interval was 18.1 ± 3.5%, 17.5% of them being oxidized. The EGP remained secure for six h however fell thereafter, concomitantly with blood glucose ranges. Throughout the 8 h after egg ingestion, 50.4 ± 7.7 g of glucose was produced, however solely 3.9 ± 0.7 g originated from dietary AA. Our outcomes present that the full postprandial contribution of dietary AA to EGP was small in people habituated to a food regimen medium-rich in proteins, even after an in a single day quick and within the absence of carbohydrates from the meal. These findings query the respective roles of dietary proteins and endogenous sources in producing vital quantities of glucose with a purpose to preserve blood glucose ranges in wholesome topics.
RESEARCH DESIGN AND METHODS – “does protein turn into glucose”
RESULTS
DISCUSSION
The target of this examine was to find out the metabolic conversion of dietary AAs into power and glucose metabolism, utilizing multi-isotope strategies that included the uniform double labeling of dietary AAs and a peripheral infusion of deuterated glucose. After the ingestion of a lipid-protein meal (4 eggs), 18% of AAs have been deaminated, producing carbon skeletons that have been solely oxidized inside 8 h of the meal. EGP didn’t enhance after the meal however remained secure for six h after which fell. Of the 50 g glucose produced over the 8-h interval, 4 g originated from dietary AAs, indicating that below our experimental circumstances, dietary protein-derived AAs contributed to solely 8% of EGP.
The power of dietary proteins to generate carbon skeletons from deamination will depend on the supply of the protein and the ordinary protein consumption of the themes, as deamination losses starting from 18–30% have been seen in research utilizing the same methodology (8,9,23–25). Throughout the present examine, the losses obtained with egg proteins have been 18% of consumption, which is akin to that noticed after the ingestion of whole milk proteins, indicating an excellent retention in protein swimming pools. Apparently, we discovered that every one deaminated AAs have been oxidized inside 8 h of meal ingestion, whereas after 4 h, solely half of them have been getting used as an power substrate. This compliments our earlier suggestion that using carbon skeletons in power pathways was delayed after the deamination course of due to the saturation of carbon cycles and an absence of power storage by these substrates (11). Though the dietary AA oxidation was solely approximated due to the variable 13C enrichment amongst AAs, the end result at 4 h was very per that obtained in rats utilizing extrinsic tracers (11), suggesting that the error was marginal. The retention in tricarboxylic acid pool might have been a supply of underestimation, however this must be of restricted extent as a result of labeling on all carbons as a substitute of a singular place (26).
Beneath optimum gluconeogenic circumstances, the 8-h postprandial manufacturing of glucose was ∼50 g, and the typical flux of EGP ranged from ∼10 µmol · min · kg−1 earlier than meal ingestion to 7 µmol · min · kg−1 8 h after the meal, which is per different research carried out after the ingestion of meals with various compositions (27–29). Our outcomes additionally confirmed that the ingestion of 4 eggs didn’t induce a rise in EGP, as the extent remained fixed till 5 h after the meal, lowering considerably thereafter. Apparently, we noticed that this lower was concomitant with the autumn in circulating glucose ranges. Some research had beforehand targeted on EGP following the ingestion of an HP meal or the infusion of AAs. Two research in wholesome people confirmed that an alanine infusion induced a rise in gluconeogenesis from alanine however no change in EGP. This might be defined by both an inhibition of gluconeogenesis from different substrates (30) or a lower in glycogenolysis (31). Certainly, the stimulation of 1 pathway for glucose manufacturing could also be counteracted by a downregulation of different pathways with a purpose to preserve secure world manufacturing (27,32). It’s, nevertheless, essential to emphasise the truth that pancreatic hormones (insulin and glucagon) have been clamped at basal ranges in these two experiments, and this will need to have influenced the outcomes. Certainly, one other examine carried out in wholesome topics however with none management of the plasma hormone ranges demonstrated that an infusion of AA led to a twofold rise in EGP, along with a threefold enhance in gluconeogenesis (5). Our experimental design was totally different from that work as a result of we have been finding out the results of meal ingestion fairly than a peripheral and steady infusion of AAs. As for the results of ingesting an HP meal, one examine identified that the ingestion of fifty g meat proteins (with out carbohydrates) led to a slight however regular lower in EGP in topics with kind 2 diabetes (33). EGP is upregulated in diabetic sufferers, however this impairment is very marked when insulin secretion is stimulated (34–36). Thus, within the case of a carbohydrate-free meal, and regardless of a slight stimulation of insulin secretion, it’s seemingly that the EGP response will likely be related in wholesome and diabetic sufferers. In wholesome topics, Khan et al. (12) confirmed that ingesting ∼50 g protein from cottage cheese with a small amount of carbohydrates and lipids induced a rise in EGP throughout the first 3 h, adopted by a marked lower from 3 to five h. The outcomes have diverged amongst research, due to both the experimental circumstances (infusion vs. meal) or variations in topic standing (wholesome vs. diabetic) or concerning the composition of the meal (presence or absence of carbohydrates, quantity of proteins, and power provide).
The usage of intrinsically labeled egg proteins enabled a quantification of the contribution of dietary protein to this manufacturing, which to our data had by no means beforehand been decided. We confirmed that after a standard consumption of protein (20–25 g), the contribution of dietary protein to glucose manufacturing was small and didn’t exceed 10% of the full flux throughout the 8-h postprandial interval, contributing the manufacturing of 4 g glucose to 50 g of whole glucose manufacturing. As 18% of dietary AAs have been deaminated, this represented about 4 g AA, amongst which 43% have been gluconeogenic in each egg-white and egg-yolk proteins (37), leading to 1.7 g of AA that might contribute to glucose manufacturing. Contemplating that three carbons in every AA can be transferred to a glucose molecule, we are able to assume that 1 mol of AA would contribute to 1/2 mol glucose. Nevertheless, the dilution of dietary AA within the endogenous swimming pools leads to a low likelihood that two labeled AAs are included in the identical glucose molecule. If the three remaining carbons are provided by precursors aside from dietary AAs, 1.7 g of gluconeogenic AA may thus take part within the manufacturing of three g glucose, a theoretical worth that’s akin to our findings. This speculation that 1 mol of glucose incorporates solely three carbons from dietary AAs must be confirmed with an isotopomer evaluation, however this may require the administration of extremely enriched gluconeogenic AAs. To our data, the examine of Khan et al. (12) is just one to have assessed postprandial gluconeogenesis on account of dietary proteins in people. The outcomes identified that ∼10 g of glucose was produced from proteins throughout the 8 h after the meal, which is per our findings concerning the quantity of protein ingested (50 g). This strongly means that the participation of dietary protein to glucose manufacturing primarily will depend on the quantity of gluconeogenic AA accessible, within the context of a low-carbohydrate meal. Altogether, we conclude to the robustness of our end result, regardless of methodological limits, such because the heterogeneous 13C labeling of AA, the potential lack of carbons in tricarboxylic acid cycle, and the absence of entry to the precursor pool (i.e., intrahepatic AAs).
The truth that the contribution of dietary AAs was low doesn’t preclude any excessive participation of proteins throughout fasting. Gluconeogenesis price throughout fasting and after exhaustion of glycogen retailer has been proven to be increased in topics fed an HP than normal-protein food regimen (4), suggesting a stronger use of physique protein in glucose manufacturing throughout the catabolic section. In our examine, 31 g of protein was oxidized, whereas solely 4 g was of dietary origin. Postulating that 45% of endogenous AAs are gluconeogenic (primarily based on basal circulating AA profiles), ∼6–12 g of endogenous AAs may subsequently be used as glucose precursors, relying on the supply of the complementary three carbons within the molecule.
Along with AAs, different potential sources for glucose manufacturing included different exogenous (glycerol from dietary and physique fats) or endogenous (primarily residual hepatic glycogen shops but in addition lactate or glycerol) sources. Because the check meal contained no carbohydrate however 19 g lipids, the glycerol launched by the postprandial catabolism of those lipids is likely to be the precursor of EGP. Nevertheless, contemplating that egg lipids comprise 66% triglycerides and 33% phospholipids (38), 28 mmol of glycerol can be launched in the event that they have been absolutely catabolized, which is prone to have occurred since 26 g of lipids have been oxidized. This could produce 2.5 g of glucose. In consequence, one other endogenous supply have to be the most important supply of glucose precursors, and hepatic glycogen is an effective candidate as a result of the shops that stay after fasting in a single day are nonetheless vital in regular topics. Utilizing 13C nuclear magnetic resonance, it has been proven that liver glycogen concentrations reached 207 mmol/L with a liver quantity of 1.44 L in people fasted in a single day (39), akin to ∼70 g. Such glycogen shops might alone account for the whole 8-h postprandial endogenous manufacturing of glucose (50 g). It has been proven that after in a single day fasting, glucose manufacturing from gluconeogenesis was 1.2 mg · kg−1 · min−1, akin to 34 g glucose (40), a price that can also be per the predictions of the modeling examine carried out by König et al. (41). In our examine, a correlation evaluation between glucose flux and nutrient oxidation confirmed that protein and lipid oxidation weren’t correlated to EGP, in distinction to carbohydrate oxidation (R = 0.24; P = 0.04), thus supporting the speculation that glycogen was the principal contributor to glucose flux below our experimental circumstances. Fig. 7 depicts the potential precursors of glucose manufacturing primarily based on our outcomes and on the speculation for nonobserved values.
In conclusion, this examine highlighted the truth that a major proportion of the carbon skeletons launched from dietary AA deamination was transformed into glucose throughout the 8 h following the ingestion of a protein-lipid and carbohydrate-free meal. Within the context of a low-calorie meal, gluconeogenesis is prone to be maximal in contrast with carbohydrate-containing meals. Regardless of this, the contribution of dietary AAs to glucose was 8%, relying primarily on the supply of gluconeogenic AAs, whereas that of endogenous AAs might attain 20%. It’s seemingly that almost all of this manufacturing, ∼70%, was as a result of degradation of residual liver glycogen, which might be enough, even after an in a single day quick. We will thus suppose that the participation of dietary proteins will likely be negligible within the presence of carbohydrates within the meal. We offered the primary direct proof that below optimum gluconeogenic circumstances and in a practical dietary scenario, dietary proteins solely make a comparatively modest contribution to the upkeep of blood glucose ranges.
“does protein turn into glucose”