Elevation Of Plasma Insulin Concentration Research Articles

Attenuated inhibition of L-type calcium currents by troglitazone in fructose-fed rat cardiac ventricular myocytes.

We recently reported that troglitazone, an insulin-sensitizing agent, inhibited l-type Ca current (ICa,L) more effectively in streptozotocin (STZ)-induced diabetic ventricular myocytes than in age-matched control myocytes. However, whether this agent would effectively inhibit ICa,L in an animal model of hyperinsulinemia is unknown. Using whole-cell voltage-clamp techniques, ICa,L was measured in ventricular myocytes isolated from 12 to 16 weeks on fructose-enriched feeding and age-matched control rats. Under control conditions, fructose-fed myocytes did not differ from control myocytes in membrane capacitance, current density, or voltage-dependent properties of ICa,L. Troglitazone inhibited ICa,L in both control and fructose-fed myocytes in a concentration-dependent manner. However, this inhibition was less in fructose-fed than in control myocytes; the half-maximum inhibitory concentrations of troglitazone measured at a holding potential of -50 mV were 16.9 and 9.8 micromol/L, respectively. Contrary to the STZ-induced diabetic rat, the suppressive effect of troglitazone on cardiac ventricular ICa,L was attenuated in fructose-fed rats. Persistent elevation of plasma insulin concentration may play a role in these processes.

Adding Carbohydrate to a Fat Meal Alters Post-Prandial Lipemia Without Changing Plasma Triglyceride Concentration

1492 The insulin response to a meal containing both carbohydrate and fat can alter the lipemic response to the ingested fat through changes in muscle and adipose tissue lipoprotein lipase activity. PURPOSE: Determine the effect of adding carbohydrate to a fat meal on post-prandial triglyceride and fatty acid concentrations in the blood. METHODS: 5 healthy males ingested a lipid load (0.7g fat/kg body weight) on two separate occasions: 1) fat meal alone (F), and 2) fat meal co-ingested with glucose (GF; 1 g glucose/kg body weight). Blood samples were collected hourly for 8 h and were analyzed for concentrations of plasma insulin, fatty acid, glycerol, total plasma triglycerides (TG) and TG concentrations in the chylomicron and very-low density lipoprotein fractions (separated by density gradient centrifugation). Fat oxidation was measured using indirect calorimetry before the meal and 1.5, 3.5, 5.5, and 7.5 h after the meal. RESULTS: Despite a modest elevation in plasma insulin concentration in GF vs. F (insulin AUC: 74.9 ± 17.6 and 16.4 ± 4.3 μU/ml*min; P<0.05), plasma glycerol and total TG concentration, as well as the TG concentration in the chylomicron and VLDL fractions were not different between GF and F. In contrast, the elevation in plasma insulin concentration during GF was associated with a greater plasma fatty acid concentration (0.44 ± 0.02 and 0.26 ± .01 mM; P<0.05, average values during the 6–8 h period after the meal) and a lower rate of fat oxidation (73.6 ± 4.9 and 83.0 ± 2.8 μmol/min; P<0.05) during the 8 h period after the meal. CONCLUSION: The addition of carbohydrate to a fat meal and the resultant increase in plasma insulin concentration did not alter the net hydrolysis of the ingested lipids. However, the differential effects of insulin on lipoprotein lipase activity in adipose tissue and skeletal muscle may have reduced the uptake and oxidation of fatty acids derived from exogenous lipids.

Adding Carbohydrate to a Fat Meal Alters Post-Prandial Lipemia Without Changing Plasma Triglyceride Concentration

1492 The insulin response to a meal containing both carbohydrate and fat can alter the lipemic response to the ingested fat through changes in muscle and adipose tissue lipoprotein lipase activity. PURPOSE: Determine the effect of adding carbohydrate to a fat meal on post-prandial triglyceride and fatty acid concentrations in the blood. METHODS: 5 healthy males ingested a lipid load (0.7g fat/kg body weight) on two separate occasions: 1) fat meal alone (F), and 2) fat meal co-ingested with glucose (GF; 1 g glucose/kg body weight). Blood samples were collected hourly for 8 h and were analyzed for concentrations of plasma insulin, fatty acid, glycerol, total plasma triglycerides (TG) and TG concentrations in the chylomicron and very-low density lipoprotein fractions (separated by density gradient centrifugation). Fat oxidation was measured using indirect calorimetry before the meal and 1.5, 3.5, 5.5, and 7.5 h after the meal. RESULTS: Despite a modest elevation in plasma insulin concentration in GF vs. F (insulin AUC: 74.9 ± 17.6 and 16.4 ± 4.3 μU/ml*min; P<0.05), plasma glycerol and total TG concentration, as well as the TG concentration in the chylomicron and VLDL fractions were not different between GF and F. In contrast, the elevation in plasma insulin concentration during GF was associated with a greater plasma fatty acid concentration (0.44 ± 0.02 and 0.26 ± .01 mM; P<0.05, average values during the 6–8 h period after the meal) and a lower rate of fat oxidation (73.6 ± 4.9 and 83.0 ± 2.8 μmol/min; P<0.05) during the 8 h period after the meal. CONCLUSION: The addition of carbohydrate to a fat meal and the resultant increase in plasma insulin concentration did not alter the net hydrolysis of the ingested lipids. However, the differential effects of insulin on lipoprotein lipase activity in adipose tissue and skeletal muscle may have reduced the uptake and oxidation of fatty acids derived from exogenous lipids.

Studies of the long-term regulation of hepatic pyruvate dehydrogenase kinase.

The administration of a low-carbohydrate/high-saturated-fat (LC/HF) diet for 28 days or starvation for 48 h both increased pyruvate dehydrogenase kinase (PDHK) activity in extracts of rat hepatic mitochondria, by approx. 2.1-fold and 3.5-fold respectively. ELISAs of extracts of hepatic mitochondria, conducted over a range of pyruvate dehydrogenase (PDH) activities, revealed that mitochondrial immunoreactive PDHKII (the major PDHK isoform in rat liver) was significantly increased by approx. 1.4-fold after 28 days of LC/HF feeding and by approx. 2-fold after 48 h of starvation. The effect of LC/HF feeding to increase hepatic PDHK activity was retained through hepatocyte preparation, but was decreased on 21 h culture with insulin (100 micro-i.u./ml). A sustained (24 h) 2-4-fold elevation in plasma insulin concentration in vivo (achieved by insulin infusion via an osmotic pump) suppressed the effect of LC/HF feeding so that hepatic PDHK activities did not differ significantly from those of (insulin-infused) control rats. The increase in hepatic PDHK activity evoked by 28 days of LC/HF feeding was prevented and reversed (within 24 h) by the replacement of 7% of the dietary lipid with long-chain omega-3 fatty acids. Analysis of hepatic membrane lipid revealed a 1.9-fold increase in the ratio of total polyunsaturated omega-3 fatty acids to total mono-unsaturated fatty acids. The results indicate that the increased hepatic PDHK activities observed in livers of LC/HF-fed or 48 h-starved rats are associated with long-term actions to increase hepatic PDHKII concentrations. The long-term regulation of hepatic PDHK by LC/HF feeding might be achieved through an impaired action of insulin to suppress PDHK activity. In addition, the fatty acid composition of the diet, rather than the fat content, is a key influence.

Molecular mechanisms underlying the long-term impact of dietary fat to increase cardiac pyruvate dehydrogenase kinase: regulation by insulin, cyclic AMP and pyruvate.

Previous studies have demonstrated that pyruvate dehydrogenase kinase (PDHK) activity in extracts of rat cardiac mitochondria is increased @two-fold by providing a high-fat diet for 28 days. The present study sought to establish the factor(s) that might underlie the response of cardiac PDHK to the provision of a high-fat diet. ELISA assays of PDHKII, conducted over a range of PDHK activities, demonstrated that the increase in cardiac PDHK activity was not due to an increase in mitochondrial immunoreactive PDHKII concentration. The pyruvate concentration giving 50% active PDHC (PDHa) in mitochondria incubated with respiratory substrates was unaffected by high-fat feeding, demonstrating a dissociation between increased PDHK activity and altered sensitivity of PDHK to suppression by pyruvate. In cardiac myocytes cultured (25 h) with n-octanoate (1 mm) plus dibutyryl cAMP (50 microM), insulin at 12.5 microU/ml, 25 microU/ml and 75 microU/ml, suppressed PDHK activities in cells prepared from control rats, but insulin at concentrations <100 microU/ml failed to suppress PDHK activities in cardiac myocytes prepared from high-fat-fed rats. In vivo, cardiac insulin sensitivity (assessed by euglycaemic hyperinsulinaemic clamp in combination with 2-[3H] deoxyglucose administration) was suppressed after high-fat feeding. A sustained (24 h) two- to four-fold elevation in plasma insulin concentration (achieved by insulin infusion via osmotic pumps) did not affect PDHK activity in hearts of control rats. In contrast, PDHK activity in hearts of high-fat-fed rats was suppressed to values not significantly different from (insulin-infused) control rats. Basal and agonist-stimulated cAMP concentrations were unaffected by high-fat-feeding or insulin. Furthermore, rates of palmitate oxidation (to CO2) in cardiac myocytes (in the absence or presence of insulin or adrenergic agonists) were not statistically significantly affected by high-fat-feeding. The results indicate that an impaired action of insulin to suppress PDHK participates in the mechanism by which increased PDHK activity is achieved in response to high-fat feeding, but insulin does not act through decreasing cAMP concentrations or suppressing fatty acid oxidation.

Perinatal nutrition enriched with omega-3 polyunsaturated fatty acids attenuates endotoxic shock in newborn rats.

Sepsis and septic shock continue to have a high mortality and morbidity in the newborn. Eicosanoids are important mediators in Gram negative septic shock. Omega-3 polyunsaturated fatty acids (omega-3) decrease production of biologically active 2-series eicosanoids. Therefore, we hypothesized that omega-3-enriched diet could decrease 2-series eicosanoids and attenuate endotoxic shock in newborn rats. Sprague-Dawley rat dams were fed with either omega-3 polyunsaturated fatty acid-enriched diet (omega-3 PURA) or omega-6 polyunsaturated fatty acid enriched diet (omega-6PUFA; controls) from the 16th day of gestation until 10 days after parturition. In 10 day old rats, shock was induced by an intraperitoneal injection of Salmonella enteritidis lipopolysaccharide. The omega-3PUFA decreased the mortality of endotoxic shock. In omega-6PUFA, lipopolysaccharide induced hyperglycemia at 2 h and hypoglycemia thereafter without an elevation in plasma insulin concentration, omega-3PUFA attenuated the hyperglycemia and hypoglycemia. omega-3PUFA attenuated the decrease of liver phosphoenolpyruvate ca-boxykinase mRNA abundance, suggesting preserved gluconeogenesis. Therefore, perinatal feeding with omega-3PUFA was beneficial in attenuating glucose dyshomeostasis in newborn rats with endotoxic shock and may be a novel approach to the prevention of endotoxic shock in the newborn.

Relation of angiographically defined coronary artery disease and plasma concentrations of insulin, lipid, and apolipoprotein in normolipidemic subjects with varying degrees of glucose tolerance

We investigated the association between hyperinsulinemia ana changes in lipid, lipoprotein, and apolipoprotein that would increase the risk of coronary artery disease (CAD) independent of glucose tolerance. A coronary angiogram was recorded in 127 male subjects, including 41 with normal glucose tolerance, 41 with impaired glucose tolerance, and 45 with non-insulin-dependent diabetes mellitus (NIDDM). Subjects were divided info 2 groups according to results: the group with CAD (n = 94) and the group with normal coronary arteries (n = 33). All subjects were normolipidemic (total cholesterol <230 mg/dl and triglycerides <150 mg/dl). The CAD group had a significantly lower plasma level of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apo A-I) and a higher level of apolipoprotein B (apo B) than the normal group with normal glucose tolerance. In considering subjects with impaired glucose tolerance or NIDDM, the CAD group had a significantly lower plasma level of HDL cholesterol and apo A-I and a significantly higher plasma level of total cholesterol, triglycerides, and apo B than the normal group. In each of the subjects with normal and impaired glucose tolerance, and NIDDM, the elevation of plasma insulin concentration during both the complete test period and the early phase of an oral glucose challenge was significantly higher in the CAD than in the normal group. In all subjects, graded reductions in HDL cholesterol and apo A-I and graded increases in plasma total cholesterol, triglycerides, and apo B were observed with increasing tertiles of the postglucose challenge measurements of insulinemia. Multivariate analysis of the data confirmed the independent effect of plasma levels of apo A-I and apo B on the severity of CAD. Thus, hyperinsulinemia appeared to be associated with changes in lipid and apolipoprotein that predisposed toward coronary atherosclerosis not only in nondiabetic subjects, but also in those with impaired glucose tolerance and NIDDM. The plasma levels of both apo A-I and apo B, both nontraditional risk factors, were better predictors of CAD than were plasma levels of lipids in normolipidemic men.

The role of insulin resistance and hyperinsulinemia in coronary heart disease

Patients with impaired glucose tolerance (IGT) and non-insulin-dependent diabetes mellitus (NIDDM) are more resistant to insulin-stimulated glucose uptake than are individuals with normal glucose tolerance. Evidence has also been published showing that first-degree relatives of patients with NIDDM are insulin resistant when compared with a matched group of relatives of subjects with normal glucose tolerance. In addition, the ability of insulin to stimulate glucose uptake varies approximately fourfold in individuals with normal glucose tolerance, and insulin resistance of a degree comparable to that seen in patients with IGT or with Type II diabetes is present in a significant portion of the normal population. Given a defect in insulin-stimulated glucose uptake, glucose tolerance can only be maintained if insulin-resistant individuals continue to secrete greater than normal amounts of insulin. As a corollary, glucose homeostasis will decompensate when the insulin secretory response begins to decrease, and the greater the decline in insulin secretion, the larger the increase in plasma glucose concentration. Resistance to insulin-stimulated glucose uptake and compensatory hyperinsulinemia seems to represent the basic defect in patients with NIDDM, with failure of β-cell function and subsequent development of fasting hyperglycemia only occurring later. This general formulation has received considerable support from longitudinal studies of the natural history of NIDDM. The fact that an increase in ambient insulin concentration can prevent gross decompensation of glucose tolerance in an insulin-resistant individual does not mean that this compensatory response is benign. It now appears that resistance to insulin-stimulated glucose uptake and compensatory hyperinsulinemia are associated not only with states of IGT, but are also seen in individuals with high blood pressure, hypertriglyceridemia, and low plasma concentrations of high-density lipoprotein (HDL) cholesterol. All of these events have been identified as increasing the risk of coronary heart disease (CHD), and there is increasing evidence that they tend to cluster in the same individual. As a consequence, it has been suggested that this constellation of abnormalities constitutes a syndrome (X) that plays an important role in the etiology of CHD. Indeed, in some populations it can be argued that Syndrome X is involved in the etiology of CHD to a greater degree than is an increase in plasma low-density lipoprotein (LDL) cholesterol concentration. In summary, resistance to insulin-stimulated glucose uptake seems to be a relatively common phenomenon, and is present in the majority of patients with IGT or NIDDM. The normal physiologic response to this defect in insulin action is to secrete more insulin in an effort to minimize the degree of IGT. If this compensatory response fails, glucose tolerance decompensates. Unfortunately, even if the hyperinsulinemia can be maintained, such individuals appear to be at increased risk of CHD, either directly as a result of the hyperinsulinemia, or secondary to the increase in blood pressure and the dyslipidemia shown to be associated with resistance to insulin-stimulated glucose uptake and elevation of plasma insulin concentration. As a result of these considerations, it seems possible that insulin resistance plays a major role in several important human diseases.

Effect of Acute Physiological Elevations of Insulin on Circulating Androgen Levels in Nonobese Women*

Extreme pharmacological elevation of the circulating insulin level acutely lowers dehydroepiandrosterone sulfate (DHEAS) levels. To assess whether more physiological elevations in plasma insulin (due to exogenous infusion or endogenous secretion) would have similar effects, we examined the levels of DHEAS, androstenedione, testosterone, and free testosterone before and after euglycemic hyperinsulinemic and hyperglycemic hyperinsulinemic clamp studies. Studies were performed in women within 20% of ideal body weight after an overnight fast. Androgen levels were measured before and at the conclusion of studies in which either insulin was infused exogenously at 1 mU/kg.min or endogenous insulin secretion was stimulated for 2 h by elevation of the plasma glucose concentration by 125 mg/dL above basal levels by an exogenous glucose infusion. Basal plasma DHEAS (6.2 +/- 0.5 mumol/L) declined to 5.2 +/- 0.4 mumol/L (P less than 0.001) during the euglycemic insulin clamp, without any significant change in testosterone, free testosterone, or androstenedione. During the hyperglycemic clamp, DHEAS fell from 6.7 +/- 0.5 to 5.1 +/- 0.4 mumol/L (P less than 0.001) in response to endogenous hyperinsulinemia; plasma testosterone, free testosterone, and androstenedione did not change significantly. There was no correlation between the elevation in plasma insulin concentration and the fall in DHEAS during either the euglycemic or hyperglycemic clamps. However, the magnitude of fall of DHEAS was directly correlated with the initial DHEAS level in both the euglycemic (r = 0.51; P less than 0.05) and hyperglycemic (r = 0.75; P less than 0.01) studies. This association of hyperinsulinemia with a reduction of circulating levels of DHEAS, but not other C-19 steroids (e.g. testosterone and androstenedione) may reflect differential mechanisms by which DHEAS levels are regulated and suggests that insulin either inhibits its biosynthesis and/or secretion, or enhances its MCR.

The central amygdala is involved in the conditioned but not in the meal-induced cephalic insulin response in the rat

The central nucleus of the amygdala (CEA) is considered to be involved in the regulation of autonomic correlates of fear. Its involvement in the control of autonomic functions other than elicited by fear has received little attention. The effects of a bilateral electrolytical lesion of the CEA on feeding related insulin responses have been analyzed in male Wistar rats. The cephalic phase of the insulin response is a vagally mediated elevation of plasma insulin concentration during the first minute after meal onset, before any increase in plasma glucose can be noticed. This response can also be entrained to environmental stimuli. The insulin response elicited under these conditions is due to conditioning. CEA lesioning abolished the conditioned insulin response but not the early insulin elevation during the presentation of food. The CEA lesion failed to affect plasma glucose levels in both the meal-induced and conditioned test situations. To our knowledge this is the first study that shows that the CEA is also involved in the organization of conditioned metabolic endocrine responses.

Effects of insulin on kidney function and sodium excretion in healthy subjects.

Insulin action on kidney function was evaluated in 8 healthy subjects, (mean age 27 years) using the euglycaemic clamp technique. Insulin was infused at rates of 0, 20 and 40 mU.min-1.m-2 over consecutive periods of 120 min resulting in plasma insulin concentrations of 8 +/- 2, 29 +/- 7 and 66 +/- 14 mU/l. The renal clearance of 51Cr-EDTA, lithium, sodium and potassium was determined during the last 90 min of each period. Sodium clearance declined with increasing plasma insulin concentrations (1.3 +/- 0.4, 1.0 +/- 0.3 and 0.5 +/- 0.2 ml.min-1.1.73 m-2, p less than 0.001), while glomerular filtration rate (108 +/- 21, 104 +/- 21 and 108 +/- 20 ml.min-1. 1.73 m-2) and lithium clearance (a marker of fluid flow rate from the proximal tubules) 29 +/- 5, 29 +/- 4 and 30 +/- 4 ml.min-1.1.73 m-2) remained unchanged. Calculated proximal tubular reabsorption of sodium and water was unchanged, while calculated distal fractional sodium reabsorption increased (95.5 +/- 1.5, 96.4 +/- 1.2 and 98.1 +/- 0.7%, p less than 0.001). Potassium clearance and plasma potassium concentration declined, whereas plasma aldosterone and plasma renin concentrations were unchanged. In conclusion, elevation of plasma insulin concentration within the physiological range has a marked antinatriuretic action. This effect is located distally to the proximal renal tubules.

Augmentation of secretagogue‐induced amylase secretion in pancreatic acini of heat‐exposed rats.

1. The effects of prolonged heat exposure on pancreatic exocrine secretion were investigated to evaluate the involvement of the insulin-pancreatic acinar axis. Rats were kept at 34 degrees C and a relative humidity of 40% for 2 weeks with or without insulin administration. Control rats were housed at the thermoneutral temperature of 25 degrees C. By using isolated acini, secretory function was examined at the cellular level. 2. Without insulin treatment, acinar amylase concentration, expressed per microgram of cellular protein, was increased by heat exposure, while trypsinogen concentration, expressed per microgram of acinar DNA, decreased. The ratio of acinar amylase to trypsinogen increased significantly from 2.82 to 5.69 by prolonged heat exposure. With insulin treatment, the heat-induced increase in amylase activity was lessened but the decrease in trypsinogen remained unchanged. The ratio was somewhat lessened to 4.66. 3. In acini from saline-treated rats, amylase release in response to varying concentrations of cholecystokinin octapeptide or carbamylcholine was significantly augmented by prolonged heat exposure. As a result, the dose-response curve shifted upwards. However, in acini from insulin-treated rats, the increase in secretory response was lessened, similar to the effect on acinar content. On the other hand, changes in trypsinogen release were not as notable as those in amylase release. The ratio of amylase to trypsinogen in pancreatic juice released by 100 pM-cholecystokinin octapeptide increased from 1.56 to 3.04 in saline-treated rats and from 1.60 to 2.34 in insulin-treated rats. 4. In heat-exposed, saline-treated rats the plasma concentrations of glucose and insulin were significantly elevated, while in insulin-treated rats these increases were lessened and the elevation of plasma insulin concentration was no longer significant. 5. It is suggested that heat exposure elevates resting plasma glucose concentration, probably because of decreased metabolic activity, which results in a concomitant rise in plasma insulin concentration. This hormonal change most likely is a major cause of augmentation of acinar amylase synthesis and of the resultant potentiation of stimulus-secretion coupling via an insulin-pancreatic acinar axis. Heat exposure modified pancreatic exocrine function in the opposite direction to what occurred in cold-exposed animals. It was confirmed that changes in pancreatic exocrine function via a modification of the insulin-pancreatic acinar axis can actually occur under normal physiological circumstances. From the nutritional point of view, this modification by ambient temperature should be taken into consideration.

Quantitation of insulin-stimulated glucose disposal in patients with non-insulin-dependent diabetes mellitus.

Glucose disposal rates (Rd) during an insulin clamp study reflect both basal and insulin-stimulated Rd. To quantify the amount of glucose taken up in response to a known increase in insulin concentration, two consecutive studies were performed on 10 patients with mild to moderate NIDDM (mean fasting glucose = 146 mg/dl) and 10 normal subjects. Endogenous insulin secretion was inhibited by somatostatin and plasma glucose level maintained at 180 mg/dl for 5. Rd (mg/m2/min) was determined isotopically for 2.5 h at insulin concentrations approximately 6 microU/ml and during 2.5 h of physiologic hyperinsulinemia at approximately 60 microU/ml (total glucose disposal), with the increase in Rd resulting from the approximate 10-fold elevation of plasma insulin concentration defined as insulin-stimulated glucose disposal. Results showed that the increment in Rd resulting from the elevation of plasma insulin concentration was relatively minor in NIDDM (38 +/- 6), increasing from a mean (+/- SEM) value of 83 +/- 8 to 121 +/- 12. Similar values in normal subjects were 90 +/- 7 and 274 +/- 26 with an increment of 183 +/- 21. Thus, insulin-stimulated glucose uptake in patients with NIDDM was only one-fifth of that in normals, and accounted for only 31% (38 divided by 121) of total glucose disposal during the clamp study. These data indicate that the majority of previous insulin clamp studies of in vivo insulin action in patients with NIDDM, in which total glucose disposal and insulin-stimulated glucose disposal have been equated, have underestimated the magnitude of insulin resistance present in NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS)

395 HUMAN FETAL AND NEONATAL INSULIN RESPONSE TO MATERNAL HYPERGLYCEMIA AT CESAREAN SECTION (C/S)

The neonatal insulin response to glucose pertubation may be blunted in the normal infant due to a stable glucose milieu in utero. We hypothesized that fetal hyperinsulinemia might be a major factor in subsequent glucose control. We evaluated fetal hyperglycemia following induced maternal hyperglycemia at C/S. Subjects included 16 non-diabetic mothers who had a repeat elective C/S under spinal anesthesia at 39.9±0.2 wks (M±SEM). All received a bolus (757±42ml) of Ringers Lactate (RL) (n=7) or RL 5% Dextrose (n=9) for 20.6±0.8 min. prior to delivery to prevent hypotension. Blood was sampled prior to infusion (MAT I) and at delivery (MAT II) and from infants via the umbilical vein (UV)and artery (UA) and for 4 hours after birthAll mothers and infants receiving glucose had marked hyperglycemia and hyperinsulinemia at delivery. Neonatal hyperinsulinemia subsided rapidly as plasma glucose concentration fell. No infant developed hypoglycemia after 30 min., probably related to counter-regulatory mechanisms in the newborn. We conclude that the normal term infant can respond to an exogenous glucose load with immediate elevation of plasma insulin concentration.