Effect of pectin on gastric emptying and gastroduodenal motility in normal subjects

The effects of pectin ingestion on gastric emptying, gastroduodenal motility, and plasma levels of glucose, insulin, and glucagon were studied. Initial studies demonstrated that 15 g of pectin was the optimal dose. Subsequently 6 healthy male volunteers were studied on 4 separate days at random. On day 1, gastric emptying of a liquid and a solid meal was assessed by radioisotope technique using 99mTc-dithiopropylthiomine. On day 2, the gastric emptying study was repeated with the addition of pectin to each meal. Plasma levels of glucose, insulin, and glucagon also were determined during these 2 days. On day 3, the effects of liquid and solid meals on gastroduodenal motility were assessed by means of a perfused catheter system. On day 4, the motility study was repeated with the addition of pectin to each meal. Pectin supplementation caused a significant prolongation of gastric emptying half-time of both liquid and solid meals (p less than 0.05). The addition of pectin, however, did not have any significant effect on gastroduodenal motility other than increasing the duodenal motility index 10 min after the liquid meal. The addition of pectin to the liquid meal lowered plasma levels of insulin at 15, 30, and 45 min, and glucagon levels 15 min after the meal. No effect was noted on blood sugar levels. On the other hand, the addition of pectin to the solid meal had no effect on plasma levels of glucose, insulin, and glucagon. We conclude that pectin supplementation delays gastric emptying of both liquid and solid meals in normal human subjects without causing notable changes in gastroduodenal motility or significant variations in pancreatic hormone plasma levels. The pectin effect on gastric emptying may be caused solely by increasing the viscosity of the meals.     

Metabolic interactions of glucagon and cortisol in man--studies with somatostatin

The metabolic response to pathophysiologic concentrations of glucagon, induced by glucagon infusion, has been examined in normal man before and after 36-60 hr hypercortisolaemia, induced by administration of tetracosactrin-depot. Glucagon alone increased serum insulin levels twofold but blood glucose was unaltered. Plasma NEFA and blood ketone body concentrations were decreased by glucagon infusion. Tetracosactrin produced a threefold rise in serum cortisol levels and caused mild fasting hyperglycemia and hyperinsulinaemia. Subsequent glucagon infusion had no effect on circulating insulin, glucose, NEFA or ketone body concentrations. Simultaneous infusion of somatostatin, to produce partial insulin-deficiency, unmasked a hyperglycemic action of glucagon (+ 3.8 +/- 0.2 mmol/l at 90 min, p less than 0.02). This glucagon-induced rise in blood glucose was diminished by prior tetracosactrin administration. Tetracosactrin revealed a mild lipolytic action of glucagon in partial insulin deficiency, not apparent in the euadrenal state. Glucagon was equally hyperketonemic during somatostatin infusion before and after tetracosactrin. Thus the hyperglycemic and hyperketonemic actions of glucagon at pathophysiologic levels are restricted to insulin deficiency. Hypercortisolaemia reveals a lipolytic action of glucagon in insulin-deficient man but does not potentiate the hyperglycemic or hyperketonemic effects.     

Lowering of fasting and food stimulated serum immunoreactive gastric inhibitory polypeptide (GIP) by glucagon.

The effect of intravenous glucagon infusion on serum levels of immunoreactive GIP (IR-GIP), insulin (IRI), gastrin (IRG), and on blood glucose has been investigated in six healthy volunteers in the fasting state and during ingestion of a mixed standard meal. Glucagon (500 ng/kg/min) lowered significantly serum levels of IR-GIP and IRG below the fasting values and increased the levels of IRI and blood glucose. Glucagon (50 ng/kg/min) infused 30 minutes before and continued 90 minutes after ingestion of a test meal abolished the IR-GIP response, suppressed significantly the IRG response, and left the IRI response unchanged. The same glucagon dose infused 60 minutes after ingestion of the test meal decreased significantly the raised levels of IR-GIP and IRG to fasting levels without changing IRI values. It is concluded that exogenous glucagon inhibits Gip release at the level of the GIP-producing cells.     

Glycemic response during exercise after administration of insulin lispro compared with that after administration of regular human insulin

To examine the glycemic response during exercise after administration of short-acting insulin lispro, we compared changes in plasma glucose concentrations during exercise performed by patients with diabetes after the administration of either insulin lispro or regular human insulin. Seven patients with diabetes (two with type 1 and five with type 2) participated in this study. Each of the insulin-depleted subjects received the same number of units of either insulin lispro or regular human insulin, delivered subcutaneously to the abdomen. The next day, each subject received a similar injection of the solution not previously administered. After each injection, the subjects were fed a standard meal of approximately 9 kcal/kg body weight. One hour after eating the test meal, the subjects performed 30 min of cycle ergometer exercise at 50% maximal oxygen uptake. Plasma glucose, insulin, glucagon, growth hormone (GH), and catecholamine concentrations were then measured at specific intervals. Insulin concentrations were higher and peaked earlier after administration of insulin lispro than after administration of regular human insulin. The length of time, needed to reach minimum plasma glucose concentration after exercise was begun, was significantly shorter after administration of insulin lispro, and the percentage of plasma glucose decrease induced by exercise relative to the peak concentration was significantly greater. No differences were found in the concentration changes of counterregulatory hormones between the insulin lispro data and the regular human insulin data. Compared with regular human insulin, insulin lispro induces a more rapid and greater decrease in plasma glucose concentration during exercise because of its faster absorption.     

Plasma insulin and glucagon after ingestion of meal enriched with increased doses of pectin in healthy man

The effects of three doses of pectin (5, 10 and 15 g) included in a solid-liquid meal on the postprandial plasma insulin and glucagon responses were studied in 12 healthy men. The mean plasma glucagon level was significantly smaller with 5 g of pectin than the control values at 150 min (p less than 0.05) whereas plasma insulin values did not vary. No change in mean plasma glucagon and insulin levels was noted with 10 g and 15 g of pectin although the mean blood glucose levels were significantly higher than the control values at 180 min (p less than 0.05). Addition of pectin to a meal, even if the doses were relatively important, had little or no effect on the postprandial hormonal responses in healthy men. However, pectin could be of renewed interest because of the possibility of its action of satiety by means of sustained late blood glucose levels.     

Effect of indomethacin on the metabolic and hormonal response to a standardized breakfast in normal subjects

Summary We have investigated the influence of a single oral administration of indomethacin on blood glucose, plasma free fatty acids (FFA), -amino-nitrogen, insulin and glucagon concentrations in young healthy subjects. Two groups of 6 subjects were studied, the first received a standardized 500 kcal mixed meal without any previous drug administration (controls) whereas the second group received 50 mg indomethacin 2 h before ingesting an identical meal. Plasma indomethacin concentration reached its maximum (2.36±0.36 g/ml) 15 min after administration and declined to 0.45±0.04 ug/ml after 2 h. Indomethacin ingestion was followed by a significant increase in blood glucose and plasma FFA reaching their maximum value at 45 min and returning to basal levels at 120 min. No simultaneous changes in plasma -amino-nitrogen, insulin or glucagon levels were detected during this period. The meal was followed by a rise in blood glucose and plasma insulin as well as by a decrease in plasma FFA concentration. No significant differences were detected between the controls and the subjects receiving indomethacin. In controls, the meal was followed by a rise in plasma -amino-nitrogen and a modest although significant increase in glucagon levels. In indomethacin-treated subjects, the increment of -amino-nitrogen was less marked and the increase in plasma glucagon was not observed. Thus, indomethacin by itself can exert several metabolic effects; however, it does not deteriorate the blood glucose or insulin profile after a regular meal. The present work is the first to demonstrate that an inhibitor of prostaglandin synthesis inhibits the plasma glucagon rise occurring after a physiological stimulus such as a normal meal. On the basis of previousin vitro experiments, we suggest that this effect results from an inhibition of glucagon secretion by the PG synthesis inhibitor.     

Exendin-4 normalized postcibal glycemic excursions in type 1 diabetes

Exendin-4 is a reptilian peptide that activates the mammalian receptor for truncated glucagon-like peptide 1 (tGLP-1) with relatively prolonged actions. Exendin-4 and tGLP-1 can reduce blood glucose levels by stimulating insulin secretion, inhibiting glucagon secretion, and delaying gastric emptying. We tested a range of doses of exendin-4 on postcibal glycemic excursions in nine volunteers with type 1 diabetes, all with negligible endogenous insulin secretion, in paired comparisons with vehicle in at least six volunteers with each of six doses. We established a side effect-free dose and an appropriate antecibal time for sc administration of exendin-4. Subsequently, exendin-4 was administered 15 min before breakfast, with usual insulin, to eight of the volunteers. Acetaminophen was ingested with the meal as an indicator of gastric emptying. The mean plasma glucose excursion was reduced by 90%, falling into the normal range, after breakfast, whereas plasma pancreatic polypeptide, glucagon, and acetaminophen levels were reduced, and insulin levels were not affected. Thus, normalization of postcibal glycemia was associated with delayed gastric emptying and suppression of glucagon secretion, without increased secretion or blood levels of insulin. We suggest that tGLP-1 agonists have therapeutic potential as congeners with insulin in C-peptide-negative type 1 diabetes.     

The effect of ingestion of meat on hepatic extraction of insulin and glucagon and hepatic glucose output in conscious dogs

The effect of ingestion of protein on hepatic extraction of insulin and glucagon and hepatic glucose output were investigated in conscious dogs. The ingestion of meat stimulated both insulin and glucagon secretion but the glucagon response was much more rapid and greater than that of insulin. Secretion of glucagon demonstrated a biphasic pattern while insulin release was monophasic. The fractional hepatic extraction of glucagon increased gradually from the basal value of 15 +/- 3% to a peak of 36 +/- 5% at 90 min, and that of insulin increased from the basal level of 41 +/- 2% to 54 +/- 4% at 45 and 60 min. The increased hepatic extraction of glucagon and insulin after meat ingestion may be explained by neural or hormonal signals from the gut. The blood glucose and hepatic glucose output did not increase significantly despite the significant decrease of the portal vein insulin to glucagon molar ratio as well as the significant decrease of the molar ratio of the hepatic uptake of these hormones. The absence of greater hepatic glucose production despite the augmented glucagon secretion and decreased portal vein insulin to glucagon molar ratio could reflect down regulation by glucagon.     

Post-prandial glucose excursions following four methods of bolus insulin administration in subjects with type 1 diabetes.

AIMS: To determine if one method of short-acting insulin bolus administration is superior to other methods in managing a meal high in carbohydrates, calories and fat. METHODS: Nine subjects receiving continuous subcutaneous insulin infusion using insulin lispro (Humalog) agreed to consume the same meal high in carbohydrates, calories and fat on four occasions 1 week apart. They received the same dose of bolus insulin on each of the four occasions randomly assigned and beginning 10 min prior to the meal as either a single bolus, two separate boluses of one-half the same total dose (the second after 90 min), the entire bolus given as a square-wave (over 2 h) or a dual-wave (70% as a bolus and 30% as a square-wave over 2 h). Blood glucose levels were measured at -60 and -30 min and at zero time, and then every half-hour for 6 h using the Hemacue in the out-patient clinic. RESULTS: Changes in blood glucose values from fasting were the lowest after 90 and 120 min (P < 0.01) when the dual wave was administered. When the dual or square-wave methods of insulin administration were used, subjects had significantly lower glucose levels after 4 h in comparison with when the single or double boluses were used (P = 0.04). CONCLUSIONS: We conclude that the dual wave provided the most effective method of insulin administration for this meal. The dual- and square-wave therapies resulted in lower glucose levels 4 h after the meal in comparison with the single and double-bolus treatments.     

GLUCAGON AND DIABETES

In order to determine whether glucagon levels of diabetic subjects are suppressible, alpha cell responsiveness to acute insulin administration (0.1 units/kg intravenously) was determined in fourteen juvenile onset, healthy diabetic and eight control subjects. In the diabetics, insulin produced a significant but slow fall in blood glucose over 60 min (P<0.01). On the other hand, glucagon levels fell dramatically in all diabetics to undetectable levels (P<0.001). Only one diabetic became hypoglycaemic and he alone showed a rebound rise of glucagon at 60 min. The rate of fall of blood glucose in the diabetic subjects was not influenced by the basal glucagon level (r= 0.13) or the rate of fall of plasma glucagon (r= 0.04). The glucose and glucagon responses of control subjects to insulin administration were in sharp contrast to the diabetics: blood glucose levels fell rapidly to hypoglycaemic levels and were associated with a major rise in glucagon levels (mean rise 116 pmol/1, P<0.001). We conclude that alpha cell hyperfunction in human diabetes can be completely suppressed by insulin administrtion and is therefore not autonomous, and that the slow rate of fall of blood glucose following insulin administration in diabetics is not secondary to glucagon excess.     

Effect of intravenously administered glucose on glucagon and insulin secretion during fat absorption

The intravenous infusion of glucose was found to alter profoundly the response of insulin and glucagon to an intraduodenally administered fat meal in conscious dogs from that of dogs given only intravenous saline as a control. In the latter, insulin rose only 4 μU/ml and glucagon rose from 142 SEM ± 8 to a peak of 221 pg/ml SEM ± 50. When glucose was infused, raising plasma glucose above $\text{170 mg}\text{100 ml}$, the administration of fat was associated with a rise in mean insulin to 344 μU/ml, and glucagon remained suppressed by hyperglycemia to below baseline levels, despite the fat meal. The peak insulin response to a fat meal plus glucose infusion was more than three times the peak level observed when glucose was infused alone without a meal or with a nonabsorbable intraduodenal volume load in the form of mineral oil. This suggests that the absorption of fat elicits an entero-insular signal that is greatly potentiated by exogenous glucose. These glucose-induced changes in the hormonal response to a fat meal may mediate certain of the metabolic effects of carbohydrates.     

A supplementary infusion of glucose-dependent insulinotropic polypeptide (GIP) with a meal does not significantly improve the beta cell response or glucose tolerance in type 2 diabetes mellitus

Newly diagnosed, previously untreated patients with type 2 diabetes mellitus (n = 6) were studied on two separate days after overnight fasts. On each day they were given a 500-kcal mixed meal plus an infusion of either porcine glucose-dependent insulinotropic polypeptide (GIP) (0.75 pmol/kg/min) or control solution (CS) from 0 to 30 min in random order. Frequent measurements of plasma glucose, C-peptide, insulin and GIP concentrations were made. Fasting GIP levels were similar on both days. During the meal plus GIP infusion plasma GIP levels increased from a basal value of 7.6 +/- 1.5 pmol/1 to a peak of 88.6 +/- 5.4 pmol/1 at 30 min. Following the meal infusion of CS GIP increased from a fasting level of 10.3 +/- 1.2 pmol/1 to a significantly lower peak of 58.0 +/- 8.3 pmol/1 at 60 min. During the meal plus GIP infusion GIP levels were higher at 10-45 min and at 90 min (P less than 0.05-0.001). Fasting and postprandial glucose, C-peptide and insulin levels were, however, similar on both study day. A supplementary infusion of porcine GIP with a mixed meal did not significantly alter the beta cell response or glucose tolerance in this group of patients with type 2 diabetes mellitus.     

The mechanism of the effect of oxytocin on plasma concentrations of glucose, insulin and glucagon in conscious dogs

Injections and infusions of oxytocin into conscious dogs caused an increase in plasma concentrations of glucose, insulin and glucagon. When blood glucose was clamped at a raised level the injection of oxytocin still increased insulin and glucagon concentrations in plasma. Infusion of somatostatin suppressed plasma concentrations of glucagon and insulin but did not prevent oxytocin-induced increments in blood glucose. Injection of oxytocin still caused a marked release of glucagon, whereas the insulin response was greatly diminished. When endogenous insulin and glucagon secretion was suppressed by infusion of somatostatin and glucose levels were stabilized by concomitant infusions of glucagon and insulin, injections of oxytocin did not alter blood glucose concentrations. It is concluded that the increase in blood glucose following the administration of oxytocin is secondary to the release of glucagon and that oxytocin exerts a direct stimulatory effect on glucagon and possibly insulin secretion.     

Response of plasma glicentin to intraduodenal administration of glucose in piglets

Controversial results concerning the secretion of glicentin prompted us to investigate the response of circulating glicentin to intraduodenal administration of glucose in piglets. A 20% solution of glucose (2 g/kg) was administered into the duodenum of six piglets in a fully conscious state. As blood glucose rose, plasma insulin increased to a peak of 21 +/- 4 microU/ml. Plasma glucagon, determined by C-terminal-specific antiserum, was 70 +/- 30 pg/ml at fasting and slightly increased after the glucose load. Plasma immunoreactive glucagon measured by cross-reacting glucagon antiserum increased from the baseline of 1563 +/- 260 to a peak of 4738 +/- 415 pg/ml at 120 min. Plasma glicentin determined by antiserum R 64 was 463 +/- 81 pmol/l at baseline and reached a peak level of 1081 +/- 174 pmol/l at 90 min. The percent changes of plasma glucagon from the fasting level measured by cross-reacting antiserum and glicentin were 296 and 233%, respectively. There was a significant correlation between plasma glucagon measured by cross-reacting antiserum and glicentin (r = 0.817, P less than 0.001). Chromatography of plasma obtained during glucose load revealed the heterogeneity of glicentin. It can be concluded from the present study that glicentin is clearly secreted in response to intraluminal administration of glucose.     

Effect of alpha-1-blockade by prazosin on blood sugar, insulin and glucagon levels in normals and non-insulin dependent diabetics

The AA. studied the glycometabolic activity of prazosin, a hypotensive drug with an adrenergic blocking activity of alpha-1-selective type. Twenty-two moderately hypertensive subjects were studied. Their ages ranged from 37 to 57 years; 10 of the patients had non-insulin dependent diabetes mellitus. After overnight fasting every patient underwent an oral glucose test (g 100) at 09:00. Blood samples were withdrawn at 0, 30, 60, 90 and 120 minutes. Each patient was then given in randomized and double-blind fashion placebo or prazosin (4 mg, 2 pills of Minipress Pfizer per day) for the following 7 days; then another glucose load was administered. Glucose (enzymatic method), insulin and glucagon (RIA method) were measured in each blood sample. In non diabetic subjects glucose levels (60, 90, 120 min and total area) after oral glucose and prazosin were statistically higher (p less than 0.05, p less than 0.01, p less than 0.05) than after glucose only. No significant difference between the two curves was observed in the diabetic group. IRI levels in normal subjects were statistically higher after 120 min and in the total area, while no evident changes were noted in the diabetic group. The glucagon curve seen after oral glucose was not modified by prazosin in either group.     

The intra-nasal administration of insulin induces significant hypoglycaemia and classical counterregulatory hormonal responses in normal man

The present study aimed at investigating the metabolic and hormonal consequences of intra-nasal administration of insulin in normal man. Lyophylisated regular porcine insulin (Insuline Ordinaire Organon) diluted with a non ionic detergent (Laureth-9 0,25%) was administered intra-nasally in 8 overnight fasted healthy volunteers using a calibrated aerosol delivery device (90 microliters = 9 U of insulin/spray) up to a total insulin dose close to 1 U/kg body weight. After intra-nasal insulin administration, plasma insulin levels rose from 5 +/- 1 to 38 +/- 10 mU/l (2p less than 0.01) at min 15, blood glucose concentrations decreased from 4.4 +/- 0.2 to 3.2 +/- 0.3 mmol/l (2p less than 0.01) at min 45, plasma C-peptide levels diminished from 327 +/- 31 to 174 +/- 28 mumol/l (2p less than 0.01) at min 60 and plasma free fatty acids concentrations fell from 336 +/- 109 to 130 +/- 31 mumol/l (2p less than 0.05) at min 30. The fall in blood glucose resulted in a prompt increase in plasma glucagon levels (from 78 +/- 28 to 150 +/- 24 ng/l at min 45; 2p less than 0.05) and in later rises in plasma growth hormone and cortisol concentrations. There was a close relationship between the individual maximal decreases in blood glucose levels and the individual maximal increases in plasma insulin (r = 0.81), glucagon (r = 0.88), cortisol (r = 0.87) and growth hormone (r = 0.76) concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Metabolic and endocrine responses to a standard mixed meal. A physiologic study

Summary In order to study endocrine and metabolic responses to normal food ingestion, 8 ‘healthy’ subjects received a standard mixed meal which reflected the composition of Western diet (CHO 47%, protein 23%, fat 26%, alcohol 4%), in 20 min. Before and after the meal, in each subject glucose, lactate, FFA, insulin, C-peptide, glucagon and HGH were determined. The results showed that glycemic and insulinemic responses were not very different from those observed after the classical oral glucose tolerance test. Plasma FFA and blood lactate decreased progressively after the meal. Plasma glucagon and HGH showed opposite changes: pancreatic glucagon rose and HGH slightly declined after composite food ingestion. Supported by C.N.R. grant No. 76.01321.04 115.1187.     

Insulin sensitivity predicts glycemia after a protein load

Protein ingestion results in small but distinct changes in plasma glucose and insulin. We hypothesized that the glycemic and/or insulin response to protein might be related to the degree of insulin sensitivity. Our aim was to determine the relationships between insulin sensitivity (assessed by euglycemic-hyperinsulinemic clamp) and postprandial glucose, insulin, C-peptide, and glucagon responses to a 75-g protein meal and a 75-g glucose load. Sixteen lean healthy Caucasian subjects (mean +/- SD age, 25 +/- 6 years; body mass index [BMI], 23.1 +/- 1.7 kg/m2) participated in the study. After the protein meal, the mean plasma glucose declined gradually below fasting levels to a nadir of -0.36 +/- 0.46 mmol/L from 60 to 120 minutes, showing wide intraindividual variation. Insulin sensitivity (M value) was 1.1 to 3.9 mmol/L/m2 min in the subjects and correlated inversely with the plasma glucose response to the protein meal (r = -.58, P = .03), ie, the most insulin-sensitive subjects showed the greatest decline in plasma glucose. In contrast, there was no correlation between insulin sensitivity and the insulin or glucagon response to the protein load, or between the M value and the metabolic responses (glucose, insulin, C-peptide, and glucagon) to the glucose load. Our study suggests that the net effect of insulin and glucagon secretion on postprandial glucose levels after a protein meal might depend on the individual's degree of insulin sensitivity. Gluconeogenesis in the liver may be less susceptible to inhibition by insulin in the more highly resistant subjects, thereby counteracting a decline in plasma glucose.     

Dose-kinetics of pancreatic alpha- and beta-cell responses to a protein meal in normal subjects

A protein meal is well known to induce a prompt secretion of insulin and glucagon. However, the data regarding the dose-response relationship between the protein meal and the insulin and glucagon responses are sparse. This study assessed the effects of ingestion of protein meals of varying amounts on plasma glucose [S], insulin [I], and glucagon [G] concentrations in eight normal subjects. Protein meals were administered after an overnight fast in a randomized sequence at intervals of 10 days in four different quantities: 250 mg/kg body weight (BW) (A), 500 mg/kg BW (B), 1 g/kg BW (C), and 2 g/kg BW (D). Mean S levels were not significantly altered following A, B, or C, although significant decreases in S responses were noted after C and D as reflected by absolute changes (delta) and/or the cumulative responses (CR) and the areas under the curve (sigma). Mean I increased promptly to peak concentration by 30 minutes, although in individual subjects the peak was achieved either at 30 or 60 minutes following all protein meals. The increase was progressively greater and the return was delayed with increasing quantities resulting in progressive elevations in delta I and percent increase from basal concentration (%), as well as CRI and sigma I. G increased following all protein meals as well. The mean peak G concentrations were achieved by 90 minutes, although in individual subjects the peak G was reached at 90 or 120 minutes, a significant delay in comparison to the peak I levels. G returned to base line only following ingestion of A during the study period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Physiological concentrations of cholecystokinin stimulate amino acid-induced insulin release in humans

After a meal, hormones released from the gut potentiate insulin release. This study was undertaken to determine if physiological concentrations of plasma cholecystokinin (CCK) stimulate insulin secretion in man. Employing a specific CCK bioassay, postprandial CCK levels were determined in normal subjects. Ingestion of a mixed liquid meal stimulated an increase in circulating CCK from a mean fasting level of 0.9 +/- 0.2 (SEM) pmol/L to a mean peak level of 7.1 +/- 1.1 pmol/L within 10 min of feeding. After 30 min the mean CCK level fell to 3.5 pmol/L and remained elevated for the remainder of the 90-min experiment. Eight subjects underwent 40-min infusions of either arginine (15 g), mixed amino acids (15 g), or glucose (30 g) with or without the simultaneous infusion of CCK-8. Since CCK-8 has full biological potency, this form was chosen for infusion to reproduce total CCK bioactivity in plasma. CCK-8 was infused at rates of 12 or 24 pmol/kg X h, producing steady state plasma CCK levels of 4.5 +/- 0.7 and 8.2 +/- 1.1 pmol/L, respectively, spanning the range of normal postprandial levels. CCK alone had no effect on insulin, glucose, or glucagon levels. Administration of arginine alone stimulated insulin from a mean basal level of 12.8 +/- 1.3 microU/mL to a peak level of 41.3 +/- 5.4 microU/mL. Infusion of CCK at 12 and 24 pmol/kg X h augmented arginine-stimulated insulin levels to peaks of 62.5 +/- 13.9 and 63.0 +/- 4.0 microU/mL, respectively. Moreover, CCK nearly doubled the total amount of insulin secreted during the arginine infusion. A similar potentiation of glucagon release was found with both doses of CCK. In addition, infusion of a mixture of amino acids with and without concomitant CCK infusions revealed that CCK potentiated the insulin release induced by mixed amino acids. In contrast to the potent effect of CCK on amino acid-induced insulin release, infusions of CCK together with glucose caused no enhancement of glucose-stimulated insulin release. These results demonstrate that physiological concentrations of CCK potentiate amino acid (but not glucose)-induced insulin secretion in man. These data suggest, therefore, that CCK may have a role in man as a modulator of insulin release.