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F Q Nuttall

Publications and source records attributed to F Q Nuttall.

At least 37 records · Page 2Linked to original sources
PubMed1998

Comparison of percent total GHb with percent HbA1c in people with and without known diabetes.

OBJECTIVE: To directly compare results obtained using an ion-exchange high-performance liquid chromatography (HPLC) HbA1c method used in the Diabetes Control and Complications Trial with two different affinity chromatography methods in which "total GHb" is determined. RESEARCH DESIGN AND METHODS: Blood was obtained from a large number of people with and without known diabetes. The specimens were divided and assayed for HbA1c and for total GHb. Total GHb was determined using a semi-automated gravity-elution boronate affinity chromatography method and an automated boronate affinity HPLC method. The results obtained with the two methods were also compared. RESULTS: In subjects without known diabetes, the mean percentage HbA1c and the range of values were similar to the total GHb values in the same subjects when assayed using the semi-automated affinity gravity-elution method (mean 5.2 +/- 0.4 and 5.1 +/- 0.4% [SD], respectively). With the affinity HPLC method, results were 5.3 +/- 0.4%. The similarity in results was surprising. However, analysis of the data suggests that a large proportion of the material in the HbA1c fraction measured using this ion-exchange HPLC method is not GHb, as pointed out by others. Although the results were similar in people without known diabetes, in the people with diabetes, the incremental increase was approximately 25% greater for the total GHb when compared with the increase in HbA1c. When corrected for the non-GHb being measured by the HbA1c method, it can be calculated that approximately 40% more GHb is measured using affinity chromatography over the entire range of GHb values. CONCLUSIONS: The similarity in the mean and range of percent HbA1c and in percent total GHb using these different methods can be attributed to two factors: 1) the HbA1c ion-exchange method measures only approximately 50-60% of the total GHb present, and 2) approximately 40-50% of the material being measured in the HbA1c fraction is not GHb, i.e., offsetting factors fortuitously resulted in values similar to the more specific affinity methods. The greater incremental increase in percent total GHb compared with percent HbA1c in people with diabetes can be attributed to the greater amount of GHb being measured with the affinity methods.

Adolescent↗
PubMed1998

Liver glycogenin activity in diabetic and adrenalectomized rats.

The glycogen concentration in liver is altered in various pathophysiologic states. In fasted rats, it is higher in diabetic, and lower in adrenalectomized rats compared to control animals. In fed rats, it is lower in diabetic, and little changed in adrenalectomized animals compared to controls. We were interested in determining whether the activity of glycogenin, a self-glycosylating protein that initiates the synthesis of new glycogen molecules, could explain these differences in liver glycogen concentration. Glycogenin activity was measured by the incorporation of 14C-glucose from UDP-U-14C-glucose into an acid-precipitable product before and after amylase treatment of liver extracts. The glycogenin activity was similar in normal, diabetic and adrenalectomized fasted animals, regardless of the hepatic glycogen concentration. In fasted rats, glycogenin was present predominantly as the free-form of the enzyme, i.e., not attached to an amylase-digestible glycan, presumably glycogen. In contrast, in fed rats, the majority, if not all of the glycogenin was incorporated into a glycogen-like (proteoglycan) molecule. Proteoglycan synthase activity, previously identified in normal fed rats, also was present in diabetic and adrenalectomized fed rats, and the activity was similar. Thus, the altered ability to store hepatic glycogen in diabetic fed and fasted and adrenalectomized fasted rats cannot be explained by decreases in glycogenin or proteoglycan synthase activities, at least as measured using the present assays.

Adrenalectomy↗
PubMed1998

Nutrition and the management of type 2 diabetes.

Nutritional recommendations for patients with type 2 diabetes have changed dramatically over the last 60 years. We present a review of the evolution of these recommendations, as well as a comprehensive overview of the current recommendations for specific food components. The general principles of the nutritional management of type 2 diabetes are: (1) Dietary recommendations for patients with diabetes should be similar to those for the general population; (2) Dietary recommendations should be flexible and highly individualized for the patient and his or her family; (3) Table sugar or foods containing sugar do not need to be restricted to a level less than in a typical American diet; (4) Readily digestible starches raise the blood glucose more than sugars; (5) The effects of weight loss on glycemic control will occur within 2 or 3 months, after which more definitive therapies should be instituted; and (6) Patients should not be stigmatized for failing to lose weight, and weight cycling should be discouraged. Nutritional interventions should concentrate on reducing known risk factors for cardiovascular disease and maintaining glycemic control without jeopardizing the quality of life, the health, or the safety of the patient.

Diabetes Mellitus, Type 2↗
PubMed1997

Effect of feeding, fasting, and diabetes on liver glycogen synthase activity, protein, and mRNA in rats.

Hepatic glycogen synthase activity is increased in diabetic animals. However, the relationship between enzymic activity, enzyme protein mass, and mRNA abundance has not been well characterized. In the present study, these relationships were determined in 3- and 8-day diabetic, fed and fasted rats. The results were compared to data obtained in normal fed and fasted animals. In normal rats, total synthase specific activity and protein mass were similar in the fed and fasted state. However, in fed animals, the synthase mRNA abundance was increased 1.7-fold. In 3-day diabetic rats, total synthase specific activity was increased approximately 29% compared to normal controls. It was unaffected by feeding and fasting and was associated with an approximate 15% increase in enzyme mass. Synthase mRNA was increased 1.8 and 2.6-fold in fasted and fed animals, respectively. In 8-day diabetic rats, total synthase specific activity was increased more than 2-fold compared to controls. However, the enzyme protein mass was decreased by approximately 20%. The mRNA abundance in 8-day diabetic fasted rats was only 30% of controls, while in fed rats it was increased by 40%. These data indicate that feeding and fasting have a major effect on synthase mRNA abundance which is independent of synthase activity, or protein mass, or both, in normal and diabetic animals. Total synthase specific activity increased with duration of diabetes. This was associated with only a modest change in protein mass. Thus, diabetes induces an increase in synthase catalytic efficacy. The specific activity of phosphorylase is decreased in diabetic rats.

Analysis of Variance↗
PubMed1997

The effect of caffeine and caffeine analogs on rat liver phosphorylase a activity.

Liver phosphorylase a is stimulated by adenosine monophosphate. It is inhibited by adenosine diphosphate, adenosine triphosphate and glucose. Using these effectors as well as other potential in vivo effectors at concentrations approximating those present in hepatocytes, we previously reported that the net effect was nil, i.e., at estimated in vivo concentration, the inhibitors neutralized the stimulatory effect of adenosine monophosphate in a phosphorylase a preparation. In addition, a concentration dependent inhibition by glucose was not present. Therefore, we were interested in determining if addition of caffeine, an inhibitor that synergizes with glucose, would result in a reduction in activity in the presence of the other effectors and restore regulation by physiological concentrations of glucose. The effect of xanthine and xanthine analogs also were studied. Purified liver phosphorylase a was used. Activity was measured in the direction of glycogenolysis at 37 degrees, pH 7.0 and under initial rate conditions. Caffeine (1 mM) was added to individual and various combinations of other effectors. The interactions among the potential in vivo effectors when caffeine was present were complex. However, when caffeine was present glucose again regulated activity. This most likely was due to a synergistically facilitated reduction in binding affinity for AMP by caffeine and glucose. Theophylline and adenosine did not inhibit activity but reduced AMP stimulation and facilitated glucose inhibition. Xanthine and the other xanthine derivatives all strongly inhibited activity and the inhibition was independent of other effectors.

Adenine Nucleotides↗
PubMed1996

Allosteric regulation of liver phosphorylase a: revisited under approximated physiological conditions.

Phosphorylase removes glucosyl units from the terminal branches of glycogen through phosphorolysis, forming glucose-1-P. It is present in two interconvertible forms, phosphorylase a and b. The a form is the active form and is rate limiting in glycogen degradation. The activities of phosphorylase a and of total phosphorylase as conventionally measured exceed the activities of glycogen synthase R (active form) and of total synthase by approximately 10- and 20-fold. Thus, unless phosphorylase a is inhibited or compartmentalized or its substrates are exceedingly low in vivo, net glycogen synthesis could not occur. In addition, following an administered dose of glucose, phosphorylase a activity changes little when glycogen is being synthesized, is stable, or is being degraded, suggesting an important role for allosteric effectors in regulation. Therefore, we have determined the effect of potential modifiers of enzyme activity at estimated intracellular concentrations. Purified liver phosphorylase a was used. Activity was measured in the direction of glycogenolysis, at 37 degrees C, pH 7.0, and under initial rate conditions. Both a Km and a near-saturating concentration of inorganic phosphate (substrate) were used in the assays. A physiological concentration of AMP was saturating. It decreased the Km for Pi by approximately 50% and stimulated activity. ADP, ATP, and glucose inhibited activity. Fructose-1-P inhibited activity only at a high and nonphysiological concentration. Glucose-6-P and UDP-glucose were not significant inhibitors. Inhibition of activity by ADP was little affected by the addition of AMP. However, AMP partially abolished the inhibitory effect of ATP and completely abolished the inhibitory effect of glucose. When AMP, ADP, ATP, glucose-6-P, UDP-glucose, glucose, and fructose-1-P were added together, the net effect was no change in phosphorylase a activity compared to the activity without any effectors. In addition, changes in glucose concentration did not affect activity. K glutamine modestly stimulated activity. Numerous other metabolites were tested and were without effect. The present data indicate that the known endogenous allosteric effectors cannot explain the smaller than expected in vivo phosphorylase a activity or the regulation of phosphorylase a activity.

Adenine Nucleotides↗
PubMed1996

Effect of 24 hours of starvation on plasma glucose and insulin concentrations in subjects with untreated non-insulin-dependent diabetes mellitus.

Adherence to a low-calorie diet often results in a decrease in blood glucose concentration in persons with non-insulin-dependent diabetes mellitus (NIDDM). Whether this is due to the resultant weight loss or to a decrease in caloric intake has been uncertain. We have obtained data previously that indicated a very short-term reduction in caloric intake (5 hours) resulted in a significant decrease in plasma glucose concentration in subjects with NIDDM. The purpose of the present study was to determine if a further decrease in glucose would occur if the fast was extended from 5 to 24 hours. Seven male subjects with untreated NIDDM were studied after an 11-hour overnight fast. For the subsequent 24-hour period, subjects were given only water. Blood was obtained for glucose, insulin, C-peptide, triglycerides, nonesterified fatty acids (NEFA) alpha-amino acid nitrogen, urea nitrogen, and glucagon at hourly intervals for 24 hours beginning at 8 AM. The amount of glycogen degraded was calculated based on the potassium balance. Plasma glucose decreased from 158 mg/dL at 8 AM to a nadir of 104 mg/dL at 7 PM. It then increased by 30 mg/dL. Corresponding changes occurred in insulin and C-peptide. Serum glucagon remained unchanged. Serum alpha-amino acid nitrogen and urea nitrogen decreased. Triglycerides and NEFA increased. The calculated glycogen utilized over this period was approximately 167 g. This would provide approximately 700 kcal energy. The elevated blood glucose concentration in mild to moderately severe untreated NIDDM subjects was normalized following short-term fasting. Plasma insulin concentrations also decreased to within normal limits. These decreases were highly significant. Glycogenolysis is an important source of fuel during this period.

Aged↗
PubMed1995

Glycogen concentration and regulation of synthase activity in rat liver in vivo.

The proportion of liver glycogen synthase in the active (R+I) forms is lower in the fed than in the fasted state. This has been attributed to inhibition of synthase phosphatase by the accumulated hepatic glycogen. We observed that after oral administration of glucose or galactose to fasted rats, hepatic synthase R+I activity first increased, as expected, but then decreased to a nadir significantly below the control level regardless of the maximal glycogen concentration reached. Therefore, we investigated further the relationship of hepatic synthase R+I activity and glycogen concentration in vivo in fasted rats given increasing oral glucose loads. Male rats fasted 24 h were given glucose doses of 0.1-4.0 g/kg by oral gavage (n > or = 8). Liver synthase R+I, total synthase, phosphorylase a, glucose, glycogen, glucose-6-P, and UDP glucose were measured at intervals over 20-240 min after gavage. Even the smallest glucose load elicited rapid glycogen synthesis. The maximum glycogen concentration increased linearly with the size of the glucose load, although the proportion of administered glucose accounted for by liver glycogen decreased as the glucose load increased. The proportion of synthase in the active (R+I) forms peaked at 20 min after all doses and then declined. By the time the glycogen concentration was maximal, synthase R+I activity had decreased to the control value, regardless of the glucose dose administered or the maximum glycogen concentration reached. Although the decrease in synthase R+I at the time of the glycogen peak was correlated with the increase in glycogen concentration, synthase R+I continued to decrease for another 1-2 h even though liver glycogen was stable or decreasing. The nadir reached was independent of the maximal glycogen concentration. The synthase R+I nadir also did not correlate with hepatic glucose or glucose-6-P concentrations or phosphorylase a activity. Overall, there was not a straightforward temporal or quantitative relationship between the glycogen concentration and synthase R+I activity. These data suggest a more complex mechanism than simply direct inhibition of synthase phosphatase by glycogen.

Animals↗
PubMed1995

Physiological doses of oral casein affect hepatic glycogen metabolism in normal food-deprived rats.

In a previous study, administration of casein hydrolysate to food-deprived rats at a dose of 4 g/kg body wt resulted in an increase in portal plasma glucagon concentration. This was associated with an activation of phosphorylase a and a decrease in hepatic glycogen concentration. The present study was undertaken to determine whether similar results would be obtained with smaller doses. Doses of 1 and 2 g/kg body wt were administered to food-deprived rats. At a dose of 2 g/kg, portal plasma glucagon concentration was significantly elevated. This was associated with a slight increase in phosphorylase a activity (P < 0.05) and a 50% decrease in hepatic glycogen concentration (P < 0.01). At a dose of 1 g casein hydrolysate/kg body wt, changes in portal plasma glucagon concentration, phosphorylase a activity and hepatic glycogen concentration generally were not observed. Hepatic glucose, uridine diphosphoglucose, ATP and glucose-6-phosphate concentrations were unaffected by either dose of casein hydrolysate. The data indicate a dose-response relationship between casein hydrolysate administration and effects on glycogen metabolism in the liver. Protein-induced glycogenolysis is likely to occur when rats ingest a moderate amount of a pure protein meal.

Adenosine Triphosphate↗
PubMed1995

Effects of glucagon with or without insulin administration on liver glycogen metabolism.

Rats fed ad libitum were given insulin alone (4 U/kg), glucagon alone (25 micrograms/kg), or insulin and glucagon sequentially. Phosphorylase a and synthase R activities, hepatic glycogen, uridine diphosphoglucose, inorganic phosphate (Pi), and plasma glucose, lactate, glucagon, and insulin concentrations were determined over the subsequent 40 min. In separate animals, muscle extraction of 2-deoxy-D-[3H]glucose also was determined. After glucagon administration, glycogen phosphorylase a and plasma glucose were increased within 5 min. However, the glycogen concentration did not decrease for 20 min. Glucagon administration to rats pretreated with insulin stimulated a similar increase in phosphorylase a activity. Again, glycogen was not degraded for 20 min. After insulin only, glycogen concentration remained unchanged. Plasma glucose decreased as expected. In each group, muscle extraction of 2-deoxy-D-[3H]glucose increased compared with the controls (P < 0.05). In summary, glucagon and/or insulin administration did not stimulate significant glycogen degradation for 20 min, even though phosphorylase was activated. The mechanism remains to be determined.

Animals↗
PubMed1995

Veterans Affairs Cooperative Study on glycemic control and complications in type II diabetes (VA CSDM). Results of the feasibility trial. Veterans Affairs Cooperative Study in Type II Diabetes.

OBJECTIVE: It is not clear whether intensive pharmacological therapy can be effectively sustained in non-insulin-dependent diabetes mellitus (NIDDM). The relative risks and benefits of intensive insulin therapy in NIDDM are not well defined. Accordingly, we designed a feasibility study that compared standard therapy and intensive therapy in a group of NIDDM men who required insulin due to sustained hyperglycemia. RESEARCH DESIGN AND METHODS: A prospective trial was conducted in five medical centers in 153 men of 60 +/- 6 years of age who had a known diagnosis of diabetes for 7.8 +/- 4 years. They were randomly assigned to a standard insulin treatment group (one morning injection per day) or to an intensive therapy group designed to attain near-normal glycemia and a clinically significant separation of glycohemoglobin from the standard arm. A four-step plan was used in the intensive therapy group along with daily self-monitoring of glucose: 1) an evening insulin injection, 2) the same injection adding daytime glipizide, 3) two injections of insulin alone, and 4) multiple daily injections. Patient accrual and adherence, glycohemoglobin (HbA1c), side effects, and measurements of endpoints for a prospective long-term trial were assessed. RESULTS: Accrual goals were met, mean follow-up time was 27 months (range 18-35 months), and patients kept 98.6% of scheduled visits. After 6 months, the mean HbA1c in the intensive therapy group was at or below 7.3% and remained 2% lower than the standard group for the duration of the trial. Most of the decrease in the mean HbA1c in the intensive group was obtained by a single injection of evening intermediate insulin, alone or with daytime glipizide. By the end of the trial, 64% of the patients had advanced to two or more injections of insulin a day, aiming for normal HbA1c. However, only a small additional fall in HbA1c was attained. Severe hypoglycemia was rare (two events per 100 patients per year) and not significantly different between the groups, nor were changes in weight, blood pressure, or plasma lipids. There were 61 new cardiovascular events in 40 patients and 10 deaths (6 due to cardiovascular causes). CONCLUSIONS: Intense stepped insulin therapy in NIDDM patients who have failed glycemic control on pharmacological therapy is effective in maintaining near-normal glycemic control for > 2 years without excessive severe hypoglycemia, weight gain, hypertension, or dyslipidemia. Cardiovascular event rates are high at this stage of NIDDM. A long-term prospective trial is needed to assess the risk-benefit ratio of intensified treatment of hyperglycemia in NIDDM patients requiring insulin.

Aged↗
PubMed1994

Liver glycogen synthase, phosphorylase, and the glycogen concentration in rats given a glucose load orally: a 24-hour study.

Fasted rats were given 4 g/kg glucose orally. Synthase R (active forms), total synthase, and phosphorylase alpha activities, and hepatic glycogen, glucose 6-phosphate (glucose-6P), uridine diphosphoglucose (UDP-glucose), glucose, and plasma glucose concentrations were determined over the subsequent 24 h. The resulting glycogen concentration changes could be divided into three distinct phases. A glycogen synthetic phase (between 0 and 4 h), a stability phase (between 4 and 12 h), and a degradation phase (between 12 and 24 h). Synthase R activity increased rapidly and reached a maximum at 20 min. With the onset of glycogen synthesis it gradually decreased below the control values, reaching a nadir by 4 h. During the glycogen stability phase it gradually increased again up to the control value. It then remained stable during the subsequent glycogen degradation phase. Phosphorylase a activity did not change throughout the entire 24-h period. Glucose-6-P concentration increased almost twofold at 20 min. It then decreased but was above the control values at the 24th h. The plasma and hepatic glucose concentrations increased as expected after the glucose load. They then decreased but remained above the control value at all subsequent time points. In summary, the synthase R, phosphorylase a activities, or changes in the known allosteric modifiers of these enzymes could not explain the changes in glycogen concentration. The reasons for these discrepancies remain to be determined.

Administration, Oral↗
PubMed1994

Incorporation of glycogenin into a hepatic proteoglycogen after oral glucose administration.

Glycogenin is a 37-kDa protein upon which new glycogen molecules are considered to be constructed. Therefore, we were interested in determining its role in liver glycogen synthesis following glucose administration. Twenty-four-hour fasted rats were given 4 g/kg glucose orally. Glycogenin and synthase R activities and glycogen were determined over the subsequent 24 h. In fasted rats given just water, glycogenin activity was present and did not change over the subsequent 24 h. Following glucose, glycogenin activity also was not different for 1 h, i.e. the glycogenin was not incorporated into glycogen even though the glycogen concentration had increased. Subsequently, the glycogenin activity became unmeasurable. Presumably, the glycogenin was incorporated into a proteoglycan product since after amylase treatment, glycogenin activity was again present and was quantitatively unchanged. Free glycogenin activity remained unmeasurable until after 12 h. At this time, glycogen began to decrease, and, by 15 h, free glycogenin activity again appeared. The results indicate that in fasted rats, essentially all of the glycogenin was free. Following administration of oral glucose, glycogenin was incorporated into a proteoglycan product but only 60 min after glycogen synthesis had begun. Free glycogenin did not reappear until the 15th h after glucose was given and after the glycogen concentration had decreased by approximately 60%.

Administration, Oral↗
PubMed1994

Primary structure of human liver glycogen synthase deduced by cDNA cloning.

The cDNA for human liver glycogen synthase was isolated by screening a human liver cDNA library constructed in lambda gt11. The full cDNA was 2912 bp in length. It coded for a protein of 703 amino acid residues with a molecular mass of 80.9 kDa. The number of amino acids was identical to and the deduced amino acid sequence homology was 92% that of the rat liver enzyme. The human and rat liver glycogen synthases are truncated by 34 amino acids compared to the human muscle enzyme, and by 32 amino acids compared to the rabbit muscle enzyme. The amino acid similarity between human liver and human muscle glycogen synthase was only 69%. It was least similar in the N and C terminal regions of the molecule. Two highly conserved regions are present in all published amino acid sequences for glycogen synthase, including those of the two yeast enzymes. These regions include the amino acid sequences from 201 to 400 and 501 to 600. This high conservation suggests that the catalytic site and the glucose-6-P and nucleotide allosteric sites are included in these regions.

Amino Acid Sequence↗
PubMed1994

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.

Adult↗
PubMed1993

Allosteric regulation of glycogen synthase in liver. A physiological dilemma.

Glycogen synthase catalyzes the transfer of the glucosyl moiety from UDP-glucose to the terminal branch of the glycogen molecule and is considered to be the rate-limiting enzyme for glycogen synthesis. However, under ideal assay conditions, i.e. 37 degrees C with saturating concentrations of UDP-glucose and the activator, glucose-6-P, the maximal catalytic activity of glycogen synthase was only 78% of the in vivo glycogen synthetic rate. Using concentrations of UDP-glucose and glucose-6-P likely to be present in vivo, the rate was only approximately 30%. This prompted us to reassess a possible role of allosteric effectors on synthase activity. Glycogen synthase was assayed at 37 degrees C using dilute, pH 7.0, buffered extracts, initial rate conditions, and UDP-glucose and glucose-6-P concentrations, which approximate those calculated to be present in total liver cell water. Several allosteric effectors were tested. Magnesium and AMP had little effect on activity. Pi, ADP, ATP, and UTP inhibited activity. When a combination of effectors were added at concentrations approximating those present in cell water, synthase activity could account for only 2% of the glycogen synthetic rate. Thus, although allosteric effectors are likely to be playing a major role in regulating synthase enzymic activity in liver cells, to date, a metabolite that can stimulate activity and/or overcome nucleotide inhibition has yet to be identified. If such a metabolite cannot be identified, an additional or alternative pathway for glycogen synthesis must be considered.

Adenosine↗