Mutations in the liver glycogen synthase gene in children with hypoglycemia due to glycogen storage disease type 0.

Glycogen storage disease type 0 (GSD-0) is a rare form of fasting hypoglycemia presenting in infancy or early childhood and accompanied by high blood ketones and low alanine and lactate concentrations. Although feeding relieves symptoms, it often results in postprandial hyperglycemia and hyperlactatemia. The glycogen synthase (GS) activity has been low or immeasurable in liver biopsies, whereas the liver glycogen content has been only moderately decreased. To investigate whether mutations in the liver GS gene (GYS2) on chromosome 12p12.2 were involved in GSD-0, we determined the exon-intron structure of the GYS2 gene and examined nine affected children from five families for linkage of GSD-0 to the GYS2 gene. Mutation screening of the 16 GYS2 exons was done by single-strand conformational polymorphism (SSCP) and direct sequencing. Liver GS deficiency was diagnosed from liver biopsies (GS activity and glycogen content). GS activity in the liver of the affected children was extremely low or nil, resulting in subnormal glycogen content. After suggestive linkage to the GYS2 gene had been established (LOD score = 2.9; P < 0.01), mutation screening revealed several different mutations in these families, including a premature stop codon in exon 5 (Arg246X), a 5'-donor splice site mutation in intron 6 (G+1T--> CT), and missense mutations Asn39Ser, Ala339Pro, His446Asp, Pro479Gln, Ser483Pro, and Met491Arg. Seven of the affected children carried mutations on both alleles. The mutations could not be found in 200 healthy persons. Expression of the mutated enzymes in COS7 cells indicated severely impaired GS activity. In conclusion, the results demonstrate that GSD-0 is caused by different mutations in the GYS2 gene.

Oral protein hydrolysate causes liver glycogen depletion in fasted rats pretreated with glucose.

Studies in rats indicated that the major physiologic stimulus for synthesis of liver glycogen is a rise in the portal glucose concentration after ingestion of a meal. Conversely, glycogen degradation in the liver is stimulated by a rise in portal glucagon concentration. In humans, ingestion of carbohydrate lowers the concentration of circulating glucagon, whereas protein stimulates an increase in peripheral glucagon concentration. Little is known about the effects of these nutrients on glucagon concentrations in the rat. Therefore, we studied the effects of oral protein administration to 24-h-fasted rats pretreated with glucose for 2 h to test the effect of two potent but potentially opposite signals for glycogen metabolism. An increase in liver glycogen concentration was observed in fasted rats given oral glucose, as expected. Removal of glucose by the liver could not account for the glycogen synthesized, indicating that most glycogen formed was derived from gluconeogenesis. In addition, the apparent intracellular and extracellular glucose concentrations were not in equilibrium. A small amount of glucose may have been taken up against a concentration gradient. The portal glucagon was not significantly decreased. Oral protein administration to the rats pretreated with glucose resulted in a rapid and dramatic decrease in liver glycogen concentration. This was associated with an increase in the portal glucagon concentration, no change in insulin concentration, a slight increase in liver cAMP concentration, an increase in the active form of phosphorylase, and a decrease in the active form of synthase. Glycogenolysis could account for the glucose released into the circulation from the liver after protein administration.

Quantitative importance of dietary constituents other than glucose as insulin secretagogues in type II diabetes.

In seven type II (non-insulin-dependent) diabetic patients, given either 50 g glucose or a mixed meal potentially containing 61 g glucose as starch and sucrose, the postmeal plasma glucose area integrated over 4 h was less after the mixed meal. The insulin area was considerably greater (2.1-fold). The greater increase in insulin could be explained largely, but not entirely, by the protein and fructose in the mixed meal (85%) which, in addition to glucose, are known insulin secretagogues. The residual unexplained increase may be due to a synergistic interaction of these secretagogues, an unidentified insulin secretagogue, or by a reduced insulin removal rate. These possibilities remain to be explored.

Sucrose and disease.

Data currently available indicate that high sucrose consumption does not contribute significantly to the prevalence of cardiovascular disease, diabetes mellitus, obesity, or micronutrient deficiency. It may contribute, however, to dental caries formation by cariogenic bacteria.

Factors affecting interpretation of postprandial glucose and insulin areas.

Recently there has been an increased interest in determining the circulating glucose concentration after the ingestion of various individual foods and mixed meals. The purpose of these determinations is to systematically rank foods with respect to their quantitative effect on postmeal glucose concentration. Potentially such data could be useful in designing a diet for individuals with diabetes. We believe this concept is good. However, several factors that may affect interpretation of the data used to develop this ranking need to be considered before the utility of this approach to dietary management can be assessed: 1) duration of time over which the data are collected and analyzed; 2) use of absolute versus incremental areas in the determinations; 3) inclusion or exclusion of negative areas if incremental areas are used; 4) differences in response to a given food in males compared with females; 5) severity of diabetes; 6) confounding effects of oral agents or insulin treatment; 7) reproducibility of data; 8) differences in collection of blood sample; 9) food composition, processing, and preparation; 10) the dose-response relationship to ingestion of a given carbohydrate; 11) the meal being studied, i.e., first, second, or third meal of the day; and 12) a possible effect of the composition of the previous meal, if the response is tested to any meal other than the first meal of the day.

Plasma glucose and insulin response to macronutrients in nondiabetic and NIDDM subjects.

Information on the metabolic response in people with non-insulin-dependent diabetes mellitus (NIDDM) to ingested individual macronutrients is limited. Available information is reviewed herein. The major absorbed products of carbohydrate-containing foods are glucose, fructose, and galactose. The quantitative effect of these on the plasma glucose and insulin response is different for each. In addition, available data indicate that the glucose and particularly the insulin response is different from that in nondiabetic people. The quantitative effect of dietary proteins and fats on the circulating glucose and insulin concentrations in nondiabetic and NIDDM subjects also has been reviewed. Neither has a significant effect on the glucose concentration. Protein stimulates insulin secretion, and this is relatively more prominent in people with NIDDM. A strong synergistic interaction with glucose on insulin secretion is present, but this is absent in nondiabetic people. Ingested fat does not independently stimulate insulin secretion. However, when ingested with carbohydrate, it may have a considerable effect on the plasma glucose and/or insulin response to that carbohydrate, and the responses are different in nondiabetic and NIDDM subjects. This is probably not due to altered carbohydrate absorption. Intestinal hormones undoubtedly are playing a large role in the insulin secretory response in all of these studies, but this remains to be completely elucidated. Overall, the data indicate that the metabolic response to various foods determined in people with NIDDM may be different than that in nondiabetic people. In our opinion, much more information is required before dietary recommendations for NIDDM subjects can be made based on solid scientific data.

Effect of added fat on the plasma glucose and insulin response to ingested potato given in various combinations as two meals in normal individuals.

OBJECTIVE: In normal subjects, ingestion of fat with potato in a morning meal resulted in a decrease in the glucose response. Therefore, we wished to determine whether a fat-induced decrease in blood glucose also would be observed after a second identical meal. In addition, we were interested in determining if fat ingestion with a morning meal would have an effect on the blood glucose and insulin responses to a second meal not containing fat. RESEARCH DESIGN AND METHODS: Nine healthy male subjects ingested two meals consisting of an amount of potato containing 50 g carbohydrate, either alone or with 50 g fat as butter. The meals were served in four combinations as follows: 1) potato for the first meal, potato for the second meal; 2) potato for the first meal, potato with fat for the second meal; 3) potato with fat for the first meal, potato for the second meal; and 4) potato with fat for the first meal, potato with fat for the second meal. Meals were ingested at 8:00 A.M. and noon. Plasma glucose and C-peptide, serum insulin, triglyceride, and free fatty acid (FFA) concentrations were determined over an 8-h period. The integrated area responses to the meals were quantified over the subsequent 4-h period using the fasting value or the noon value as baseline for the first and second meals, respectively. RESULTS: When the first meal contained potato only, the glucose area response to the second meal was significantly less when the second meal contained fat. However, fat ingestion had no effect on the glucose area response to the second meal when fat was present in the first meal. The insulin area responses to the first and second meals were similar after ingestion of potato or potato with fat. However, the insulin response to the second meal always was less than that to the first meal. The C-peptide area responses after ingestion of the second meal also were all higher than those after the first meal. The triglyceride area responses were slightly negative after ingestion of potato alone in the first meal. When fat was ingested, they were positive. When the first meal contained fat but the second meal did not, there was a rise in triglyceride concentration after the second meal as well as after the first meal. That is, a rise occurred without ingestion of fat with the second meal. If fat was present in the second meal the rise was even greater. The FFA area responses were similar to the triglyceride area responses. CONCLUSIONS: When fat was ingested with carbohydrate in either the first or second meal, the glucose area response was decreased. However, when both meals contained fat, a decrease in the glucose area response did not occur with the second meal. The glucose area responses all were greater after the second meal compared with those after the first meal, i.e., the opposite of a Staub-Traugott effect was observed. The insulin area responses to the first and second meals were similar whether fat was ingested or not.

Effect of added fat on plasma glucose and insulin response to ingested potato in individuals with NIDDM.

OBJECTIVE: In normal subjects, ingestion of butter with potato resulted in considerably lower blood glucose levels but similar or higher insulin concentrations compared with those observed in the same subjects after potato ingestion alone. We determined whether butter ingested with potato would result in a greater stimulation in insulin secretion than ingestion of potato alone in subjects with NIDDM. RESEARCH DESIGN AND METHODS: Seven male subjects with untreated NIDDM ingested 50 g CHO alone or 50 g CHO with 5, 15, 30, or 50 g fat as a breakfast meal. Fat was ingested in the form of butter, and CHO was given in the form of potato. Subjects received 50 g glucose on two separate occasions for comparative purposes. The subjects also were given only water and were studied over the same time period (water control). Plasma glucose, glucagon, alpha-amino nitrogen, nonesterified fatty acids, serum insulin, C-peptide, and triglyceride concentrations were determined over 5 h. The integrated area responses were quantified over the 5-h period using the water control as a baseline. RESULTS: The mean plasma glucose area response after ingestion of potato with or without the various amounts of butter were all similar and were 82% of that observed after ingestion of 50 g glucose. The mean insulin area response to potato alone was 532 pmol.h.L-1. The mean insulin area responses to potato plus 5,15,30, and 50 g of fat meals were 660,774,750, and 756 pmol.h.L-1, respectively. Thus, the mean insulin areas were all greater than for ingestion of potato alone, and a maximal response was observed with addition of 15 g fat (1.4-fold). The C-peptide data did not confirm an increase in insulin secretion. Overall the area responses after ingestion of meals containing fat were not different from the response to potato ingestion alone, although the responses were erratic. The glucagon area response was positive after ingestion of all fat containing meals except for that containing only 5 g fat, and there was a dose-response relationship. The plasma alpha-amino nitrogen and nonesterified fatty acid area responses were negative after potato ingestion and were not significantly different when fat was added. The serum triglyceride concentration increase was greater after the ingestion of butter with the potato as expected. CONCLUSIONS: In contrast to the results in normal subjects after ingestion of butter with potato, the glucose response was not smaller in subjects with NIDDM. The insulin response was greater. The insulin area response data indicated the presence of a dose-response relationship. Whether similar responses will be observed with other dietary fat and CHO sources remains to be determined.

Insulin and glucose responses to various starch-containing foods in type II diabetic subjects.

The circulating insulin and glucose responses in type II diabetic subjects were determined for 5 h after ingestion of various meals, each containing 50 g carbohydrate. The purpose of the study was to 1) systematically study the insulin response to several different high-starch foods, 2) determine whether this insulin response could be predicted by the glucose response, and 3) determine whether the glucose response could be predicted by the physical structure and digestibility of the ingested carbohydrate. Each subject served as his own control. Carbohydrate was given in the form of potatoes, bread, oatmeal, rice, lentils, kidney beans, cornflakes, high-amylose corn muffins, and low-amylose corn muffins. Bread, oatmeal, rice, lentils, kidney beans, and high-amylose corn muffins resulted in a significantly lower glucose area than 50 g glucose, and the glucose response generally could be predicted by the physical structure and the known digestibility of the ingested carbohydrate. The insulin rise was statistically significantly greater than would be predicted from the glucose response for oatmeal, lentils, kidney beans, and high-amylose corn muffins. Although not statistically significant, the mean was greater than predicted for every other food except potatoes when the insulin response to 50 g glucose was used as a standard. These results indicate that the insulin response cannot be predicted by the glucose response.

Effect of protein ingestion on the glucose and insulin response to a standardized oral glucose load.

Type II diabetic subjects were given 50 g protein, 50 g glucose, or 50 g glucose with 50 g protein as a single meal in random sequence. The plasma glucose and insulin response was determined over the subsequent 5 h. The plasma glucose area above the baseline following a glucose meal was reduced 34% when protein was given with the glucose. When protein was given alone, the glucose concentration remained stable for 2 h and then declined. The insulin area following glucose was only modestly greater than with a protein meal (97 +/- 35, 83 +/- 19 microU X h/ml, respectively). When glucose was given with protein, the mean insulin area was considerably greater than when glucose or protein was given alone (247 +/- 33 microU X h/ml). When various amounts of protein were given with 50 g glucose, the insulin area response was essentially first order. Subsequently, subjects were given 50 g glucose or 50 g glucose with 50 g protein as two meals 4 h apart in random sequence. The insulin areas were not significantly different for each meal but were higher when protein + glucose was given. After the second glucose meal the plasma glucose area was 33% less than after the first meal. Following the second glucose + protein meal the plasma glucose area was markedly reduced, being only 7% as large as after the first meal. These data indicate that protein given with glucose will increase insulin secretion and reduce the plasma glucose rise in at least some type II diabetic persons.

Stimulation of insulin secretion by fructose ingested with protein in people with untreated type 2 diabetes.

OBJECTIVE: Ingested protein provides substrate for gluconeogenesis and strongly stimulates insulin and glucagon secretion, but it has little effect on the glucose concentration in people with type 2 diabetes. Ingested fructose also is a substrate for gluconeogenesis, modestly stimulates insulin and glucagon secretion, and has little effect on the plasma glucose. Therefore we were interested in determining if ingestion of fructose along with protein would result in an additive, greater than additive, or less than additive effect on circulating insulin, glucagon, and glucose concentrations. RESEARCH DESIGN AND METHODS: Seven male subjects with untreated type 2 diabetes were fasted overnight and then were given either 25 g fructose, 25 g protein, 25 g fructose plus 25 g protein, or water only at 0800. Subjects also ingested 50 g glucose on two separate occasions. Plasma glucose, insulin, C-peptide, glucagon, alpha-amino nitrogen, urea nitrogen, nonesterified fatty acids, and triglyceride concentrations were determined over the subsequent 5 h. RESULTS: The glucose concentration was only modestly increased and the area responses were similar when protein, fructose, or the combination was ingested. Thus, the glucose response to the combination was less than additive. The insulin area response to protein was 2.5-fold greater than to fructose, and the response to the two nutrients was additive and quantitatively similar to the response to 50 g glucose. The glucagon area response was less than additive, i.e., there was an interaction between the protein and fructose that resulted in a smaller than expected response. CONCLUSIONS: When protein and fructose were ingested together, the insulin response was similar to that following ingestion of 50 g glucose. It also was as expected based on the response to the individual nutrients. In contrast, the glucose and glucagon responses were significantly less than expected. These data may be useful in dietary planning for subjects with type 2 diabetes.

Effects of dose of ingested glucose on plasma metabolite and hormone responses in type II diabetic subjects.

Ten untreated type II (non-insulin-dependent) diabetic subjects were given 15, 25, 35, and 50 g glucose orally. Plasma glucose, insulin, C-peptide, glucagon, urea nitrogen, alpha-amino acid nitrogen, and lactate concentrations were measured, and net 5-h postprandial areas were calculated. The net glucose-area response to the ingested glucose dose (with the 0-time value as a constant baseline) was best described by a second-order polynomial equation, whereas insulin-area response was best described by a third-order equation. In a separate study, 5 untreated type II diabetic subjects were given only water, and the same metabolites and hormones were measured. Data from this study indicated that the baseline was not constant during the 5 h of study but decreased progressively. The net glucose-area and insulin-area responses to ingested glucose dose (with the decreasing baseline) were then best described by third-order equations. Glucagon, alpha-amino acid nitrogen, and lactate concentrations were exquisitely sensitive to a rise in glucose and insulin concentrations. These were all decreased with the lowest concentration of glucose used. At this dose of glucose, the increase in insulin was only 15 microU/ml.

Acute metabolic response to high-carbohydrate, high-starch meals compared with moderate-carbohydrate, low-starch meals in subjects with type 2 diabetes.

OBJECTIVE: The monosaccharides resulting from the digestion of ingested carbohydrates are glucose, fructose, and galactose. Of these three monosaccharides, only ingested glucose resulted in a large increase in the plasma glucose concentration. Fructose (Metabolism 41:510-517, 1992) and galactose (Metabolism 42:1560-1567, 1993) had only a minor effect. Therefore, we were interested in determining whether we could design a mixed meal, using foods of known monosaccharide, disaccharide, and starch composition, the ingestion of which would result in only a small rise in plasma glucose concentration. RESEARCH DESIGN AND METHODS: The experimental meal was composed of very little readily digestible starch but rather large amounts of fruits and vegetables. It contained 43% carbohydrate, 22% protein, and 34% fat. The results were compared with a second type of meal that contained 55% carbohydrate, 15% protein, and 30% fat, with an emphasis on complex carbohydrates (starch). It also was compared with a third meal that contained 40% carbohydrate, 20% protein, and 40% fat, typical of that consumed by the average American. The test meals were ingested in random order by people with type 2 diabetes who were not treated with oral hypoglycemic agents or insulin. Each subject ingested each type of meal. The same identical meal was ingested at 0800, 1200, and 1700. RESULTS: The integrated 24-h plasma glucose area response was statistically significantly smaller (P < 0.05) after ingestion of the low-starch meals compared with the high-starch, high-carbohydrate meals or the typical American meals. The 24-h integrated serum insulin area response also was statistically significantly less (P < 0.05) after ingestion of the low-starch meals compared with the high-starch meals or the typical American meals. The serum triglyceride area response was similar after ingestion of all three test diets. CONCLUSIONS: A diet in which fruits, nonstarch vegetables, and dairy products are emphasized may be useful for people with type 2 diabetes.

Effect of protein ingestion on the glucose appearance rate in people with type 2 diabetes.

Amino acids derived from ingested protein are potential substrates for gluconeogenesis. However, several laboratories have reported that protein ingestion does not result in an increase in the circulating glucose concentration in people with or without type 2 diabetes. The reason for this has remained unclear. In people without diabetes it seems to be due to less glucose being produced and entering the circulation than the calculated theoretical amount. Therefore, we were interested in determining whether this also was the case in people with type 2 diabetes. Ten male subjects with untreated type 2 diabetes were given, in random sequence, 50 g protein in the form of very lean beef or only water at 0800 h and studied over the subsequent 8 h. Protein ingestion resulted in an increase in circulating insulin, C-peptide, glucagon, alpha amino and urea nitrogen, and triglycerides; a decrease in nonesterified fatty acids; and a modest increase in respiratory quotient. The total amount of protein deaminated and the amino groups incorporated into urea was calculated to be approximately 20-23 g. The net amount of glucose estimated to be produced, based on the quantity of amino acids deaminated, was approximately 11-13 g. However, the amount of glucose appearing in the circulation was only approximately 2 g. The peripheral plasma glucose concentration decreased by approximately 1 mM after ingestion of either protein or water, confirming that ingested protein does not result in a net increase in glucose concentration, and results in only a modest increase in the rate of glucose disappearance.

Metabolic response to glucose ingested with various amounts of protein.

Seven healthy, normal-weight subjects were fed breakfasts of 50 g protein, 50 g glucose, and 10, 30, or 50 g protein plus 50 g glucose in random sequence. Plasma glucose, insulin, C peptide, glucagon, nonesterified fatty acids, and alpha-amino nitrogen were then measured from samples obtained over 4 h. The postmeal net area of each response curve was calculated. Ingestion of 50 g protein alone did not change the serum glucose concentration. The various amounts of protein ingested with 50 g glucose also did not alter the serum glucose response compared with that observed with 50 g glucose alone. Ingestion of the various amounts of protein also did not result in a further increase in insulin concentration when ingested with glucose, except with the 50-g-protein dose. This increase was modest. Ingestion of glucose resulted in a decrease in alpha-amino nitrogen and glucagon concentrations whereas ingestion of protein increased them as expected. Additions of progressively larger amounts of protein to the glucose meal resulted in a progressive increase in the alpha-amino-nitrogen- and glucagon-area responses. The relationship was curvilinear for both the alpha-amino-nitrogen response and the glucagon response. The null point, that is, the protein dose ingested with 50 g glucose at which there would be no change in area response, was estimated to be 9 g protein for alpha-amino nitrogen and 5 g protein for glucagon.

The effect of protein ingestion on the metabolic response to oral glucose in normal individuals.

Eight normal subjects were given 50 g protein, 50 g glucose, or 50 g protein + 50 g glucose. Plasma glucose, insulin, C-peptide, glucagon, alpha-amino nitrogen (AAN), and nonesterified fatty acid (NEFA) responses were then determined over 4 h. Protein stimulated only a modest insulin rise and the area above fasting baseline was only 28% of that after glucose. The sum of the serum insulin area following protein ingestion and that following glucose ingestion was 100.4% of the combination meal. C-peptide changes confirmed the insulin response. The addition of glucose to the protein meal resulted in a 60 min delay in glucagon and AAN rise compared to the protein meal alone. Subsequently AAN and glucagon increased to levels greater than or equal to those observed after protein ingestion alone. In summary, protein is a much less potent secretagogue for insulin than is glucose in normal individuals, and the effect on insulin secretion is not synergistic. Addition of glucose to a protein meal results in a delayed rise in AAN and glucagon concentrations in normal subjects.

Regulation of glycogen synthesis in the liver.

The glycogen synthase-mediated reaction is rate-limiting for glycogen synthesis in the liver. Glycogen synthase has been purified essentially to homogeneity and has been shown to be a dimer composed of identical subunits. It is regulated by a phosphorylation-dephosphorylation mechanism, catalyzed by kinases and a phosphatase. The subunits of synthase D, the most phosphorylated form, each contain approximately 17 phosphates. The subunits of synthase I, the least phosphorylated form, each contain 14 phosphates. Thus, during the transition between these two forms, a net of three phosphoryl groups is added or removed. In synthase D, six of the phosphates are alkali-labile. In synthase I, three of the phosphates are alkali-labile. Therefore, all of the phosphorylation sites important in the interconversion of these two forms are alkali-labile (attached to serine or threonine residues). In short-term experiments using isolated hepatocytes, [32P]phosphate was only incorporated into the alkali-labile sites and the phosphate in these sites was shown to turn over rapidly. Glucose addition, which is known to reduce the proportion of synthase in the D form when assayed kinetically, also reduced the [32P]phosphate content. Glucagon addition, which increases the proportion of synthase in the D form, increased it. These changes do not appear to be site-specific. Ingestion or administration of fructose, or galactose, as well as glucose, result in a shift in synthase equilibrium in favor of the less phosphorylated forms. Possible mechanisms by which synthase phosphatase activity may be increased after ingestion of glucose or fructose, and thus shift the equilibrium in favor of the less phosphorylated forms, are discussed. The mechanism by which galactose may stimulate the phosphatase reaction is completely unknown.

The effect of oral casein on hepatic glycogen metabolism in fasted rats.

Casein hydrolysate administration to fasted rats resulted in a biphasic response of glycogen synthase. Fifteen minutes after the protein meal, synthase R (active form) was increased. This was associated with a transient increase in hepatic glucose and glucose-6-phosphate (G6P) concentrations. Both glucose and G6P are known to stimulate synthase phosphatase activity, which would result in activation of synthase. Portal plasma insulin concentration was directly related to the amount of synthase R present. By 1 hour after the meal, synthase R activity was decreased compared with the control activity. Hepatic glycogen concentration was variable during the first 30 minutes after the meal, and then decreased progressively. Portal plasma glucagon concentration and phosphorylase a activity were elevated at all time points. The data suggest that the increased portal plasma glucagon concentration is the major hormonal signal for glycogen metabolism during the second hour following a pure protein meal. However, during the first 30 minutes glycogenolysis is attenuated, perhaps due to the transient increase in insulin and an increased intracellular G6P concentration.

Metabolic response to egg white and cottage cheese protein in normal subjects.

In type II diabetic subjects, we previously demonstrated differences in the serum insulin, C-peptide, and glucagon response to ingestion of seven different protein sources when administered with 50 g of glucose. The response was smallest with egg white and greatest with cottage cheese protein. In the present study, we compared the responses to 50 g of the above two proteins ingested without glucose in normal male subjects. We also determined the proportion of each ingested protein converted to urea nitrogen. The incremental area response integrated over 8 hours for serum insulin, C-peptide, glucagon, alpha-amino-nitrogen (AAN), and urea nitrogen were all approximately 50% less following egg white. This was associated with a 50% smaller conversion of protein to urea. Overall, 70% of the cottage cheese but only 47% of the egg white protein could be accounted for by urea formation. Most likely the smaller hormonal response to egg white is due to poor digestibility of this protein.

Acute effects of ingestion of carbohydrate, protein, or fat on cardiac glycogen metabolism in rats.

Administration of large doses of insulin to intact rats has been shown to stimulate cardiac glycogen synthase phosphatase activity. This results in an activation of glycogen synthase. However, whether a more physiologic stimulus for insulin secretion also resulted in activation of synthase had not been studied. In the present study, rats were fed glucose, casein hydrolysate, or a mixed meal after a 24-hour fast as a means of physiologically stimulating insulin secretion. Lard was fed as a noninsulinotropic nutrient for comparative purposes. Plasma insulin was significantly increased by 15 minutes in rats given a mixed meal or glucose, but surprisingly, no change was observed in rats fed casein hydrolysate. As expected, no change in plasma insulin was observed in rats fed lard. Synthase phosphatase activity was stimulated in rats fed a mixed meal, glucose, or casein hydrolysate, but not in rats fed lard. Likewise, the proportion of synthase in the active (I) form was significantly increased in rats fed a mixed meal, glucose, or casein hydrolysate, but not in rats fed lard. The increase in phosphatase activity and the increased proportion of synthase in the active form following ingestion of casein hydrolysate was unexpected since this occurred in the absence of an increase in insulin. The proportion of phosphorylase in the active (a) form decreased in rats fed glucose, but remained unchanged in rats fed a mixed meal, casein hydrolysate, or lard. The cardiac glycogen concentration decreased dramatically in rats fed casein hydrolysate. Following the other meals, there was either no change or the decrease was modest.(ABSTRACT TRUNCATED AT 250 WORDS)