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Biomedical subjects

Mary C Gannon

Publications and source records attributed to Mary C Gannon.

7 recordsLinked to original sources

A solubilized cellulose fiber decreases peak postprandial cholecystokinin concentrations after a liquid mixed meal in hypercholesterolemic men and women.

Viscous dietary fibers can modify the alimentary responses to a meal and improve glucose tolerance. There may be a relationship between the effect of these fibers in the gut and the ability of the hormone cholecystokinin (CCK) to slow gastric emptying and affect glucose homeostasis. We investigated the acute and long-term (adaptive) glucose and CCK responses to liquid mixed test meals, with or without 5 g of solubilized cellulose (SC), a novel viscous fiber, in 33 hypercholesterolemic men and women. In the acute study, there was a lower peak CCK concentration (P = 0.01) after a SC-containing test meal compared with a fiber-free test meal. The CCK area under the curve responses also tended to be lower after the fiber-containing meal (P = 0.08). After a 6-wk intervention with 2.5 g of SC or placebo twice daily, fasting plasma glucose concentration tended to decrease in the SC group, whereas it increased in the control group (for between-group difference in change, P = 0.13). There were no differences between the groups in the changes from baseline to the end of the study in any other variable. There were significant gender differences in several variables at baseline. These findings support the hypothesis that CCK may mediate the effect of viscous fibers on glucose metabolism. The gender differences in glucose and CCK may explain some of the discrepancies in the results of similar experiments reported to date.

Adult↗

The metabolic response of subjects with type 2 diabetes to a high-protein, weight-maintenance diet.

In a randomized, crossover 5-wk study design, we recently reported that a weight-maintaining diet in which the percentage of total food energy as protein was increased from 15-30% resulted in a decrease in postprandial glucose and glycohemoglobin in people with untreated type 2 diabetes without a significant change in insulin. Protein was substituted for carbohydrate in the diet. The fat content remained unchanged. In this publication, we present data on other hormones and metabolites that were considered to potentially be affected by substitution of protein for carbohydrate in the diet. The mean fasting plasma GH and total IGF-I concentrations were elevated on the 30% protein diet. The urinary free cortisol also was increased. However, the urinary aldosterone was unchanged. Although urinary pH was decreased, calcium excretion was not significantly increased. The plasma postprandial alpha-amino nitrogen concentrations were increased, but the 24-h integrated concentration was unchanged, indicating an accelerated amino acid removal rate. The plasma urea nitrogen was increased as expected. The urea production rate also was increased such that a new steady-state fasting value was present. The calculated urea production rate accounted for 97% of the protein ingested on the 15% protein diet, but only 80% on the 30% protein diet, suggesting net nitrogen retention on the high-protein diet. In conclusion, an increase in dietary protein results in a number of metabolic adaptations in addition to reducing the circulating glucose concentration. Serum TSH, total T(3), free T(4), B(12), folate, homocysteine, uric acid, and creatinine concentrations were unchanged.

Aldosterone↗

A fasting-induced decrease in plasma glucose concentration does not affect the insulin response to ingested protein in people with type 2 diabetes.

We previously have reported that protein, on a weight basis, is just as potent as glucose in increasing the insulin concentration in people with type 2 diabetes. In people without diabetes, protein is only approximately 30% as potent as glucose in this regard. In the present study, we tested the hypothesis that the increased insulin responsiveness to protein in people with type 2 diabetes is due to the elevated plasma glucose concentration in these individuals. Seven male subjects with untreated type 2 diabetes were given 50 g protein in the form of very lean beef at 8 AM after an overnight fast. On another occasion, the same individuals were fasted for an additional 24 hours to lower their plasma glucose concentration to near the normal reference range. They were then given 50 g protein. The 8 AM glucose concentration was lower after 24 hours of additional fasting, as expected. After ingestion of the protein meal, there was an unexpected, modest increase in glucose concentration after an additional 24 hours of fasting that was not observed with only an overnight fast. Despite the approximately 15% lower plasma glucose concentration at the time of the protein meal, the insulin responses were nearly identical. Thus, the greater insulin response to ingested protein is not likely to be due merely to a higher initial glucose concentration.

Aged↗

Oral arginine does not stimulate an increase in insulin concentration but delays glucose disposal.

BACKGROUND: Ingested protein increases circulating insulin concentrations. Several years ago it was also determined that an intravenously administered mixture of 10 essential amino acids stimulated insulin secretion. Of these, arginine was the most potent. The effect was synergistic with administered glucose. OBJECTIVE: Because the amounts of amino acid administered intravenously were very large and because ingested arginine is partially metabolized in the intestinal mucosa, we were interested in determining whether orally administered arginine stimulates a rise in circulating insulin concentration and whether arginine affects the glucose-induced rise in insulin concentration. DESIGN: Nine healthy subjects (4 women and 5 men aged 21-52 y) ingested 1 mmol arginine/kg lean body mass, 1 mmol arginine/kg lean body mass + 25 g glucose, 25 g glucose alone, and water only, in random order on separate occasions, at 0800. Blood samples were obtained at baseline and at 10-min intervals over the next 2 h and were assayed for glucose, insulin, glucagon, and amino acid concentrations. The half-time for gastric emptying was determined by scintigraphy. RESULTS: Unlike with intravenous administration, ingested arginine did not stimulate a rise in insulin concentration. The glucagon concentration was increased. Arginine attenuated and prolonged the glucose rise when it was ingested with glucose. Gastric emptying time was similar after ingestion of glucose alone or arginine plus glucose. CONCLUSION: Arginine, in an amount likely to be ingested in a high-protein meal, does not stimulate insulin secretion but attenuates the increase in glucose when given with glucose.

Administration, Oral↗

The metabolic response to ingested glycine.

BACKGROUND: The metabolic effects of dietary protein are complex. In persons with type 2 diabetes, protein ingestion results in little or no increase in plasma glucose concentrations but a stimulation of insulin and glucagon secretion. Furthermore, when protein is ingested with glucose, a synergistic effect on insulin secretion is observed. The most potent protein is gelatin, which consists of 30% glycine residues. OBJECTIVE: The objective of the present study was to determine whether glycine per se stimulates insulin secretion or reduces the glucose response when ingested with glucose. DESIGN: Nine healthy subjects were tested on 4 separate occasions. Plasma glucose, insulin, glucagon, and glycine concentrations were measured at various times during a 2-h period after the ingestion of 1 mmol glycine/kg lean body mass, 25 g glucose, 1 mmol glycine/kg lean body mass + 25 g glucose, or water only, given in random order. RESULTS: Plasma concentrations of glycine and glucagon were elevated after the ingestion of glycine, as expected. The serum insulin concentration also was slightly elevated after the ingestion of glycine alone. When glycine was ingested with glucose, the plasma glucose area response was attenuated by > 50% compared with the response after the ingestion of glucose alone. The dynamics of the insulin response after the ingestion of glycine plus glucose were modestly different from those after the ingestion of glucose alone, but the area response was not significantly different. CONCLUSION: The data are compatible with the hypothesis that oral glycine stimulates the secretion of a gut hormone that potentiates the effect of insulin on glucose removal from the circulation.

Adult↗

Integrated effects of multiple modulators on human liver glycogen phosphorylase a.

Hepatic glucose production is increased in people with type 2 diabetes. Glucose released from storage in liver glycogen by phosphorylase accounts for approximately 50% of the glucose produced after an overnight fast. Therefore, understanding how glycogenolysis in the liver is regulated is of great importance. Toward this goal, we have determined the kinetic characteristics of recombinant human liver glycogen phosphorylase a (HLGPa) (active form) and compared them with those of the purified rat enzyme (RLGPa). The Michaelis-Menten constant (K(m)) of HLGPa for P(i), 5 mM, was about fivefold greater than the K(m) of RLGPa. Two P(i) (substrate) concentrations were used (1 and 5 mM) to cover the physiological range for P(i). Other effectors were added at estimated intracellular concentrations. When added individually, AMP stimulated, whereas ADP, ATP and glucose inhibited, activity. These results were similar to those of the RLGPa. However, glucose inhibition was about twofold more potent with the human enzyme. UDP-glucose, glucose 6-phosphate, and fructose 1-phosphate were only minor inhibitors of both enzymes. We reported previously that when all known effectors were present in combination at physiological concentrations, the net effect was no change in RLGPa activity. However, the same combination reduced HLGPa activity, and the inhibition was glucose dependent. We conclude that a combination of the known effectors of phosphorylase a activity, when present at estimated intracellular concentrations, is inhibitory. Of these effectors, only glucose changes greatly in vivo. Thus it may be the major regulator of HLGPa activity.

Adenosine Diphosphate↗

Glucose uptake and glycogen levels are increased in pig heart after repetitive ischemia.

Repetitive myocardial ischemia increases glucose uptake, but the effect on glycogen is unclear. Thirteen swine instrumented with a hydraulic occluder on the circumflex (Cx) artery underwent 10-min occlusions twice per day for 4 days. After 24 h postfinal ischemia and in the fasted state, echocardiogram and positron emission tomography imaging for blood flow ([(13)N]-ammonia) and 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) uptake were obtained. Tissue was then collected for ATP, creatine phosphate (CP), glycogen, and glucose transporter-4 content, and hexokinase activity. After reperfusion, regional function and CP-to-ATP ratios in the Cx and remote regions were similar. Despite the absence of stunning, the Cx region demonstrated higher glycogen levels (33 +/- 11 vs. 24 +/- 11 micromol/g; P < 0.05), and this increase correlated well with the increase in FDG uptake (r(2) = 0.78; P < 0.01). Hexokinase activity was also increased relative to remote regions (0.62 +/- 0.29 vs. 0.37 +/- 0.19 IU/g; P < 0.05), with no difference in GLUT-4 content. In summary, 24 h after repetitive ischemia, glucose uptake and glycogen levels are increased at a time that functional and bioenergetic markers of stunning have recovered. The significant correlation between glycogen content and FDG accumulation in the postischemic region suggests that increased rates of glucose transport and/or phosphorylation are linked to increased glycogen levels in hearts subjected to repetitive bouts of ischemia.

Adenosine Triphosphate↗