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Background & Aims: Dietary polyphenols have beneficial effects on glucose/lipid metabolism in subjects at high risk to develop type 2 diabetes; however, the underlying mechanisms are not clear. We aimed to evaluate: 1) the acute effects of the consumption of a drink rich in polyphenols from red grape pomace (RGPD) on glucose/insulin and triglyceride responses to a standard meal in healthy individuals, and, 2) the relationship between plasma levels of phenolic metabolites and metabolic parameters., Methods: Twelve healthy men, aged 20-40 years participated in a randomized, controlled study according to a cross-over design. After a 3-day low-polyphenol diet, all participants consumed, on two different days and separated by a one week interval, after an overnight fast, a drink rich in polyphenols (1.562 g gallic acid equivalents (GAE)) or a control drink (CD, no polyphenols), followed after 3 h by a standard meal (960 kcal, 18% protein, 30% fat, 52% CHO). Blood samples were taken at fasting, 3 h after the drink, over 5 h after the standard meal and at fasting on the next day to measure plasma concentrations of glucose, insulin, triglyceride and phenolic metabolites., Results: Glycemic and triglyceride post-meal responses were similar after both the RGPD and the control drink. In contrast, postprandial insulin incremental area (iAUC 0-5h ) was 31% lower (p < 0.05), insulin secretion index was 18% lower (p < 0.016) and insulin sensitivity (S I ) index was 36% higher (p = 0.037) after the RGPD compared to CD. Among phenolic metabolites, gallic acid correlated inversely with the insulin response (r = -0.604; p = 0.032) and positively with the S I index (r = 0.588, p = 0.037)., Conclusions: RGPD consumption acutely reduced postprandial insulin levels and improved insulin sensitivity. This effect could be likely related to the increase in gallic acid levels. This drink, added to usual diet, could contribute to increase the daily intake of polyphenols, with potential health benefits. CLINICALTRIALS., Gov Identifier: NCT02865278., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objective: To evaluate the impact of high-glycaemic index and low-glycaemic index meals on postprandial blood glucose in patients with Type 1 diabetes treated with continuous subcutaneous insulin infusion., Methods: Sixteen patients with Type 1 diabetes under continuous subcutaneous insulin infusion treatment, age 36±0.5 years (mean±sem), HbA(1c) 7.6±0.2% (56±1.1 mmol/mol), consumed two test meals with an identical macronutrient composition, but with a different glycaemic index: 59 vs. 90. Blood glucose was checked before the test meal and every 30 min thereafter for 180 min. The same preprandial insulin dose was administered on the two occasions., Results: Blood glucose concentrations following the low-glycaemic index meal were significantly lower than those of the high-glycaemic index meal (P<0.05 to P<0.01). The blood glucose area under the curve after the low-glycaemic index meal was 20% lower than after the high-glycaemic meal (P=0.006)., Conclusions:   Our data show that meals with the same carbohydrate content but a different glycaemic index produce clinically significant differences in postprandial blood glucose., (© 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.)

In patients harboring the IR1152 mutant insulin receptor, hepatic glucose production was normally suppressed by insulin. Hepatocytes without the insulin receptor gene and expressing IR1152 (Hep(MUT)) also showed normal insulin suppression of glucose production and full insulin response of glycogen synthase. In contrast, expression of the IR1152 mutant in skeletal muscle maximally increased glucose uptake and storage, preventing further insulin stimulation. IRS-1 phosphorylation was normally stimulated by insulin in both intact Hep(MUT) and L6 skeletal muscle cells expressing the IR1152 mutant (L6(MUT)). At variance, IRS-2 phosphorylation exhibited high basal levels with no further insulin-dependent increase in L6(MUT) but almost normal phosphorylation, both basal and insulin-stimulated, in the Hep(MUT) cells. In vitro, IR1152 mutant preparations from both the L6(MUT) and the Hep(MUT) cells exhibited increased basal and no insulin-stimulated phosphorylation of IRS-2 immobilized from either muscle or liver cells. IR1152 internalization in liver and muscle cells closely paralleled the ability of this mutant to phosphorylate IRS-2 in vivo in these cells. Block of receptor internalization (wild-type and mutant) in the liver and muscle cells also inhibited IRS-2, but not IRS-1, phosphorylation. Thus, the mechanisms controlling insulin receptor internalization differ in liver and skeletal muscle cells and may enable IR1152 to control glucose metabolism selectively in liver. In both cell types, receptor internalization seems necessary for IRS-2 but not IRS-1 phosphorylation.

To evaluate the predictive factors of insulin requirement in newly diagnosed patients with unclassifiable diabetes, 54 consecutive patients, aged less than 35 years, were prospectively followed for 3 years or more. At entry, haemoglobin HbA1c, basal and stimulated C-peptide concentrations, HLA phenotype, islet cell antibodies (ICA) status, and serum levels of soluble CD8 antigen (sCD8) were evaluated. After a median time of 9 (range 2-32) months, 31 patients (group 1) required insulin therapy, whereas 23 patients (group 2) remained non-insulin-requiring after 36 months. Group 1 patients were younger (P < 0.05) and had higher HbA1c and sCD8 serum levels (P < 0.0001), respectively), a higher frequency of ICA positivity and of HLA DR3 and/or DR4 phenotype (P < 0.005 and P < 0.0001, respectively), and lower C-peptide concentrations (P < 0.005 and P < 0.0001, basal and stimulated, respectively) than group 2. The sensitivity, specificity, positive and negative predictive value, and overall accuracy for the subsequent insulin requirement were: sCD8 serum levels (> 737 U/ml), 100%, 65%, 79%, 100% and 85%, respectively; stimulated C-peptide (< 0.60 nmol/l), 71%, 96%, 96%, 74% and 81%, respectively; and ICA positivity (> 20 JDFU), 45%, 91%, 87%, 55% and 65%, respectively. Thus, higher sCD8 serum levels, low stimulated C-peptide concentrations and ICA positivity are the most powerful predictors of subsequent recourse to insulin therapy in young, newly detected patients with unclassifiable diabetes.

To determine the role of insulin and free fatty acid (FFA) concentration in the regulation of FFA metabolism, forearm FFA fluxes were quantified in 16 healthy volunteers by combining the forearm perfusion technique with the infusion of [3H]palmitate. Three groups of studies were performed. In study 1 (n = 6), a systemic insulin infusion (1.2 mU/kg.min) was performed for 120 min while euglycemia was maintained by a variable glucose infusion. In Study 2 (n = 5), insulin (0.05 mU/kg.min) was infused into the brachial artery to expose the forearm tissues to the same insulin level as in study 1. In study 3 (n = 5), heparin was infused to raise plasma FFA concentration to 1-1.5 mmol/L. At 60 min, an intrabrachial insulin infusion was added as in study 2 and maintained for 60 min. During systemic insulin infusion, plasma FFA concentration fell to 0.09 +/- 0.02 mmol/L. Forearm FFA uptake (FFA-U) decreased from the basal value of 2.54 +/- 0.52 to 0.95 +/- 0.10 mumol/L.min (P < 0.05). Likewise, forearm FFA release (FFA-R) fell to 1.0 +/- 0.31 mumol/L.min (P < 0.05). With local insulin administration, both FFA levels and FFA-U remained unchanged, whereas FFA-R was markedly inhibited (from 1.78 +/- 0.23 to 1.04 +/- 0.24 mumol/L.min; P < 0.05). In study 3 (heparin infusion), FFA levels rose to 1.17 +/- 0.12 mmol/L due to a 4-fold increase in FFA-R (from 1.18 +/- 0.36 to 6.92 +/- 2.40 mumol/L.min; P < 0.05). FFA-U rose from the basal value of 2.50 +/- 0.82 to 6.92 +/- 1.95 mumol/L.min (P < 0.05). Addition of intrabrachial insulin did not modify FFA-U, whereas heparin activation of FFA-R was only partially antagonized (4.53 +/- 2.40 mumol/L.min; 0.01 < P < 0.05 vs. heparin alone). The data demonstrate that plasma FFA concentration is the main determinant of forearm FFA transport. Insulin exerts a direct inhibitory effect on FFA release and affects tissue FFA transport only indirectly through the fall in circulating FFA.

To determine whether the anti-insulin effect of epinephrine is due to a direct antagonism on target tissues or is mediated by indirect mechanisms (systemic substrate and/or hormone changes), insulin and epinephrine were infused intrabrachially in five normal volunteers using the forearm perfusion technique. Insulin (2.5 mU/min) was infused alone for 90 minutes and in combination with epinephrine (25 ng/min) for an additional 90 minutes, so as to increase the local concentrations of these hormones to physiological levels (60 to 75 microU/mL and 200 to 250 pg/mL for insulin and epinephrine, respectively). Systemic plasma glucose and free fatty acids (FFA) concentrations remained stable at their basal values during local hormone infusion. Forearm glucose uptake (FGU) increased in response to insulin alone from 0.8 +/- 0.2 mg.L-1.min-1 to 4.3 +/- 0.8. Addition of epinephrine completely abolished the insulin effect on FGU, which returned to its preinfusion value (0.7 +/- 0.2). Forearm lactate release was slightly increased by insulin alone, but rose markedly on addition of epinephrine (from 5.2 +/- 0.8 mumol.L-1.min-1 to 17 +/- 2; P less than .02). During infusion of insulin alone, forearm FFA release (FFR) decreased significantly from the postabsorptive value of 1.76 +/- 0.25 mumol.L-1.min-1 to 1.05 +/- 0.11 (P less than .01). Epinephrine addition reverted insulin suppression of FFR, which returned to values slightly above baseline (2.06 +/- 0.47 mumol.L-1.min-1; P less than .05 v insulin alone). The data demonstrate that epinephrine is able to antagonize directly insulin action on forearm tissues with respect to both stimulation of glucose uptake and inhibition of FFA mobilization.

The reason why hyperinsulinemia is associated with essential hypertension is not known. To test the hypothesis of a pathophysiologic link mediated by the sympathetic nervous system, we measured the changes in forearm norepinephrine release, by using the forearm perfusion technique in conjunction with the infusion of tritiated NE, in patients with essential hypertension and in normal subjects receiving insulin intravenously (1 mU/kg per min) while maintaining euglycemia. Hyperinsulinemia (50-60 microU/ml in the deep forearm vein) evoked a significant increase in forearm NE release in both groups of subjects. However, the response of hypertensives was threefold greater compared to that of normotensives (2.28 +/- 45 ng.liter-1.min-1 in hypertensives and 0.80 +/- 0.27 ng.liter-1 in normals; P less than 0.01). Forearm glucose uptake rose to 5.1 +/- .7 mg.liter-1.min-1 in response to insulin in hypertensives and to 7.9 +/- 1.3 mg.liter-1.min-1 in normotensives (P less than 0.05). To clarify whether insulin action was due to a direct effect on muscle NE metabolism, in another set of experiments insulin was infused locally into the brachial artery to expose only the forearm tissues to the same insulin levels as in the systemic studies. During local hyperinsulinemia, forearm NE release remained virtually unchanged both in hypertensive and in normal subjects. Furthermore, forearm glucose disposal was activated to a similar extent in both groups (5.0 +/- 0.6 and 5.2 +/- 1.1 mg.liter-1.min-1 in hypertensives and in normals, respectively). These data demonstrate that: (a) insulin evokes an abnormal muscle sympathetic overactivity in essential hypertension which is mediated by mechanisms involving the central nervous system; and (b) insulin resistance associated with hypertension is demonstrable in the skeletal muscle tissue only with systemic insulin administration which produces muscle sympathetic overactivity. The data fit the hypothesis that the sympathetic system mediates the pathophysiologic link between hyperinsulinemia and essential hypertension.

To determine whether insulin action on human skeletal muscle is entirely accounted for by a direct effect of insulin per se, we quantitated forearm glucose uptake (FGU) in two groups of normal subjects under conditions of identical forearm tissue insulinization (approximately 90 microU/ml) induced by means of systemic (group I) or intrabrachial insulin infusion (group II). With this approach, a difference of FGU between the two groups is demonstrative of the operation of indirect mechanisms in insulin action. During insulin infusion in group I, euglycemia was maintained by a variable glucose infusion, whereas arterial free fatty acid (FFA) concentration fell below 0.1 mM. In group II, arterial concentrations of both glucose and FFA remained unchanged, indicating that insulin effect was indeed restricted to the forearm tissues. With local insulin administration, FGU reached levels approximately 40% lower than those achieved with systemic insulin infusion (P less than 0.01-0.005). To determine whether this difference could be attributed to the fall in FFA concentration associated with systemic insulinization, FGU was also quantitated during a systemic insulin plus heparin infusion (group III) to maintain FFA at their basal levels. In this condition, insulin-stimulated FGU was not different from that observed in group I. These data demonstrate that 1) insulin action on skeletal muscle glucose disposal is mediated by a direct as well as an indirect component, and 2) the maintenance of basal FFA does not affect insulin-stimulated FGU, indicating that the indirect component of insulin action is mediated by a different mechanism.

We evaluated whether the increased peripheral insulin sensitivity often reported after physical exercise is generalized or limited to the active musculature. Substrate exchange in leg (previously active) and forearm (previously inactive) were measured by catheterization technique basally and during a hyperinsulinaemic euglycaemic clamp (2 mU insulin kg-1 BW min-1) in nine healthy men before and 1 day after 3-h exercise (50% VO2max). One day after exercise basal glucose uptake was unchanged in the leg, while it was decreased in the forearm (-61%, P less than 0.01) compared with the pre-exercise condition. Glucose uptake during hyperinsulinaemia was increased in the leg (+31%, P less than 0.05), but not in the forearm. Basal lactate release by the leg was increased by the exercise, while lactate release by the forearm was decreased, significantly only during the clamp. These results indicate that local and not systemic factors are responsible for the changes in insulin sensitivity observed in the recovery from physical exercise.

To determine the contribution of skeletal muscle to fasting hyperglycemia in noninsulin dependent type II diabetes (NIDDM), the forearm balance of glucose, lactate, and alanine was quantified in 25 control subjects, 21 hyperglycemic (blood glucose: 11.6 mmol/L), and 19 insulin-treated patients with NIDDM (blood glucose: 5.8 mmol/L). Forearm glucose uptake was similar in controls (4.6 +/- 0.6 mumol L-1 min-1) and in hyperglycemic diabetic patients (4.5 +/- 0.9 mumol L-1 min-1). In spite of this, in the diabetic patients lactate (5.1 +/- 0.8 mumol L-1 min-1) and alanine (2.6 +/- 0.4) release by the forearm was 3- and 2-fold higher than in the control group (lactate: 1.7 +/- 0.8, P less than 0.005; and alanine: 1.3 +/- 0.2, P less than 0.05, respectively). The ratio of lactate release to glucose uptake was 57% and 18% in diabetic and control subjects, respectively. Insulin administration did not affect either glucose uptake or the release of gluconeogenic substrates by the forearm. It is concluded that: 1) in fasting patients with NIDDM, glucose is taken up by the skeletal muscle in normal amounts but preferentially used nonoxidatively with lactate formation. This suggests that, although the muscle does not contribute directly to fasting hyperglycemia, it may play an indirect role through an increased delivery of glucose precursors; and 2) insulin-induced normoglycemia is maintained by mechanisms that do not involve the exchange of glucose and gluconeogenic substrates by the skeletal muscle.

Sixty-four unrelated healthy subjects were studied for the detection of a DNA polymorphism at the 5' end of the insulin gene. No significant difference between the groups was found in blood glucose values at fasting and after an oral glucose load. A significant association was found between fasting (P less than 0.05) and after load plasma C-peptide levels (P less than 0.01) and the presence of a 1.6 Kb insertion at the 5' end of the insulin gene. A gene dose-dependent effect was noted, class 3/3 individuals having the lowest after-load C-peptide concentration and class 1/3 an intermediate level (F for the linear trend: P = 0.007). This might suggest that insulin gene polymorphism affects insulin secretion in healthy individuals. In order to confirm this, a subgroup of six class 3/3 and eight class 1/1 individuals subsequently underwent a hyperglycaemic clamp. The tissue sensitivity to insulin was similar in the two groups but glucose-stimulated insulin secretion was markedly impaired in homozygotes for the class 3 allele. In this group, insulin secretion was, on average, only one-third of that in class 1/1 individuals (P less than 0.02). Similarly impaired in class 3/3 persons was the glucose + arginine-stimulated insulin secretion (P less than 0.05). We conclude that the polymorphism at the 5' end of the insulin gene is associated with variations in insulin secretion in healthy humans.

Certain acute and chronic metabolic effects of nicardipine have been studied in 20 patients with non-insulin dependent diabetes (NIDD). An intravenous glucose tolerance test (i.v. GTT, glucose 0.33 g/kg as a bolus) and the corresponding insulin response were assessed at the end of a 4 week placebo period, after the first dose and on administration for 12 weeks of nicardipine 20 mg t.i.d. The glucose and insulin responses to the i.v.GTT, evaluated as incremental AUCs, did not change significantly (glucose 30.5 mg/dl.90 min on placebo, 33.1 mg/dl.90 min acutely and 31.4 mg/dl.90 min on chronic administration of nicardipine; insulin 2.08 microU/ml.90 min on placebo, 1.87 microU/ml.90 min acutely and 1.93 microU/ml.90 min after chronic nicardipine). Glucose removal rate (KG) following the i.v.GTT was 0.73%/min on placebo 0.75%/min on acute administration and 0.8%.min-1 with chronic nicardipine. Active treatment produced a significant reduction of blood pressure (from 187/96 mm Hg on placebo to 166/89 mm Hg acutely and 152/83 mm Hg after 12 weeks of nicardipine treatment). It is concluded that the calcium antagonist nicardipine was an effective antihypertensive drug, and that it did not cause deterioration of metabolic control in hypertensive patients with NIDD.

Twenty-four hour plasma free insulin and blood glucose and intermediary metabolite profiles have been measured in 6 C-peptide deficient 'brittle' diabetic patients, during continuous sc and im insulin infusion. During sc infusion free insulin profiles were erratic and unpredictable. Mean 24 h blood glucose levels were raised at 12.6 +/- 2.1 (SE) mmol/l, and 3-hydroxybutyrate at 0.24 +/- 0.08 mmol/l. Blood lactate (1.88 +/- 0.18 mmol/l) and glycerol (0.084 +/- 0.007) were also elevated. Insulin (im) restored free insulin profiles to the normal pattern as found in 'stable' diabetics on sc infusion, with characteristic post-meal peaks (49 +/- 7, 103 +/- 35, and 95 +/- 34 mU/l) and stable night-time levels. Mean 24 h blood glucose was 6.7 +/- 1.1 mmol/l (P less than 0-.05 compared to sc infusion) and 3-hydroxybutyrate 0.07 +/- 0.02 mmol/l (P less than 0.05). Blood lactate (1.67 +/- 0.08 mmol/l) and glycerol (0.10 +/- 0.02 mmol/l) levels remained abnormal. The ratio of plasma free insulin to insulin dose administered was significantly higher during im infusion. In the 6 'stable' diabetics on sc insulin infusion good blood glucose control (7.1 +/- 0.9 mmol/l) was accompanied by clear post-prandial insulin peaks, and stable nocturnal levels. The results strongly suggest that in one category of 'brittle' diabetics there is defective and erratic sc insulin absorption.

The effects of 3 weeks of treatment with the beta-receptor blocking agent propranolol and a placebo on glucose tolerance, insulin secretion and peripheral insulin sensitivity have been evaluated in 7 normoglycaemic hypertensive patients by an oral glucose tolerance test and the insulin clamp technique. Significant changes in systolic and diastolic blood pressure and heart rate were observed at the end of propranolol treatment, but there were no associated changes in glucose tolerance, insulin secretion or peripheral insulin sensitivity. No difference was observed in glucagon, growth hormone and free fatty acids between propranolol and placebo treatment. The results support the view that the hypothetical pancreatic glucoreceptor, at least in non-acute studies, is not affected by beta blockade. In addition, there was no effect on tissue sensitivity to insulin.

The effects of beta-blockers on glucose tolerance, insulin secretion and peripheral insulin sensitivity were evaluated by oral glucose tolerance test and euglycaemic insulin technique in six normoglycaemic patients with primary arterial hypertension at the end of 3-week treatments with placebo (one tablet twice daily) and propranolol (80 mg twice daily). Body weight did not change during the study (83 kg at the end of placebo, 83 kg at the end of propranolol), while blood pressure (150 +/- 9/97 +/- 8 mmHg on placebo, 138 +/- 8/89 +/- 8 mmHg on propranolol, P < 0.01) and heart rate (66 +/- 9 beats/min on placebo, 60 +/- 5 beats/min on propranolol, P < 0.05) showed a significant fall on the beta-blocker. No change was observed in glucose tolerance (incremental area for glucose 3462 +/- 1149 mg/dl per min on placebo, 3209 +/- 1695 mg/dl per min on propranolol), insulin secretion (incremental area for serum insulin 7579 +/- 4380 microU/ml per min on placebo, 7934 +/- 4351 microU/ml per min on propranolol) and peripheral insulin sensitivity (metabolic clearance rate 11 +/- 4 ml/kg per min on placebo, 13 +/- 6 ml/kg per min on propranolol). These data support the hypothesis that chronic treatment with adrenergic blocking agents does not induce any significant change in insulin secretion or peripheral insulin sensitivity.

Ten insulin-dependent C-peptide-negative diabetic subjects, whose control had been optimized on twice-daily injection therapy, were treated for periods of 10 wk in a crossover study, with either a thrice-daily subcutaneous insulin injection regimen (Actrapid + Ultratard) or by continuous subcutaneous insulin infusion (CSII). On CSII insulin dose stabilized at 51 +/- 5 U/day, compared with 80 +/- 9 U/day (P = 0.004) on the thrice-daily injection regimen, having been 60 +/- 6 U/day on twice-daily therapy. After 10 wk glycosylated hemoglobin was 11.7 +/- 0.6% on injection therapy and 10.0 +/- 0.7% (P = 0.026) on CSII. Mean blood glucose concentration and urinary glucose excretion were lower at most points during the study on CSII than on injection therapy. Patients on pumps gained weight compared with the thrice-daily injection regimen (P = 0.023 at 10 wk) and the previous twice-daily regimen, despite the reduction in insulin dose. Considering individual patients, four markedly improved on CSII compared with the previous twice-daily regimen and five compared with Actrapid + Ultratard. No patient showed impaired control on CSII compared with either injection regimen. The benefits of portable insulin infusion pumps over injection therapy are thus clearly demonstrable under outpatient conditions even with equal and intensive medical attention.

Although it has been reported that bezafibrate influences carbohydrate metabolism, this possibility has never been properly evaluated in a controlled clinical trial. In this study we attempted to evaluate the effects of bezafibrate on plasma lipoproteins, glucose tolerance, insulin secretion and peripheral insulin sensitivity in a group of hypertriglyceridemic patients with and without diabetes. Sixteen hyperlipidemic patients (10 males and 6 females) participated in the study. Eight had type IIB and 8 type IV hyperlipoproteinemia; 6 of them also had non-insulin dependent diabetes mellitus. The study was performed according to a double blind, crossover design: after 1 month wash-out period in which patients were on diet alone, they underwent, in a random order, a period of placebo therapy and another period in which they received a single daily dose of a long-acting bezafibrate preparation (400 mg) administered in the evening. Each treatment lasted 2 months. Total plasma and VLDL triglyceride concentrations were consistently reduced by bezafibrate (-46%, P less than 0.001; and -50%, P less than 0.001). Total and VLDL-cholesterol were also reduced by bezafibrate. The effects of bezafibrate on lipoproteins were similar in diabetic and non-diabetic subjects. Bezafibrate treatment did not influence fasting blood glucose concentration, glucose tolerance, peripheral insulin sensitivity or insulin secretion. In conclusion, the results of this controlled trial clearly indicate that bezafibrate can be successfully employed to lower plasma lipid levels in patients with non-insulin dependent diabetes mellitus and hyperlipidemia.

The activity of biosynthetic human insulin (BHI) has been compared with that of pork insulin using the glucose clamp technique in normal subjects. After a baseline period, insulin was infused at 0.02 U/kg/h for 2 h, then 0.032 U/kg/h for 2 h, and finally 0.05 U/kg/h for 2 h. Glucose was clamped at baseline values using a glucose-controlled insulin infusion system (Biostator) and the amount of glucose infused to maintain normoglycemia calculated for each insulin dose for the two insulins. C-peptide levels decreased with both insulins, suggesting suppression of endogenous insulin secretion. Serum insulin levels attained were the same for both insulins. There were no significant differences in either total glucose infused or glucose infused during the last 30 or 60 min at each insulin dose for the two insulins. Intermediary metabolite responses to the infusion of the two insulins were similar. We conclude that in normal human beings, BHI shows identical metabolic activity with pork insulin.

In order to evaluate the influence of serum insulin levels on serum lipoprotein composition, 62 randomly selected healthy males were studied. All of them had a normal glucose tolerance. The Insulin Response to a bolus of intravenous glucose (0.50 g/kg) was significantly correlated with VLDL-Triglyceride (p less than 0.01), VLDL-Cholesterol (p less than 0.01) and with the "Atherogenic Index" (Formula: see text) (p less than 0.01). Moreover, stratifing the all population in quartiles according to the Insulin Response distribution, the highest quartile had a significant increase in Total and VLDL-Cholesterol levels (p less than 0.02), as well as in Total (p less than 0.02), VLDL (p less than 0.02) and LDL (p less than 0.01) Triglyceride, in comparison with the lowest quartile. The Atherogenic Index was also significantly elevated in the high Insulin Response group (p less than 0.005). The influence of serum insulin on lipoprotein metabolism was also evaluated by a stepwise multiple regression analysis. Body weight, Insulin Response and Exogenous Triglyceride removal were independently correlated with VLDL-Triglyceride concentration (r = 0.58, p less than 0.001). VLDL cholesterol concentration and fasting serum insulin levels were inversely correlated with HDL-Cholesterol (r = 0.49, p less than 0.001). In conclusion, in absence of any metabolic derangement, high insulin levels are associated with multiple lipoprotein abnormalities. Insulin might act as a risk factor for arterial disease through its influence on serum lipoproteins.

The disposal of a mixed meal was examined in 11 male subjects by multiple (splanchnic and femoral) catheterization combined with double-isotope technique (intravenous [2-3H]glucose plus oral U-[14C]starch). Glucose kinetics and organ substrate balance were measured basally and for 5 h after eating pizza (600 kcal) containing carbohydrates 75 g as starch, proteins 37 g, and lipids 17 g. The portal appearance of ingested carbohydrate was maximal (1.0 mmol/min) between 30 and 60 min after the meal and gradually declined thereafter, but was still incomplete at 300 min (0.46+/-0.08 mmol/min). The total amount of glucose absorbed by the gut over the 5 h of the study was 247+/-26 mmol (45+/-6 g), corresponding to 60+/-6% of the ingested starch. Net splanchnic glucose balance (-6.7+/-0.5 micromol x kg(-1) x min(-1), basal) rose by 250-300% between 30 and 60 min and then returned to baseline. Hepatic glucose production (HGP) was suppressed slightly and only tardily in response to meal ingestion (approximately 30% between 120 and 300 min). Splanchnic glucose uptake (3.7+/-0.6 micromol x kg(-1) x min(-1), basal) peaked to 9.8+/-2.0 micromol x kg(-1) x min(-1) (P<0.001) at 120 min and then returned slowly to baseline. Leg glucose uptake (34+/-5 micromol x leg(-1) x min(-1), basal) rose to 151+/-29 micromol x leg(-1) x min(-1) at 30 min (P<0.001) and remained above baseline until the end of the study, despite no increase in leg blood flow. The total amount of glucose taken up by the splanchnic area and total muscle mass was 161+/-16 mmol (29+/-3 g) and 128 mmol (23 g), respectively, which represent 39 and 30% of the ingested starch. Arterial blood lactate increased by 30% after meal ingestion. Net splanchnic lactate balance switched from a basal net uptake (3.2+/-0.6 micromol kg(-1) x min(-1) to a net output between 60 and 120 min and tended to zero thereafter. Leg lactate release (25+/-11 micromol x leg(-1) x min(-1), basal) drastically decreased postprandially. Arterial concentration of both branched-chain amino acids (BCAA) and non-branched-chain amino acids (N-BCAA) increased significantly after meal ingestion (P<0.001). The splanchnic area switched from a basal net amino acid uptake (31+/-16 and 92+/-48 micromol/min for BCAA and N-BCAA, respectively) to a net amino acid release postprandially. The net splanchnic amino acid release over 5 h was 11.3+/-4.2 mmol for BCAA and 37.8+/-9.7 mmol for N-BCAA. Basally, the net leg balance of BCAA was neutral (-3+/-5 micromol x leg(-1) x min(-1)), whereas that of N-BCAA indicated a net release (54+/-14 micromol x leg(-1) x min(-1)). After meal ingestion, there was a net leg uptake of BCAA (20+/-6 micromol x leg(-1) x min(-1)), whereas leg release of N-BCAA decreased by 50%. It is concluded that in human subjects, 1) the absorption of a natural mixed meal is still incomplete at 5 h after ingestion; 2) HGP is only marginally and tardily inhibited; 3) splanchnic and peripheral tissues contribute to the disposal of meal carbohydrate to approximately the same extent; 4) the splanchnic area transfers >30% of the ingested proteins to the systemic circulation; and 5) after meal ingestion, skeletal muscle takes up BCAA to replenish muscle protein stores. [ABSTRACT FROM AUTHOR]