Glucose appearance rate after the ingestion of galactose

Galactose is one of the monosaccharides of importance in human nutrition. It is converted to glucose-1-phosphate in the liver and subsequently stored as glycogen, or is converted to glucose and released into the circulation. The increase in plasma glucose is known to be modest following galactose ingestion. Whether this is due to a small increase in hepatic glucose output, or to a relatively large increase in hepatic glucose output but a concomitant increase in glucose disposal, is not known in humans. Therefore, the rates of glucose appearance (Ra) and disappearance (Rd) were determined over an 8-hour period in normal subjects using an isotope dilution technique. The subjects ingested 50 g galactose or water alone in random order at 8 AM on separate occasions. Plasma glucose, glucagon, lactate, urea nitrogen, total amino acids, and uric acid and serum insulin and triglycerides also were determined. Following galactose ingestion, there was a modest transient increase in peripheral glucose and insulin concentrations. This was associated with a modest increase in the glucose Ra. The calculated amount of glucose appearing in the circulation as a result of galactose ingestion was 9.8 g, while the amount of glucose disappearing over the 8 hours was 9.9 g. Thus, following ingestion of 50 g galactose by overnight-fasted men, approximately 20% appears as additional glucose in the circulation. Data obtained in animals suggest that a large amount of the galactose is stored as glucose in glycogen. Nevertheless, the conversion of galactose to glucose in the liver may have been greater than suggested by the increase in glucose appearance in the circulation due to substitution for other gluconeogenic substrates.     

The metabolic response to various doses of fructose in type II diabetic subjects.

Eight men with untreated type II diabetes were given 480 mL water containing 15 g, 25 g, 35 g, and 50 g fructose orally, in random sequence. The same subjects were given the same volume of water as a control. They also were given 50 g glucose on two occasions for comparative purposes. Plasma glucose, urea nitrogen, and glucagon, and serum insulin, C-peptide, alpha-amino-nitrogen (AAN), nonesterified fatty acids (NEFA), and triglycerides were determined over the subsequent 5-hour period. The area responses to each dose of fructose were calculated and compared with the water control. The integrated glucose area dose-response was curvilinear, with little increase in glucose until 50 g fructose was ingested. With the 50-g dose, the area response was 25% of the response to 50 g glucose. The insulin response also was curvilinear, but the curve was opposite to that of the glucose curve. Even the smallest dose of fructose resulted in a relatively large increase in insulin, and a near-maximal response occurred with 35 g. The area response to 50 g fructose was 39% of that to 50 g glucose. The C-peptide data were similar to the insulin data. The AAN area response to fructose ingestion was negative. However, the response was progressively less negative with increasing doses. The glucagon area response was positive, but a dose-response relationship was not apparent. The glucagon area response was negative after glucose ingestion, as expected. The urea nitrogen area response was negative, but again, a dose-response relationship to fructose ingestion was not present.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Effects of glucose, galactose, and lactose ingestion on the plasma glucose and insulin response in persons with non-insulin-dependent diabetes mellitus

Galactose usually is ingested as lactose, which is composed of equimolar amounts of glucose and galactose. The contribution of galactose to the increase in glucose and insulin levels following ingestion of equimolar amounts of galactose and glucose, or lactose, has not been reported in people with non-insulin-dependent diabetes mellitus (NIDDM). Therefore, we studied the effects of galactose ingestion alone, as well as with glucose either independently or in the form of lactose, in subjects with untreated NIDDM. Eight male subjects with untreated NIDDM ingested 25 g glucose, 25 g galactose with or without 25 g glucose, or 50 g lactose as a breakfast meal in random sequence. They also received 50 g glucose on two occasions as a reference. Water only was given as a control meal. Plasma galactose, glucose, glucagon, α-amino nitrogen (AAN), nonesterified fatty acids (NEFA), and serum insulin and C-peptide concentrations were determined over a 5-hour period. The integrated area responses were quantified over the 5-hour period using the water control as a baseline. Following ingestion of 25 g galactose, the maximal increase in plasma galactose concentration was 1 mmol/L. The mean maximal increases in plasma galactose concentration following ingestion of 25 g galactose + 25 g glucose or following 50-g lactose meals were similar and were only 12% of that following ingestion of galactose alone (P < .05). The mean galactose area response over the water control for the 25-g galactose meal was 0.95 ± 0.31 mmol · h/L. That following ingestion of 25 g glucose + 25 g galactose or following the 50-g lactose meal was 0.17 ± 0.07 and 0.13 ± 0.05 mmol · h/L, respectively. Following ingestion of 25-g or 50-g glucose meals, the galactose area responses increased only slightly. The mean glucose area response following the 50-g glucose meals was 14.8 ± 2.5 mmol · h/L. Glucose area responses following ingestion of 25 g galactose, 25 g glucose, 25 g glucose + 25 g galactose, and 50 g lactose were 11%, 49%, 54%, and 60% of that observed following ingestion of 50 g glucose, respectively. The mean insulin area response following ingestion of the 50-g glucose meals was 965 ± 162 pmol · h/L. The insulin area responses observed with 25 g galactose, 25 g glucose, 25 g glucose + 25 g galactose, and 50 g lactose were 24%, 51%, 81%, and 85% of that observed with the 50-g glucose meals, respectively. The C-peptide data confirmed the insulin data. The glucagon concentration was unchanged after galactose ingestion and decreased after glucose ingestion. However, the decrease in the glucagon area response observed with 25 g galactose + 25 g glucose or 50 g lactose was less than that with ingestion of 25 g glucose alone. The latter suggests inhibition of the glucagon response to glucose by the added galactose. In conclusion, ingested galactose results in only a modest increase in plasma glucose concentration. The glucose area responses to galactose and glucose are additive. Oral galactose is a relatively potent insulin secretagogue, and the insulin response is also additive to that following glucose ingestion. Ingestion of glucose with galactose markedly reduces the increase in plasma galactose concentration. The mechanism of this effect remains to be defined.     

The insulin and glucose responses to meals of glucose plus various proteins in type II diabetic subjects

We previously have shown that ingested beef protein is just as potent as glucose in stimulating a rise in insulin concentration in type II diabetic patients. A synergistic effect was seen when given with glucose. Therefore, we considered it important to determine if other common dietary proteins also strongly stimulate an increase in insulin concentration when given with glucose. Seventeen type II (non-insulin-dependent) untreated diabetic subjects were given single breakfast meals consisting of 50 g glucose, or 50 g glucose plus 25 g protein in the form of lean beef, turkey, gelatin, egg white, cottage cheese, fish, or soy. The peripheral plasma concentrations of glucose, insulin, glucagon, alpha amino nitrogen, urea nitrogen, free fatty acids, and triglycerides were measured. Following ingestion of the meals containing protein, the plasma insulin concentration was increased further and remained elevated longer compared with the meal containing glucose alone. The relative area under the insulin response curve was greatest following ingestion of the meal containing cottage cheese (360%) and was least with egg white (190%) compared with that following glucose alone (100%). The glucose response was diminished following ingestion of the meals containing protein with the exception of the egg white meals. The peripheral glucagon concentration was decreased following ingestion of glucose alone and increased following all the meals containing protein. The alpha amino nitrogen concentration varied considerably. It was decreased after glucose alone, was unchanged after egg white ingestion, and was greatest after ingestion of gelatin. The free fatty acid concentration decrease was 4- to 8-fold greater after the ingestion of protein with glucose compared with ingestion of glucose alone.     

The metabolic response to ingestion of proline with and without glucose

Ingested protein results in an increase in circulating insulin and glucagon concentrations and no change, or a slight decrease, in circulating glucose. In subjects with type 2 diabetes, when protein is ingested with glucose, insulin is further increased and the glucose rise is less than when glucose is ingested alone. Presumably these effects are due to the amino acids present in the proteins. The effects of individual amino acids, ingested in physiologic amounts, with or without glucose, have not been determined. Therefore, we have begun a systematic study of the response to ingested amino acids. Eight young, non-obese, subjects (4 men, 4 women) ingested 1 mmol proline/kg lean body mass, 25 g glucose, 25 g glucose + 1 mmol proline/kg lean body mass or water only on 4 separate occasions at 8 am. Blood was obtained before and after ingestion of the test meal over the following 150 minutes. Proline ingestion resulted in a 13-fold increase in the plasma proline concentration. This was decreased by 50% when glucose was ingested with proline. Proline alone had little effect on glucose, insulin, or glucagon concentrations. However, ingestion of proline with glucose resulted in a 23% attenuation of the glucose area response and no change in insulin response compared with the response to that of glucose alone. A glucose-stimulated decrease in glucagon was further facilitated by proline. Ingested proline is readily absorbed. It reduces the glucose-induced increase in glucose concentration in the presence of an unchanged insulin and a decreased glucagon response.     

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.     

Leucine, when ingested with glucose, synergistically stimulates insulin secretion and lowers blood glucose

Our laboratory is interested in the metabolic effects of ingested proteins. As part of this research, we currently are investigating the metabolic effects of ingested individual amino acids. The objective of the current study was to determine whether leucine stimulates insulin and/or glucagon secretion and whether, when it is ingested with glucose, it modifies the glucose, insulin, or glucagon response. Thirteen healthy subjects (6 men and 7 women) were studied on 4 different occasions. Subjects were admitted to the special diagnostic and treatment unit after a 12-hour fast. They received test meals at 8:00 am. On the first occasion, they received water only. Thereafter, they received 25 g glucose or 1 mmol/kg lean body mass leucine or 1 mmol/kg lean body mass leucine plus 25 g glucose in random order. Serum leucine, glucose, insulin, glucagon, and α-amino nitrogen concentrations were measured at various times during a 2.5-hour period after ingestion of the test meal. The amount of leucine provided was equivalent to that present in a high-protein meal, that is, that approximately present in a 350-g steak. After leucine ingestion, the leucine concentration increased 7-fold; and the α-amino nitrogen concentration increased by 16%. Ingested leucine did not affect the serum glucose concentration. When leucine was ingested with glucose, it reduced the 2.5-hour glucose area response by 50%. Leucine, when ingested alone, increased the serum insulin area response modestly. However, it increased the insulin area response to glucose by an additional 66%; that is, it almost doubled the response. Ingested leucine stimulated an increase in glucagon. Ingested glucose decreased it. When ingested together, the net effect was essentially no change in glucagon area. In summary, leucine at a dose equivalent to that present in a high-protein meal, had little effect on serum glucose or insulin concentrations but did increase the glucagon concentration. When leucine was ingested with glucose, it attenuated the serum glucose response and strongly stimulated additional insulin secretion. Leucine also attenuated the decrease in glucagon expected when glucose alone is ingested. The data suggest that a rise in glucose concentration is necessary for leucine to stimulate significant insulin secretion. This in turn reduces the glucose response to ingested glucose.     

Metabolism in sea raven (Hemitripterus americanus) hepatocytes: the effects of insulin and glucagon

The metabolism of the sea raven, Hemitripterus americanus, hepatocyte preparation was studied, emphasizing the roles of insulin and glucagon on carbohydrate status. Sea raven hepatocyte glycogen was depleted throughout the preincubation and 2-hr incubation period in the presence of either glucose or serine. Bovine glucagon stimulated glycogen loss and increased glucose levels and serine flux to glucose. Porcine insulin prevented glycogen depletion at least over 1.5 hr of incubation, but did not affect glucose levels in the hepatocytes. It also significantly increased serine flux to glucose, glycogen, and protein, and alanine flux to glucose, CO2, and protein. Teleost insulin did not alter the pattern of hepatic glycogen depletion, while it did increase glucose levels and serine flux to glucose, glycogen, and lipids, and alanine flux to CO2 and glucose. Both glucagon and porcine insulin increased glucose flux to glycogen, but neither altered glucose conversion to CO2, lactate, or protein. The teleost insulin had no effect on glucose conversion to any product tested. Teleost insulin had an additive effect on the glucagon-induced increases in total glucose production and gluconeogenesis from serine, while glucagon offset the insulin stimulation of serine flux to glycogen and CO2. The results demonstrate that glucagon functions to increase glucose production from gluconeogenic precursors and glycogen in sea raven hepatocytes, while insulin demonstrates anabolic effects through gluconeogenic precursors. It is suggested that insulin functions in sea raven hepatocytes to increase glycogen stores through increased amino acid utilization and/or to increase glucose production for transport to, and storage in, glucose-utilizing tissues (e.g., muscle). An antagonism between insulin and glucagon on the glycolytic/gluconeogenic pathways as is found in mammalian livers is not as clear in sea raven hepatocytes. These findings are consistent with the carnivorous diet of the sea raven and a preferentially gluconeogenic role for the liver of this species.     

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.     

Metabolic response to cottage cheese or egg white protein, with or without glucose, in type II diabetic subjects.

Test meals with 25 g protein in the form of cottage cheese or egg white were given with or without 50 g glucose to male subjects with mild to moderately severe, untreated, type II diabetes. Water was given as a control meal. The glucose, insulin, C-peptide, alpha amino nitrogen (AAN), glucagon, plasma urea nitrogen (PUN), nonesterified fatty acid (NEFA), and triglyceride area responses were determined using the water meal as a baseline. The glucose area responses following ingestion of cottage cheese or egg white were very small compared with those of the glucose meal, and were not significantly different from one another. The serum insulin area response was 3.6-fold greater following ingestion of cottage cheese compared with egg white (309 v 86 pmol/L.h). The simultaneous ingestion of glucose with cottage cheese or egg white protein decreased the glucose area response to glucose by 11% and 20%, respectively. When either protein was ingested with glucose, the insulin area response was greater than the sum of the individual responses, indicating a synergistic effect (glucose alone, 732 pmol/L.h; glucose with cottage cheese, 1,637 pmol/L.h; glucose with egg white, 1,213 pmol/L.h). The C-peptide area response was similar to the insulin area response. The AAN area response was approximately twofold greater following ingestion of cottage cheese compared with egg white. Following ingestion of glucose, it was negative. When protein was ingested with glucose, the AAN area responses were additive. The glucagon area response was similar following ingestion of cottage cheese or egg white protein. Following glucose ingestion, the glucagon area response was negative.(ABSTRACT TRUNCATED AT 250 WORDS)     

Amino acid disturbances in type III glycogenosis: differences from type I glycogenosis

The plasma glucose, insulin, glucagon, lactate and amino acid response patterns to glucose and protein meals were examined in 11 patients with type III glycogen storage disease (GSD-III). The amino acid metabolism in GSD-III was shown to differ from that observed in normal subjects and in type I glycogen storage disease (GSD-I) patients. The outstanding findings involved the principal gluconeogenic amino acid, alanine. Postabsorptive levels of alanine in GSD-III were significantly below those of normal controls. Following glucose ingestion, alanine rose markedly in GSD-III, which differed from normal subjects in whom no change occurred, and from GSD-I patients in whom a sharp fall was observed. Following beef ingestion, the direction of change of alanine was similar in the three groups, but the circulating levels in GSD-III were significantly less than those observed in GSD-I and normal controls. The possibility that gluconeogenesis is enhanced in GSD-III was supported by the prompt rise in blood glucose observed following beef ingestion, which differed from GSD-I and normal subjects, in which no rise in glucose was observed.     

Stimulation of hepatic glycogen synthesis by amino acids.

Hepatocytes isolated from livers of fasted rats form little glycogen from glucose or lactate at concentrations below 20 mM. Glycogen is formed in substantial quantities at a glucose concentration of 60 mM. In the presence of 10 mM glucose, 20-30% as much glycogen as glucose is formed from fructose, sorbitol, or dihydroxyacetone. The addition of either glutamine, alanine, or asparagine stimulates the formation of glycogen from lactate 10- to 40-fold. The formation of glucose and glycogen is then about equal, and glycogen deposition in hepatocytes is similar to rates attained in vivo after fasted rats are refed. The amino acids stimulate 1.5- to 2-fold glycogen synthesis from fructose, and 2- to 4-fold synthesis from dihyDROXYACETONE. Ammonium chloride is about one-half as effective as amino acids in stimulating glycogen synthesis when glucose with lactate are substrates. It increased glycogen synthesis 25-50% from fructose but inhibited synthesis from dihydroxyacetone plus glucose.     

Insulin and the regulation of glycogen metabolism and gluconeogenesis in American eel hepatocytes

The regulation of glycogenolysis and alanine and lactate gluconeogenesis, glycogenesis, and oxidation by porcine insulin was studied in isolated American eel hepatocytes. Experiments were performed in the summer, winter, and spring using naturally fluctuating water temperatures to establish the seasonal dependence of these processes and their hormone sensitivities. Porcine insulin (10(-8) M) maintained glycogen content, decreased total glucose production, increased lactate and alanine flux to glycogen in hepatocytes from summer and winter eels, and had a small stimulatory effect on alanine gluconeogenesis in the spring. The hormone counteracted bovine glucagon-stimulated glycogen depletion and glucose production, but only offset the glucagon effect on gluconeogenesis when glycogen content was below summer values. Effects of the two hormones on oxidation were additive in the summer, but were equivocal at other seasons. The magnitudes of the hormone effects on metabolism were generally smaller in the winter than in the other seasons. Anglerfish glucagon (10(-8) M) effects, studied in the spring, mimicked those of bovine glucagon. Porcine insulin effects in the presence of anglerfish glucagon were the same as in the presence of bovine glucagon. These studies generally support the antagonistic role between insulin and glucagon and the insulin-stimulated C3 precursor flux to glycogen reported in mammalian hepatocytes. Although these metabolic processes are seasonally adjusted, the precise mechanism involved is not understood.     

Contribution of galactose and fructose to glucose homeostasis

To determine the contributions of galactose and fructose to glucose formation, 6 subjects (26 ± 2 years old; body mass index, 22.4 ± 0.2 kg/m²) (mean ± SE) were studied during fasting conditions. Three subjects received a primed constant intravenous infusion of [6,6-²H₂]glucose for 3 hours followed by oral bolus ingestion of galactose labeled to 2% with [U-¹³C]galactose (0.72 g/kg); the other 3 subjects received a primed constant intravenous infusion of [6,6-²H₂]glucose followed by either a bolus ingestion of fructose alone (0.72 g/kg) (labeled to 2% with [U-¹³C]fructose) or coingestion of fructose (labeled with [U-¹³C]fructose) (0.72 g/kg) and unlabeled glucose (0.72 g/kg). Four hours after ingestion, subjects received 1 mg of glucagon intravenously to stimulate glycogenolysis. When galactose was ingested alone, the area under the curve (AUC) of [¹³C₆]glucose and [¹³C₃]glucose was 7.28 ± 0.39 and 3.52 ± 0.05 mmol/L per 4 hours, respectively. When [U-¹³C]fructose was ingested with unlabeled fructose or unlabeled fructose plus glucose, no [¹³C₆]glucose was detected in plasma. The AUC of [¹³C₃]glucose after fructose and fructose plus glucose ingestion was 20.21 ± 2.41 and 6.25 ± 0.34 mmol/L per 4 hours, respectively. Comparing the AUC for the ¹³C₃ vs ¹³C₆ enrichments, 67% of oral galactose enters the systemic circulation via a direct route and 33% via an indirect route. In contrast, fructose only enters the systemic circulation via the indirect route. Finally, when ingested alone, fructose and galactose contribute little to glycogen synthesis. After the coingestion of fructose and glucose with the resultant insulin response from the glucose, fructose is a significant contributor to glycogen synthesis.     

Carbohydrate metabolism in pregnancy. XIV. Relationships between circulating glucagon,insulin, glucose and amino acids in response to a “mixed meal” in late pregnancy

Gestational influences upon the changes in circulating glucose, amino acids, insulin, and glucagon after the ingestion of a “mixed meal” containing carbohydrate (50 g), protein (25 g), and fat (10 g) were examined. Nine subjects were tested during weeks 30–40 of gestation and again 6–8 wk postpartum. The “mixed meal” elicited greater and more prolonged increases in plasma glucose antepartum, whereas the increments in total serum amino acids were blunted at all time points. In the face of greater glycemic but lesser aminogenic stimulation, the integrated increase in plasma insulin was 60% greater antepartum than post partum, whereas the increment in glucagon was not significantly altered. Thus, integrated insulin/glucagon response was increased during antepartum studies. The insulin preponderance following alimentary challenge with mixed nutrients would suggest that the anabolism of ingested amino acids is “facilitated” during late human pregnancy.     

Effect of buformin on splanchnic carbohydrate and substrate metabolism in healthy man

The effect of buformin (100 mg b.i.d. for 5 days) on carbohydrate metabolism, both splanchnic glucose output (SGO) and net substrate exchange were studied in 6 healthy male volunteers in the basal state and following glucose ingestion (100 g). Control studies without buformin were also performed in 5 men. Splanchnic glucose and substrate exchange was determined by means of the hepatic venous catheter technique. SGO was 154 ± 18 (SEM) mg/min in the postabsorptive state and increased 33.3 ± 2.8 g above the basal level during the 150 min period following glucose ingestion. Buformin administration did not alter basal SGO (157 ± 26 mg/min), nor the splanchnic exchange of pyruvate, alanine, glycerol, OH-butyrate and acetoacetate. Splanchnic lactate balance was altered by buformin and net lactate output occurred. Following glucose ingestion the rise in splanchnic lactate output was increased, whereas no change in SGO ($\text{32.9 ± 3.5 g}\text{150 min}$) and splanchnic exchange of the other substrates was observed. The increase in arterial blood glucose concentration following oral glucose loading was reduced by buformin pretreatment (p < 0.0005). The insulin production rate (basal, 16 ± 2 mU/min; following oral glucose, $\text{13 ± 2 U}\text{150 min}$) as calculated from C-peptide release from the splanchnic area was unchanged by buformin. Except for a marked rise in splanchnic lactate production, buformin did not alter splanchnic carbohydrate metabolism after orally ingested glucose in healthy man. The diminished increase in arterial blood glucose concentration associated with unaltered insulin production suggests that buformin facilitates glucose utilization by peripheral tissues.     

The 75-g oral glucose tolerance test: Effect on splanchnic metabolism of substrates and pancreatic hormone release in healthy man

To determine the effect of the 75 g oral glucose tolerance test on carbohydrate and lipid metabolism, the splanchnic exchange of glucose, lactate, pyruvate, non-esterified fatty acids, beta-hydroxybutyrate and acetoacetate as well as the release of insulin, C-peptide, glucagon and pancreatic polypeptide were evaluated in eight healthy male volunteers in the basal state and for 150 min following glucose ingestion. Oral glucose loading was followed by a rapid rise in splanchnic output of glucose (mean +/- SEM; 154 +/- 12 mmol/150 min), pyruvate (1.2 +/- 1.2 mmol/150 min) and lactate (8.6 +/- 2.0 mmol/150 min), whereas there were reductions in the splanchnic uptake of non-esterified fatty acids (-10.7 +/- 4.4 mmol/150 min) and the splanchnic output of beta-hydroxybutyrate (-4.8 +/- 3.3 mmol/150 min) and acetoacetate (-3.0 +/- 1.2 mmol/150 min). In parallel, splanchnic output of insulin (12.3 +/- 2.7 nmol/150 min), C-peptide (36.1 +/- 5.0 nmol/150 min) and transiently of pancreatic polypeptide rose, whereas that of glucagon fell (-0.58 +/- 0.21 nmol/150 min). Even at 150 min after glucose ingestion, splanchnic output and arterial concentrations of glucose, lactate, insulin and C-peptide were still above their respective basal values while those of non-esterified fatty acids and glucagon were reduced. Taking into account the partial suppression of endogenous glucose production by ingested glucose it is concluded that, in normal postabsortive man, only 49-63% of a 75 g oral glucose load is retained by the splanchnic bed during the first 150 min, the rest being available for non-hepatic tissues.(ABSTRACT TRUNCATED AT 250 WORDS)     

Amino acid and glucose metabolism in the postabsorptive state and following amino acid ingestion in the dog

Amino acid and glucose metabolism was studied in nine awake 18-hour fasted dogs with chronic portal, arterial, and hepatic venous catheters before and for three hours after oral ingestion of amino acids. The meal was composed of a crystalline mixture of free amino acid, containing neither carbohydrate nor lipid. Following the amino acid meal, plasma glucose concentration declined slowly and this occurred despite a rise in hepatic glucose release. Portal plasma insulin rose transiently (30 +/- 7 to 50 +/- 11 microU/mL, P less than 0.05) while the increase in portal glucagon was more striking and persisted throughout the study (162 +/- 40 to 412 +/- 166 pg/mL). Over the three hours following amino acid ingestion, the entire ingested load of glycine, serine, phenylalanine, proline, and threonine was recovered in portal blood as was 80% of the ingested branched chain amino acids (BCAA). The subsequent uptake of these glucogenic amino acids by the liver was equivalent to the amount ingested, while hepatic removal of BCAA could account for disposal of 44% of the BCAA absorbed; the remainder was released by the splanchnic bed. During this time, ongoing gut production of alanine was observed and the liver removed 1,740 +/- 170 mumol/kg of alanine, which was twofold greater than combined gut output of absorbed and synthesized alanine. In the postcibal state, the total net flux of alanine and five other glucogenic amino acids from peripheral to splanchnic tissues (1,480 mumol/kg 3 h) exceeded the net movement of branched chain amino acids from splanchnic to peripheral tissues (590 mumol/kg/3 h).(ABSTRACT TRUNCATED AT 250 WORDS)     

A comparison of adrenalin and glucagon effects on carbohydrate levels of larval and adult Rana pipiens.

Hyperglycemia was observed in frogs after single ip injections of doses above 50 μg/kg of adrenalin and glucagon. Blood glucose responses were maximal at 3 hr and lasted at least 5 hr. Lactacidemia was apparent after treatment with adrenalin at doses of 50 μg/kg and above. The increase in lactate was apparent by 1 hr and had dropped to control levels by 5 hr. Tissue glycogen loss was not observed after treatment with either hormone in adults. Preliminary studies with tadpoles indicated a hyperglycemic response to adrenalin and glucagon at doses of 1.0 mg/kg and an increase in lactate after injection of a 1.0 mg/kg dose of adrenalin. Liver glycogen loss was observed following glucagon but not adrenalin. Both hormones stimulated glucose release from liver slices of frogs and tadpoles.