Insulin In Normal Subjects Research Articles

Source and Amount of Carbohydrate Affect Postprandial Glucose and Insulin in Normal Subjects

To determine if source and amount of carbohydrate affected postprandial glucose and insulin responses, seven nondiabetic subjects consumed 0, 25, 50, 75 or 100 g carbohydrate (total carbohydrate minus total dietary fiber) portions of barley, spaghetti, bread or potato. By ANOVA, both source and amount of carbohydrate had significant effects on incremental response areas for capillary glucose (P = 0.001), plasma glucose (P = 0.01) and plasma insulin (P = 0.03), but there was no source × amount interaction. By regression analysis, source of carbohydrate explained a similar amount of the variability of glucose and insulin responses, 46–64%, as the amount of carbohydrate, 47–57%. Together, carbohydrate source and amount accounted for 85–94% of the variability of mean glucose and insulin responses. We conclude that, for individual foods with different glycemic indices, both source and amount of carbohydrate influence the postprandial glucose and insulin responses of nondiabetic subjects.

Skin vasoreactivity to insulin iontophoresis is reduced in elderly subjects and is absent in treated non-insulin-dependent diabetes patients

We investigated the skin vasoreactivity to insulin in normal subjects and in treated non-insulin-dependent diabetes mellitus (NIDDM) patients. We measured cutaneous perfusion by laser-Doppler flowmetry (LDF) at rest and during skin cathodal iontophoresis (six pulses of 0.1 mA each for 20 s, with 40 s interval between stimulations) of insulin (0.1 ml Humulin R 100 IU/ml diluted 1/10 with of 0.9% saline solution) in 45 healthy subjects (HS), (25 males, 20 females, aged 45 ± 18 years), and in 15 treated NIDDM patients (13 males), aged 66 ± 8 years. Fifteen of the HS were used as controls. In these 15 sex- and age-matched HS and in the patients, we assessed also the skin postischemic hyperemia by LDF. In HS cutaneous blood flux response (CBF) to iontophoresis of insulin in saline (expressed as percent changes from baseline) was significantly higher than CBF response to iontophoresis of pure saline (maximum response: 360 ± 51% versus 172 ± 42%, respectively; P < 0.001, ANOVA for repeated measures). The maximum “net” CBF response to insulin (response to insulin minus response to saline) showed a negative correlation ( r = –0.361; P < 0.01) with age in HS, and resulted significantly lower in the oldest than in the youngest HS (105 ± 40% versus 307 ± 45%, respectively; P < 0.01). No significant correlation was observed between the maximum CBF response to saline and the age of subjects. In NIDDM patients the “net” CBF response to insulin iontophoresis resulted significantly lower than in 15 sex- and age-matched control subjects (maximum response: –50 ± 89% versus 201 ± 81%, respectively; P < 0.001, ANOVA for repeated measures). No significant difference was observed between diabetics and controls, nor in basal perfusion (6.5 ± 1.3 IU versus 6.8 ± 1.7 IU, respectively) neither in the skin postischemic hyperemia (250 ±14% versus 258 ± 27%, respectively). These results confirm that insulin iontophoresis induces a skin vasodilatatory effect in normal subjects and show that this effect is reduced by aging and is absent in treated NIDDM patients. The local skin vasodilatatory effect induced by insulin seems to involve mechanisms different from those underlying the skin postischemic hyperemia.

Proinsulin, C-peptide, and insulin in normal subjects during an 8-h hyperglycemic clamp

Increased concentrations of proinsulin immunoreactive material (PIM) absolutely or relative to insulin is a characteristic finding in patients with non-insulin-dependent diabetes mellitus (NIDDM). The aim of this study was to test if 8 h or mild hyperglycemia (7-9 mmol/l) in healthy subjects could induce a preferential secretion of PIM from B cells. Serum concentrations of insulin, C-peptide and PIM were measured every 10 min during the 8 h of continuous glucose infusion in nine normal-weight healthy subjects without diabetes among their first-degree relatives. After a gradual rise in B-cell peptides, a steady state was reached. From 4 to 8 h no further difference in insulin, C-peptide or PIM concentration was found. Fasting PIM/C-peptide and PIM/insulin ratios of 0.5% and 2.3% increased during the glucose clamp to levels of 1.4% and 7.6%, respectively. Neither testing the regression slope nor comparing individual time points showed any significant difference for the PIM/C-peptide ratio from 2 to 8 h and for the PIM/insulin ratio from 3 to 8 h. These results do not support the hypothesis that an increased glucose drive per se results in an altered B-cell function with increasing PIM/C-peptide ratio. At least 8 h of mild hyperglycemia in healthy subjects does not progressively alter B-cell function.

Respective role of plasma nonesterified fatty acid oxidation and total lipid oxidation in lipid-induced insulin resistance

To investigate the respective role of nonesterified fatty acids (NEFA) oxidation and total lipid oxidation in lipid-induced insulin resistance, we measured the response of glucose metabolism to insulin in normal subjects without (control study) or with either heparin (heparin study) or triglycerides (TG) emulsion (Ivelip study) infusion. Three-step euglycemic—mild-hyperinsulinemic clamp studies were performed. Lipid and glucose metabolism were studied using indirect calorimetry and [6,6- 2H 2]glucose and [1- 13C]palmitate infusions. NEFA concentration and turnover and oxidation rates were decreased by insulin in the control study, but were maintained during the heparin and Ivelip infusion studies. Total lipid oxidation was decreased similarly in the control and heparin studies, but was increased during the Ivelip infusion. Stimulation of glucose oxidation and utilization by insulin was reduced in the Ivelip study, but not in the heparin study. Thus, peripheral insulin resistance was observed in the presence of a combined increase in total lipid and NEFA oxidation, but not during an isolated increase in NEFA oxidation. On the other hand, insulin-induced inhibition of glucose production was impaired in both the heparin and Ivelip studies. We conclude that total lipid oxidation is a major determinant of peripheral insulin resistance, whereas hepatic insulin resistance could be induced even by a moderate increase in NEFA availability.

The effects of estrogen priming and puberty on the growth hormone response to standardized treadmill exercise and arginine-insulin in normal girls and boys.

To determine the effects of puberty and estrogen priming on the GH response to standardized treadmill exercise and arginine-insulin in normal boys and girls, we performed tests in 84 normal children (41 girls and 43 boys) representing all stages of puberty. A subset of the prepubertal children received the tests twice, with or without the administration of ethinyl estradiol (40 micrograms/m2 daily) for 2 days before the tests. The peak GH response to the three tests increased significantly with pubertal stage (r = 0.57; P < 0.0001), but did not differ between boys and girls at the same stage. With advancing puberty, the percentage of normal children who failed to attain a GH level greater than 7 micrograms/L during any of the three tests declined from 61% at pubertal stage 1 to 44% at stage 2, 11% at stage 3, and 0% at stages 4 and 5. Administration of estrogen to the prepubertal subjects raised the normal range for the peak GH response to the three tests from 1.9-20.3 to 7.2-40.5 micrograms/L. We conclude that both puberty and estrogen administration significantly increase the peak GH response to exercise, arginine, or insulin in normal subjects. Moreover, the conventional criterion that the peak GH response to three stimulation tests should exceed 7 micrograms/L was applicable in our study only to subjects who had attained pubertal stage 4 or 5 or who had received estrogen administration.

Biological Activity of Nasally Administered Insulin in Normal Subjects

Nasally administered (IN) insulin has been advocated as a potentially useful alternative to subcutaneously administered regular insulin because of its more rapid onset and time to peak action and its shorter duration of action. This study further defines the pharmacodynamics of IN insulin by using a euglycemic clamp technique to determine the bioavailability of IN insulin as compared with intravenous (IV) insulin, and to ascertain whether multiple sequentially administered doses of IN insulin alter pharmacodynamics. Eight normal volunteers received 2 control doses of IV insulin (0.05 U/kg), and 3 high doses (0.7 U/kg) and 3 low doses (0.35 U/kg) of IN insulin with an absorption enhancer (tauro-24,25 dihydrofusidate) given sequentially over a 2 day period. A euglycemic clamp was performed with a Biostator (Ames) that infused dextrose to keep the subject's blood glucose at his fasting level. Analysis of dextrose infusion curves for the low and high doses of IN insulin revealed an onset of action of 9.4 +/- 0.4 and 10.5 +/- 0.3 minutes, time to peak action of 20.6 +/- 5.6 and 23.7 +/- 4.4 minutes and duration of action of 82.1 +/- 5.2 and 95 +/- 5.7 minutes respectively. Both the onset of action and time to peak action were slightly longer (P less than .05) for the high as compared with the low dose IN insulin, although this should not represent a clinically significant difference. The total dextrose requirement was 21.9 +/- 2.3 g for the low dose IN insulin and 34.1 +/- 3.3 g for the high dose IN insulin, the latter value being significantly greater (P less than .01) than the former.(ABSTRACT TRUNCATED AT 250 WORDS)

Islet Hormonal Regulation of Glucose Turnover during Exercise in Type 1 Diabetes*

A decline in plasma insulin and an increase in glucagon are known to occur during intense and/or prolonged exercise. However, it is not established whether changes in insulin and glucagon secretion are involved in the precise matching of hepatic glucose production to the enhanced glucose uptake by muscle during brief, low intensity exercise. We studied the effects of 30-min cycle exercise at 40% of maximal aerobic capacity in healthy subjects and C-peptide-deficient subjects with type 1 diabetes (IDDM) using [3-3H]glucose to estimate glucose turnover. Diabetic subjects were studied during continuous iv insulin infusion, which normalized glucose kinetics before experimental perturbations. In control (saline-infused) experiments, endogenous glucose appearance (Ra) increased by 80-90% above baseline to match the increase in glucose disappearance in both normal and IDDM subjects, even though the latter exercised at fixed levels of plasma free insulin, averaging 203 +/- 19 pmol/L. In other experiments, somatostatin was infused, and glucagon (1.0 ng/kg.min) and insulin (at two different rates) were maintained at constant levels. Infusion of insulin in normal subjects at doses sufficient to maintain constant peripheral plasma insulin was associated with no apparent effect on glucose turnover (plasma insulin, 80 +/- 21 pmol/L, compared to 52 +/- 5 pmol/L during saline; P = NS). However, insulin infusion at doses that normalized the portal insulin concentration (approximately 208 pmol/L) together with glucagon replacement inhibited the rise in glucose production in both normal and IDDM subjects. There were similar 45-55% reductions (P less than 0.03) of the increase in Ra seen with exercise in control experiments. When peripheral plasma free insulin (and presumably portal levels as well) were increased by about 20% in this experimental setting in IDDM (278 +/- 43 pmol/L), the suppression of Ra was even more profound, and Ra failed to increase at all with exercise. We conclude that the hormonal regulation of Ra in brief duration exercise in man does not necessitate the decrements in portal venous insulin observed under more intense exercise conditions as long as an exercise-induced glucagon secretory response can occur. Glucagon secretion alone cannot prevent hypoglycemia when portal venous insulin concentrations are increased by minimal amounts, such as in insulin-treated diabetics.

Kinetic models for plasma disappearance of insulin in normal subjects.

Three theoretical kinetic models for plasma disappearance of insulin were examined in six normal men. The models allowed for the existence of non-saturable and/or saturable mechanisms. Constant infusion of porcine insulin at different rates was used to achieve different levels of steady state plasma insulin concentrations, while normoglycaemia was secured by a glucose clamp technique. Appropriate validation procedures demonstrated that one of the three models was superior to the others in describing the relationship between the exogenous insulin infusion rate Iex and the steady state plasma insulin concentration C: Iex = -Iend + k2 X C/(k3 + C), where Iend is the endogenous post-hepatic insulin delivery rate. Thus, only saturable mechanism(s) could be demonstrated. The median value of k2 (the maximal insulin disappearance rate) and k3 (the plasma insulin concentration at which the insulin disappearance rate is half maximal) were 7.31 nmol X min.-1 and 3.89 nmol X 1-1. The median value of k2/k3 (the clearance rate of insulin for infinitesimal plasma insulin concentrations) was 25.0 ml X kg-1 X min.-1. Thus, at physiological levels of plasma insulin concentrations the metabolic clearance rate of insulin is higher than insulin clearance estimates previously reported in studies based on the assumption of first order kinetics.

How insulin resistant are patients with noninsulin-dependent diabetes mellitus?

The study was carried out to quantify the ability of physiological increases in the plasma insulin concentration to stimulate glucose disposal above basal levels in 25 normal subjects and 25 patients with noninsulin-dependent diabetes mellitus (NIDDM). Patients were sex, age, and weight matched, and glucose disposal was determined under basal conditions (plasma insulin, approximately 10 microU/ml) and after plasma insulin levels had been increased to approximately 90 microU/ml. The mean (+/- SEM) glucose disposal rate was significantly greater (P less than 0.001) under basal conditions in patients with NIDDM (110 +/- 5 mg/m2 X min) than in individuals with normal glucose tolerance (77 +/- 4 mg/m2 X min). Glucose disposal rates increased in both normal subjects and NIDDM patients when plasma insulin concentrations were increased to about 90 microU/ml; however, the increment was much greater in normal subjects. Thus, glucose disposal only rose to a mean (+/- SEM) value of 145 +/- 7 mg/m2 X min in patients with NIDDM, representing an approximate 30% increase due to insulin. In contrast, a similar elevation of plasma insulin in normal subjects resulted in an increase in glucose disposal of approximately 300%, reaching a mean (+/- SEM) value of 310 +/- 24 mg/m2 X min. These results indicate that the defect in insulin-stimulated glucose uptake is significantly greater in patients with NIDDM than has previously been found.

The relationship between plasma concentration and plasma disappearance rate of immunoreactive insulin in normal subjects.

To investigate the mechanism of insulin degradation in normal subjects, a kinetic model of insulin disappearance was constructed: insulin was assumed to be extracted from plasma by two independent processes, one saturable and one non-saturable. On the basis of these assumptions, a linear (non-proportional) relationship between steady-state plasma insulin concentration and steady-state plasma disappearance rate was predicted over the concentration range studied. Constant infusion experiments were performed on eight healthy normal subjects, normoglycaemia and fasting plasma C-peptide concentrations being maintained during the experiments. Agreement was found between the predictions of the model and the experimental results, and it is concluded that insulin degradation in normal subjects may be described in terms of two processes: one that is saturated at physiological plasma insulin concentrations and one that is apparently non-saturable over a wide concentration range.

Calcium antagonists and hormone release. I. Effects of verapamil on insulin release in normal subjects and patients with islet-cell tumor

Intravenous infusion of verapamil, an organic antagonist of calcium transport into cells, produced a marked and significant inhibition of glucose-, glucagon- and sulfonylurea-induced increases in serum insulin in normal subjects. Also, blood glucose concentrations remained significantly higher after the secretagogue plus verapamil than after the secretagogue alone. Blood glucose concentrations increased regularly after verapamil + glucagon administration indicating that verapamil is not capable of inhibiting the hepatic glycogenolysis induced by glucagon. Two patients with islet-cell tumor, treated with verapamil for 5 days, experienced a decrease in the severity and frequency of hypoglycemic attacks while “autonomous” insulin release was inhibited. The present results clearly show that calcium antagonists are capable of inhibiting insulin response to appropriate stimuli in normal subjects. Therapeutic association of calcium antagonists and sulfonylureas should be used with caution in the light of the present findings. Calcium antagonists can be useful drugs in the treatment of hypoglycemia caused by islet-cell tumor.

The effect of aprotinin on the absorption of subcutaneously injected regular insulin in normal subjects

The effect of aprotinin on the absorption of subcutaneously injected regular insulin in normal subjects

The effect of aprotinin on the absorption of subcutaneously injected regular insulin in normal subjects.

The effect of aprotinin on the absorption of regular insulin was assessed in normal man. Ten units of Actrapid insulin were subcutaneously injected together with 1.4 mg aprotinin (i.e., 0.5 ml of Trasylol) or an equivalent volume of physiologic saline (controls) into the thighs of overnight-fasted normal subjects. Aprotinin caused an increase in the rate of insulin entry into the circulation; the absolute amount of insulin that was detected in the circulation during the course of the experiment was also higher. In addition, the onset of the hypoglycemic action of exogenous insulin was significantly accelerated when insulin was administered together with aprotinin. These data suggest that aprotinin increases the absorption rate of subcutaneously injected insulin from its depot into the circulation, possibly by an inhibition of the local degradation of exogenous insulin at the injection site.

The effect of unabsorbable carbohydrate on gut hormones

Five healthy volunteers and 6 diabetics were given a mixed test meal on two occasions--once with and once without 10 g guar flour. Addition of guar caused a 47% decrease in maximum post-prandial GIP levels, a 48% decrease in blood glucose and a 48% decrease in plasma insulin in normal subjects. In diabetics, addition of guar caused a 30% reduction in maximum post-prandial GIP and 58% decrease in blood glucose. Four normal and 6 diabetic subjects were given a predominantly carbohydrate meal, again with and without 10 g guar. Addition of guar caused a 78% decrease in blood glucose and a 59% decrease in plasma insulin in normal subjects. In diabetics addition of guar caused a 71% decrease in maximum post-prandial plasma GIP and a 68% decrease in blood glucose. Lowering of post-prandial blood glucose, plasma insulin and GIP levels by guar was statistically significant in every case. Addition of guar to the predominantly carbohydrate meal caused a decrease in total plasma GLI in both normal and diabetic subjects but reached statistical significance only in the normal subjects. There was a highly significant correlation (r = 0.83; p less than 0.0005) between peak post-prandial insulin levels in normal subjects and the corresponding plasma GIP concentration. The reduction of GIP or GLI secretion may, therefore, be partly responsible for the smaller rise in plasma insulin observed in normal volunteers when guar is added to meals.

Effect of Intermittent Endogenous Hyperglucagonemia on Glucose Homeostasis in Normal and Diabetic Man

Infusion of glucagon causes only a transient increase in glucose production in normal and diabetic man. To assess the effect of intermittent endogenous hyperglucagonemia that might more closely reflect physiologic conditions, arginine (10 g over 30 min) was infused four times to 8 normal subjects and 13 insulin-dependent diabetic subjects (4 of whom were infused concomitantly with somatostatin to examine effects of arginine during prevention of hyperglucagonemia). Each arginine infusion was separated by 60 min. Diabetic subjects were infused throughout the experiments with insulin at rates (0.07-0.48 mU/kg per min) that had normalized base-line plasma glucose and rates of glucose appearance (Ra) and disappearance (Rd). Basal plasma glucagon and arginine-induced hyperglucagonemia were similar in both groups; basal serum insulin in the diabetics (16+/-1 muU/ml, P < 0.05) exceeded those of the normal subjects (10+/-1 muU/ml, P < 0.05) but did not increase with arginine. Serum insulin in normal subjects increased 15-20 muU/ml with each arginine infusion. In both groups each arginine infusion increased plasma glucose and Ra. Increments of Ra in the diabetics exceeded those of normal subjects, (P < 0.02); Rd was similar in both groups. In normal subjects, plasma glucose returned to basal levels after each arginine infusion, whereas in the diabetics hyperglycemia persisted reaching 151+/-15 mg/dl after the last arginine infusion. When glucagon responses were prevented by somatostatin, arginine infusions did not alter plasma glucose or Ra. Infusion of arginine acutely increases plasma glucose and glucose production in man solely by stimulating glucagon secretion; physiologic increments in plasma glucagon (100-150 pg/ml) can result in sustained hyperglycemia when pancreatic beta cell function is limited.

Glucose and insulin responses to diet. Effect of variations in source and amount of carbohydrate.

The influence of variations in amount of carbohydrate in the diet (45 per cent or 65 per cent of total calories) and source (sucrose or corn syrup) on plasma insulin and glucose concentrations was evaluated in eight normal men. Four diets, which were alternated in a Latin square design, were consumed for 10 days. Plasma glucose and insulin concentrations were measured during an oral glucose tolerance test and over a 24-hour period while the test diets were consumed. The 24-hour study was completed with a portable, constant withdrawal pump, which allowed samples to be collected as a series of 48 consecutive, integrated, 30-minute samples. Thus, the 24-hour mean, or integrated, concentration as well as fluctuations during the day could be determined. The 24-hour integrated concentration of glucose did not vary significantly with the dietary changes tested. In contrast, two of the three methods used, to evaluate the glucose tolerance test results indicated that high carbohydrate diets improve glucose tolerance. Glucose fluctuations were significantly greater during ingestion of diets containing corn syrup than during those containing sucrose. The percentage of dietary energy supplied as carbohydrate did not influence glucose fluctuations significantly. Diets containing corn syrup were associated with significantly higher integrated concentrations of insulin than the sucrose diets. Insulin-integrated concentrations did not vary significantly with changes in the percentage of dietary carbohydrate. The insulin response to the glucose tolerance test did not vary with the source of carbohydrate and did not accurately reflect the 24-hour mean insulin concentrations. We concluded that (1) a change in the percentage of energy supplied as carbohydrate does not significantly influence the concentration of either glucose or insulin in normal subjects; (2) concentrations of glucose throughout the day are more stable when the dietary carbohydrate is sucrose than when it is corn syrup; (3) sucrose-containing diets require significantly lower insulin concentrations to maintain euglycemia than do corn syrup–containing diets; (4) glucose and insulin responses to an oral glucose tolerance test do not accurately reflect the 24-hour glucose and insulin concentrations obtained during ingestion of the test diets.

STIMULATION OF INSULIN SECRETION BY GLUCAGON AND SECRETIN

ABSTRACT Intravenous injection of 1.0 mg glucagon brings about a marked increase in the serum concentration of insulin in normal subjects. This increase sets in before the increase in blood sugar and reaches a peak 2–8 minutes after the injection. Intravenous injection of 75 units secretin also results in a rapid increase in the serum concentration of insulin in normal subjects. This increase is less marked than that following glucagon and reaches its peak 3–4 minutes after the injection. It must be assumed that glucagon as well as secretin contribute to the pronounced increase in insulin concentration during oral administration of glucose.

Urine insulin in normal subjects

Immunochemical insulin is measurable in urine by the double-antibody assay procedure. Its excretion per hour correlates with the mean serum level and its “clearance” does not vary with changes in serum insulin concentrations. In 28 normal subjects the “insulin clearance”, measured during an oral GTT, was low (mean 0.42 ml./min.; range 0.23–0.87 ml./min.) and varied with the “creatinine clearance” and less with urinary albumin. This low “clearance” suggests that either serum insulin is bound to a larger protein or polymerized, or that it is avidly reabsorbed by the renal tubules after glomerular filtration. The log-mean basal (overnight) urine insulin level in 28 normal subjects was 215 μU/hr. (range 89–499). During the 2 hr. following 50 Gm. oral dextrose the level rose to a log-mean of 834 μU/hr. (range 330–2370).

Effects of insulin on triglyceride and free fatty acid metabolism in man

The response of triglyceride and freefatty acid (FFA) concentrations were compared after acute or prolonged mild hypoglycemia was induced by insulin in normal subjects. Intravenously administered glucagon-free insulin (0.12 units/Kg.) caused acute falls in the levels of plasma glucose and FFA, with secondary rises in each moiety. Concomitantly, no consistent alteration was noted in plasma triglycerides during the induction of hypoglycemia, during the rebound phase, or 24 hours after the acute induction of hypoglycemia. During constant infusions of 0.01–0.02 units of insulin/Kg./hour for periods of 5–8 hours, plasma glucose remained suppressed. After initial decreases rebounds in FFA levels were observed during the infusions, but especially after discontinuing the infusions. Plasma triglycerides declined in 3 of 7 patients during the infusions, and triglyceride levels of all subjects were depressed to 55–84 per cent of control values on the morning after the infusions. During a constant infusion of palmitic acid-1-C14, acute and sustained insulin administration uniformly suppressed the rate of appearance of C14 label in plasma triglycerides. The mechanisms of insulin action in diminishing triglyceride levels have not been defined. The striking rebound in FFA levels following the cessation of the insulin infusions is presented as possible evidence in vivo of the inhibition, by insulin, of hormonally mediated lipolysis The response of triglyceride and freefatty acid (FFA) concentrations were compared after acute or prolonged mild hypoglycemia was induced by insulin in normal subjects. Intravenously administered glucagon-free insulin (0.12 units/Kg.) caused acute falls in the levels of plasma glucose and FFA, with secondary rises in each moiety. Concomitantly, no consistent alteration was noted in plasma triglycerides during the induction of hypoglycemia, during the rebound phase, or 24 hours after the acute induction of hypoglycemia. During constant infusions of 0.01–0.02 units of insulin/Kg./hour for periods of 5–8 hours, plasma glucose remained suppressed. After initial decreases rebounds in FFA levels were observed during the infusions, but especially after discontinuing the infusions. Plasma triglycerides declined in 3 of 7 patients during the infusions, and triglyceride levels of all subjects were depressed to 55–84 per cent of control values on the morning after the infusions. During a constant infusion of palmitic acid-1-C14, acute and sustained insulin administration uniformly suppressed the rate of appearance of C14 label in plasma triglycerides. The mechanisms of insulin action in diminishing triglyceride levels have not been defined. The striking rebound in FFA levels following the cessation of the insulin infusions is presented as possible evidence in vivo of the inhibition, by insulin, of hormonally mediated lipolysis

INSULIN I-131 BINDING IN SERUM FROM NORMAL AND DIABETIC SUBJECTS BY ULTRACENTRIFUGATION AND GEL FILTRATION.

Ultracentrifugation and gel filtration were used to test for specific insulin-I-131 binding protein in the serum of normal subjects and in patients with overt or potential diabetes. Such technics permit study of sera at physiologic pH, with physiologic concentrations of exogenous insulin added. They also eliminate the interference of electrical fields and, in ultracentrifugation, the need for artificial supporting media. Whereas a specific binding protein was readily demonstrable in the serum of insulin-treated patients with high antibody titers, there was no evidence of a protein capable of binding exogenous labeled insulin in normal subjects nor in the serum of subjects with various types of diabetes and potential diabetes. Serum from subjects who have a hyper-response of insulin to glucose loads, possibly caused by peripheral antagonism to insulin action, did not bind significant amounts of insulin-I-131.