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Biomedical subjects

A H Rubenstein

Publications and source records attributed to A H Rubenstein.

At least 37 records · Page 2Linked to original sources
PubMed1990

Effect of temporal distribution of calories on diurnal patterns of glucose levels and insulin secretion in NIDDM.

The effect of different temporal patterns of calorie intake on plasma glucose, serum insulin, and insulin secretion rates was examined in six patients with moderately well controlled non-insulin-dependent diabetes mellitus (NIDDM). Patients were studied on three separate occasions over 26 h. Total calories and food composition (50% carbohydrate, 15% protein, and 35% fat) were kept constant, but the pattern of calorie intake was varied. In study A (similar meal size), calories were distributed as 30, 40, and 30% at breakfast, lunch, and dinner, respectively. In study B (3 snacks, 3 meals), each subject ate three meals of 20, 20, and 30% of calories for breakfast, lunch, and dinner, respectively, and three snacks, each comprising 10% of calories, presented 2.5 h after the meal. In study C (large dinner), 10% of calories were consumed at breakfast, 20% at lunch, and 70% at dinner. Glucose, insulin, and C-peptide concentrations were measured at 15- to 30-min intervals. Insulin secretion rates were calculated from C-peptide levels with individually derived C-peptide clearance parameters. The different eating patterns were associated with only modest differences in overall levels of glucose and insulin secretion. Daytime insulin secretion was lowest when most of the daily calorie intake occurred in the form of a large dinner. Overnight levels of glucose and insulin secretion rates did not differ for the three eating patterns, and the morning glucose levels were also unaffected by the pattern of calorie intake on the previous day. A morning rise of glucose of greater than 0.28 mM occurred consistently only when dinner was of moderate size (30% of total calories).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1989

Glyburide enhances the responsiveness of the beta-cell to glucose but does not correct the abnormal patterns of insulin secretion in noninsulin-dependent diabetes mellitus.

Eleven patients with noninsulin-dependent diabetes mellitus were studied before and after 6-10 weeks of glyburide therapy. Patients were studied during a 24-h period on a mixed diet comprising 30 Cal/kg divided into three meals. The following day a hyperglycemic clamp study was performed, with glucose levels clamped at 300 mg/dL (16.7 mmol/L) for a 3-h period. Insulin secretion rates were calculated by deconvolution of peripheral C-peptide concentrations using individual C-peptide clearance kinetics derived after bolus injection of biosynthetic human C-peptide. After 6-10 weeks on glyburide, the identical studies were repeated. In response to glyburide, the fasting plasma glucose level decreased from 12.3 +/- 1.2 to 6.8 +/- 0.9 mmol/L. Although the mean glucose over the 24 h of the meal study decreased from 12.7 +/- 1.4 to 10.8 +/- 1.2 mmol/L, postprandial hyperglycemia persisted on therapy, and after breakfast, glucose levels exceeded 10 mmol/L and did not return to fasting levels for the remainder of the day. Fasting serum insulin, plasma C-peptide, and the insulin secretion rate were not different before (152 +/- 48 pmol/L, 0.82 +/- 0.16 pmol/mL, and 196 +/- 34 pmol/min, respectively) and after (186 +/- 28 pmol/L, 0.91 +/- 0.11 pmol/mL, and 216 +/- 23 pmol/min, respectively) glyburide treatment despite lowering of the glucose level. However, average insulin and C-peptide concentrations over the 24-h period increased from 366 +/- 97 pmol/L and 1.35 +/- 0.19 pmol/mL to 434 +/- 76 pmol/L and 1.65 +/- 0.15 pmol/mL, respectively. The total amount of insulin secreted over the 24-h period rose from 447 +/- 58 nmol before therapy to 561 +/- 55 nmol while receiving glyburide. Insulin secretion was demonstrated to be pulsatile in all subjects, with periodicity ranging from 2-2.5 h. The number of insulin secretory pulses was not altered by glyburide, whereas pulse amplitude was enhanced after lunch and dinner, suggesting that the increased insulin secretion is characterized by increased amplitude of the individual pulses. In response to a hyperglycemic clamp at 300 mg/dL (16.7 mmol/L), insulin secretion rose more than 2-fold, from 47 +/- 9 nmol over the 3-h period before treatment to 103 +/- 21 nmol after glyburide therapy. We conclude that the predominant mechanism of action of glyburide in patients receiving therapy for 6-10 weeks is to increase the responsiveness of the beta-cell to glucose.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Glucose↗
PubMed1988

An islet amyloid peptide is derived from an 89-amino acid precursor by proteolytic processing.

Amyloid deposits occurring in the islets of Langerhans in patients with noninsulin-dependent diabetes mellitus and some insulinomas contain a 37-amino acid peptide that is structurally related to calcitonin gene-related peptide. We have identified three cDNA clones encoding islet amyloid polypeptide (IAPP) or diabetes-associated peptide (DAP) by oligonucleotide screening of a lambda gt10 human insulinoma cDNA library. Two of the three cDNAs contained a domain encoding IAPP/DAP but had an intron-like sequence in their 5' region. The other cDNA contained an open reading frame encoding an 89-amino acid precursor having a typical signal peptide followed by a small prohormone-like sequence containing within it the IAPP/DAP peptide bracketed at its NH2 and COOH termini by Lys-Arg and Gly-Lys-Arg, respectively. These data indicate that this amyloid peptide is generated by proteolytic processing similar to that for proinsulin and other islet prohormones and also that the peptide may be carboxyamidated. The isolation of cDNA clones having 5'-unprocessed intron-like sequences suggests that inefficient or alternative splicing of this mRNA occurred in the insulinoma.

Amino Acid Sequence↗
PubMed1988

Severe hypoglycemia attributable to surreptitious injection of insulin in a mare.

A mare with signs of hypoglycemia had high serum insulin concentrations before it was euthanatized. High pressure liquid chromatography revealed that the insulin in the mare's blood was of commercial origin. Surreptitious insulin injection has been suspected as the cause of several suspicious deaths of insured horses. The use of high-pressure liquid chromatography should help put an end to this practice.

Animals↗
PubMed1988

Hormone and metabolite plasma levels after oral glucose in bulimia and healthy controls.

Bulimia patients claim to crave sweets and since as clinical evidence suggests that the food consumed during eating binges often contains large amounts of carbohydrates, hormones involved in carbohydrate metabolism might be affected in bulimia. We therefore performed a 4-hr glucose tolerance test (GTT), using 100 g oral glucose and inquired about attitudes toward sweets. Thirteen female patients, with a mean age of 23.3 years, who had had bulimia from 3 to 7 years but whose binge-eating/vomiting behavior was largely controlled at the time of testing, were compared to 14 age-matched healthy female controls with a mean age of 24.4 years. All bulimic patients and most controls had liked sweets as children and still liked sweets. Significantly more bulimic patients than controls stated they overate on sweets and avoided sweets. Glucose utilization and the insulin, glucagon, growth hormone (GH), and pancreatic polypeptide (PP) response curves in the bulimic patients were within the normal range. Fasting plasma levels of glucose, insulin, glucagon, GH, cortisol, free fatty acids (FFA), and PP were not different from controls. There was a trend in bulimic patients to have lower plasma FFA levels and higher plasma cortisol levels during the GTT than controls. The findings suggest that, given body weight maintenance and adequate nutrition, patients with bulimia nervosa have normal glucose tolerance and normal hormonal responses following an oral glucose load.

Adult↗
PubMed1988

Eating attitudes and glucose tolerance in anorexia nervosa patients at 8-year followup compared to control subjects.

This study analyzed eating attitudes and plasma glucose, insulin, unesterified fatty acid (FFA), human growth hormone (GH), and cortisol responses to an oral (100 g) glucose load in 26 female anorexia nervosa patients at an 8-year outcome evaluation in comparison to 14 age-matched female control subjects. Recovered patients who were of normal body weight and had cyclical menstruation (n = 19) showed glucose tolerance curves and insulin, cortisol, and GH responses that were indistinguishable from those of normal subjects, although patients tended to be more diet-conscious than controls and showed elevated fasting FFA levels. Two of 19 recovered patients met criteria for impaired glucose tolerance. Nonrecovered patients (n = 7) showed abnormal eating attitudes at an average underweight of 20% with persistent amenorrhea or oligomenorrhea. They had high fasting FFA plasma levels, significantly greater than normal rises in plasma glucose, a significant delay in serum insulin secretion, higher mean glucose levels before and after controlling for amount of exercise, and paradoxical release of GH. One of seven patients met criteria for diabetes mellitus and two of seven had impaired glucose tolerance. The findings suggest that fasting plasma FFA levels may reflect patients' eating and exercise habits more accurately than their verbal or written reports.

Adult↗
PubMed1988

A mutant human proinsulin is secreted from islets of Langerhans in increased amounts via an unregulated pathway.

A coding mutation in the human insulin gene (His-B10----Asp) is associated with familial hyperproinsulinemia. To model this syndrome, we have produced transgenic mice that express high levels of the mutant prohormone in their islets of Langerhans. Strain 24-6 mice, containing about 100 copies of the mutant gene, were normoglycemic but had marked increases of serum human proinsulin immunoreactive components. Biosynthetic studies on isolated islets revealed that approximately 65% of the proinsulin synthesized in these mice was the human mutant form. Unlike the normal endogenous mouse proinsulin, which was almost exclusively handled via a regulated secretory pathway, up to 15% of the human [Asp10]proinsulin was rapidly secreted after synthesis via an unregulated or constitutive pathway, and approximately 20% was degraded within the islet cells. The secreted human [Asp10]proinsulin was not processed proteolytically. However, the processing of the normal mouse and human mutant proinsulins within the islets from transgenic mice was not significantly impaired. These findings suggest that the hyperproinsulinemia of the patients is the result of the continuous secretion of unprocessed mutant prohormone from the islets via this alternative unregulated pathway.

Animals↗
PubMed1988

Dose-dependent effects of oral and intravenous glucose on insulin secretion and clearance in normal humans.

Insulin secretion and clearance were studied in 2 groups of 7 normal subjects who each received 25, 50, and 100 g of glucose either orally or intravenously (iv) on separate occasions. Insulin secretion rates were calculated during a 1-h base line and for 5 h after glucose administration from a two-compartmental analysis of peripheral C-peptide concentrations using individual kinetic parameters derived after iv bolus injections of biosynthetic human C-peptide. Incremental glucose areas after oral or iv glucose increased as a function of the glucose dose (P = 0.0001). Incremental insulin secretion increased with increasing doses of both oral and iv glucose (P = 0.0001). The metabolic clearance rate (MCR) of endogenous insulin was calculated as the ratio of the total area under the insulin secretion rate curve and the simultaneous peripheral insulin concentration curve. The basal MCR was 1,879.5 +/- 110.5 ml/min (mean +/- SE). The poststimulatory MCR decreased with increasing doses of both oral and iv glucose concomitant with the greater insulin secretory response (P = 0.0014). This decrease in insulin clearance was not significantly different between oral and iv administration of glucose (P = 0.495). In conclusion diminished insulin clearance may be seen after marked stimulation of insulin secretion with larger doses of oral and iv glucose.

Administration, Oral↗
PubMed1988

Oscillations in insulin secretion during constant glucose infusion in normal man: relationship to changes in plasma glucose.

Peripheral plasma or serum concentrations of glucose, insulin, C-peptide, glucagon, and cortisol and insulin secretory rates (ISR) were determined at 15-min intervals in eight normal subjects during a constant iv infusion of 4.5 mg glucose/kg.min for a 24-h period. During each sampling interval, the secretory rate of insulin was calculated by deconvolution of the peripheral plasma C-peptide concentration using C-peptide kinetic parameters derived after bolus injections of C-peptide in individual subjects. Periodogram analysis of the individual glucose curves demonstrated a circadian rhythm in all subjects, with a major nocturnal acrophase occurring at an average clock time of 0228 h (range, 0045-0350 h). In five of the eight subjects, a minor acrophase occurred at an average time of 1774 h (range, 1530-2045 h). This diurnal variation in plasma glucose levels was not paralleled by a similar pattern in insulin secretion. Although glucose was infused at a constant rate, significant pulses were found in glucose, insulin, and C-peptide levels and ISR; the pulse durations of these parameters were 182 +/- 30 (+/- SE), 89 +/- 5, 100 +/- 8, and 85 +/- 5 min, respectively, and their periodicities were 208 +/- 33, 106 +/- 7, 114 +/- 10, and 106 +/- 7 min. The durations and frequencies for pulses of insulin, C-peptide, and ISR were not significantly different, whereas glucose pulses had a longer duration and were less frequent (P less than 0.05, by analysis of variance). On the average, 54 +/- 9% of the C-peptide pulses and 47 +/- 8% of the ISR pulses were concomitant with a pulse in glucose levels. Moreover, approximately half of the C-peptide and ISR pulses that were not concomitant with a glucose pulse occurred in synchrony with a shoulder on the up-stroke or down-stroke of glucose pulses. Analysis of glucagon and cortisol profiles revealed no significant associations with the insulin and glucose oscillations. In conclusion, during a constant glucose infusion in normal subjects, regular oscillations of insulin secretion occur at 80- to 120-min intervals. Their tight coupling with glucose oscillations and the lack of association with fluctuations of glucagon and cortisol suggest that these oscillations represent a dynamic property of the insulin-glucose feedback loop.

Adult↗
PubMed1988

Peripheral insulin parallels changes in insulin secretion more closely than C-peptide after bolus intravenous glucose administration.

The changes in peripheral serum insulin and plasma C-peptide levels and in the insulin secretory rate in response to iv glucose (0.5 g/kg BW) administration were studied in seven normal subjects. Insulin secretory rates were calculated according to a two-compartment model of distribution for C-peptide, using individual C-peptide kinetics calculated from iv bolus injections of biosynthetic human C-peptide. The mean plasma glucose level increased from a fasting level of 5.1 +/- 0.1 (+/- SE) to a peak of 24.0 +/- 1.0 mmol/L at 3 min and reached basal levels 101 +/- 6 min after glucose administration. The mean serum insulin value increased from 50 +/- 12 to a peak of 405 +/- 58 pmol/L at 3 min and then declined to fasting levels 139 +/- 14 min after the stimulus. In contrast, the mean plasma C-peptide level increased from 390 +/- 50 to a peak of 1460 +/- 210 pmol/L at 3 min and only began declining 45 min after glucose administration, reaching fasting levels 191 +/- 15 min after the stimulus. The mean insulin secretory rate increased from 69.8 +/- 19.9 to a peak of 1412.7 +/- 159.1 pmol/min at 3 min (15.3 +/- 2.5-fold elevation over baseline) and reached basal levels 135 +/- 12 min after the stimulus. The clearance of endogenous insulin during the basal period (2.505 +/- 0.365 L/min) and that during the 4 h after the stimulus (2.319 +/- 0.230 L/min) were similar. In conclusion, after bolus iv glucose administration: 1) the insulin secretory rate is more closely represented by changes in peripheral serum insulin than in plasma C-peptide levels; and 2) no change in endogenous insulin clearance occurs.

Adult↗
PubMed1988

Reduction of insulin clearance during hyperglycemic clamp. Dose-response study in normal humans.

Insulin secretion and clearance were studied in eight normal subjects who underwent hyperglycemic clamp studies at plasma glucose levels of 120, 225, and 300 mg/dl on three occasions. Insulin secretion rates were calculated during a 1-h baseline period and during 3 h of glucose clamping from a two-compartmental analysis of peripheral C-peptide concentrations with individual kinetic parameters derived after intravenous bolus injections of biosynthetic human C-peptide. At the 300-mg/dl clamp level, the insulin secretion rate increased to a value 9.9 +/- 0.7 times that of basal at the end of the clamp (mean +/- SE), whereas over the same period, the peripheral insulin concentrations increased to a greater extent, reaching a value 15.4 +/- 1.2 times that of basal (P = .002). This greater relative increase in the insulin concentration in comparison with the corresponding insulin secretion rate suggests a reduction in the clearance of endogenous insulin. A similar trend was seen at the 225-mg/dl clamp level, but the relative increase in the insulin concentration (9.9 +/- 1.5 times that of basal) was not significantly higher than the relative increase in the insulin secretion rate (8.1 +/- 0.5 times that of basal, P = .17). At the 120-mg/dl clamp level, the relative increases in the insulin secretion rate (2.7 +/- 0.2 times that of basal) and the insulin concentration (2.4 +/- 0.2 times that of basal) were similar (P = .26), indicating no reduction in endogenous insulin clearance during moderate stimulation of insulin secretion. In conclusion, a reduction in endogenous insulin clearance occurs during greater stimulation of insulin secretion at higher glucose-clamp levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Day-long integrated serum insulin and C-peptide profiles in patients with NIDDM. Correlation with urinary C-peptide excretion.

To determine whether non-insulin-dependent diabetes mellitus (NIDDM) is characterized by day-long hypoinsulinemia, we measured 24-h serum profiles for glucose, insulin, and C-peptide by use of a constant-rate blood-withdrawal technique in diabetic and control subjects fed isocaloric meals. When only lean subjects were considered, diabetic subjects (relative body weight 0.99 +/- 0.3) and control subjects (relative body weight 0.95 +/- 0.03) had similar 24-h integrated serum insulin concentrations (13.4 +/- 2.5 vs. 16.1 +/- 2.0 microU/ml, P NS) due to the offsetting effects of increased basal levels and decreased postprandial responses in NIDDM. In contrast, both basal and meal-stimulated insulin levels were decreased in obese NIDDM subjects (relative body weight 1.39 +/- 0.07) compared with obese control subjects (relative body weight 1.60 +/- 0.08), resulting in a 61% reduction in the 24-h integrated insulin value (18.7 +/- 1.5 vs. 48.4 +/- 13.7 microU/ml). Thus, the capacity to increase 24-h integrated serum insulin as a function of relative body weight was impaired in NIDDM subjects (r = 0.27, P NS) compared with control subjects (r = .70, P less than .01). In contrast, 24-h integrated C-peptide was decreased (P less than .01) in both lean (0.92 +/- 0.13 pM/ml) and obese (1.52 +/- 0.19 pM/ml) NIDDM patients compared with the respective control groups (1.50 +/- 0.13 and 3.03 +/- 0.44 pM/ml). The molar ratio of 24-h integrated C-peptide to insulin was diminished in lean but not obese NIDDM compared with control subjects. A 3-wk period of intensive insulin therapy led to normalization of the mean 24-h integrated insulin (but not integrated serum C-peptide) value in NIDDM compared with a control group that had an identical mean relative body weight. The 24-h urinary C-peptide measured on the same day as the serum profile was correlated (P less than .01) with both the 24-h integrated serum insulin (r = .69) and C-peptide (r = .67) concentrations in control subjects but not in NIDDM subjects (r = .20 and .04, respectively, P NS). Additionally, the urinary clearance of C-peptide was increased in NIDDM (38.1 +/- 7.8 vs. 20.4 +/- 1.7 ml/min in control subjects, P less than .05) and varied with treatment status (26.0 +/- 4.6 ml/min after insulin therapy).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1988

Reevaluation of urine C-peptide as measure of insulin secretion.

Urine C-peptide (UCP) has been proposed as a measure of insulin secretion, because insulin and C-peptide are consecreted in equimolar concentrations by the pancreatic beta-cell. The validity of this approach was tested by comparing insulin secretion rates, calculated by application of a two-compartmental analysis of peripheral C-peptide concentrations, with UCP excretion rates. Insulin secretion and UCP excretion with subjects on a mixed diet were simultaneously measured over a 24-h period in 13 patients with noninsulin-dependent diabetes mellitus and in 14 matched nondiabetic control subjects. The fraction of secreted C-peptide that was excreted in the urine (fractional C-peptide excretion) showed considerable intersubject variability in the diabetic (11.3 +/- 1.6%, range 3.9-20.8) and control (8.0 +/- 1.7%, range 1.1-27.9, P = .07) subjects (means +/- SE). UCP clearance demonstrated a similar degree of variability and was not significantly different (P = .07) between diabetic (23.8 +/- 3.0 ml/min) and control (16.5 +/- 2.7 ml/min) subjects. In control subjects, the 24-h insulin secretion rate correlated more closely with the fasting insulin secretion rate (r = .97, P = .0001), fasting C-peptide (r = .81, P = .0005), and fasting insulin (r = .80, P = .0005) concentrations than with the 24-h UCP excretion rate (r = .62, P = .02). Similar results were obtained in the diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

C-Peptide↗
PubMed1987

Selective suppression of hepatic glucose output by human proinsulin in the dog.

By using the euglycemic glucose-clamp technique we have observed the effects of comparable low dose proinsulin and insulin infusions on isotopically determined glucose turnover in 20 anesthetized dogs. In each animal somatostatin (SRIF) infusion was used to suppress endogenous pancreatic hormone secretion and basal glucagon was replaced. Peripheral proinsulin (0.083 micrograms X kg-1 X min-1) and insulin (350 microU X kg-1 X min-1) levels 15- to 20-fold higher than insulin on a molar basis, based on previous observations that proinsulin has only 5-10% the biologic potency of insulin. Three groups of infusion studies were performed: SRIF and glucagon (n = 5); SRIF, glucagon, and proinsulin (n = 10); and SRIF, glucagon, and insulin (n = 5). The mean serum proinsulin level of 2.43 +/- 0.36 pmol/ml achieved represented a 17-fold excess compared with the mean serum insulin level of 0.14 +/- 0.03 pmol (20 +/- 4 microU/ml). At these concentrations, both hormones reduced hepatic glucose production rates by approximately 50% to 2.0 +/- 0.2 mg X kg-1 X min-1 and 1.8 +/- 0.5 mg X kg-1 X min-1, respectively. In contrast, proinsulin failed to stimulate peripheral glucose utilization, whereas insulin led to a 2.0 +/- 0.3 mg X kg-1 X min-1 increment (approximately 50% increase) in glucose uptake (P less than 0.05). Thus at low infusion rates proinsulin exerts its effect predominantly by suppressing hepatic glucose production without measurable stimulation of peripheral glucose disposal. In contrast, for a comparable degree of hepatic glucose output suppression, insulin also significantly stimulates glucose disposal.

Animals↗
PubMed1987

The effect of biosynthetic human proinsulin on the hepatic response to glucagon in insulin-deficient diabetes.

The relative tissue specificities of biosynthetic human proinsulin and porcine insulin were compared in eight insulin-deficient diabetic patients. Variable proinsulin and insulin infusions were administered iv for at least 18 h on separate occasions to achieve euglycemia. Once equivalence with respect to this end point was established, the paired infusions were made constant and compared with respect to their effect on plasma glucose, hepatic glucose output (Ra), glucose utilization, glucose clearance, and blood beta-hydroxybutyrate, alanine, and glycerol in response to a glucagon infusion (3 ng/kg X min). Basal Ra did not differ between euglycemia established using proinsulin vs. insulin [1.92 +/- 0.12 vs. 1.65 +/- 0.07 mg/kg X min] when data were analyzed by multivariate analysis of variance; likewise, the increment in Ra in response to glucagon infusion did not differ between the two treatments (1.26 +/- 0.22 vs. 1.17 +/- 0.24 mg/kg X min). Blood beta OHB, alanine, and glycerol also did not differ between the insulin and proinsulin treatments. Under these conditions of prolonged infusion in which the differences in clearance properties between proinsulin and insulin do not play a role and which maintain basal euglycemia, the two compounds equally limit the response to a stimulus to hepatic glucose production. Under nonsteady state conditions, when the differences in clearance rates are operative, proinsulin may have relatively greater effects on Ra than do doses of insulin that are biologically equivalent after prolonged infusions.

Adult↗
PubMed1987

Insulin secretion and clearance. Comparison after oral and intravenous glucose.

Insulin secretion and clearance in response to the administration of oral and intravenous glucose was investigated in nine normal men. C-peptide metabolic kinetics were calculated by analysis of individual C-peptide decay curves after the bolus injection of biosynthetic human C-peptide. Glucose was administered to the subjects on three occasions: as a 75-g oral dose, a 75-g i.v. infusion, and an intravenous glucose infusion at a variable rate adjusted to mimic the peripheral glucose levels obtained after the oral glucose load (matching experiment). Glucose, insulin, and C-peptide concentrations were measured for the subsequent 5 h. The glucose level after the oral glucose load (115.9 +/- 2.6 mg/dl, mean +/- SE) closely approximated that after the matching experiment (120.5 +/- 2.5 mg/dl) but was significantly lower than after 75 g i.v. glucose (127.7 +/- 3.4 mg/dl, P less than .05). Analysis of the areas under the peripheral concentration curves (60-360 min) showed that the responses of both insulin (52.7 +/- 5.6 and 46.5 +/- 4.5 pmol.ml-1.300 min-1) and C-peptide (252.7 +/- 27.5 and 267.0 +/- 21.6 pmol.ml-1.300 min-1) were not significantly different after the oral and 75-g i.v. glucose studies, respectively, whereas in the matching experiment, both the insulin (26.1 +/- 3.9 pmol.ml-1.300 min-1) and C-peptide (178.0 +/- 18.9 pmol.ml-1.300 min-1) responses were lower (P less than .05) than in the other two studies. Insulin secretory rates were derived from peripheral C-peptide concentrations with an open two-compartment model and individually derived model parameters. (ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗