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Biomedical subjects

P Tessari

Publications and source records attributed to P Tessari.

At least 19 recordsLinked to original sources
PubMed2006

Diabetic nephropathy is associated with increased albumin and fibrinogen production in patients with type 2 diabetes.

AIMS/HYPOTHESIS: Hyperfibrinogenaemia and albuminuria are cardiovascular risk factors, often coexisting in diabetic and non-diabetic people. Albuminuria in turn is associated with a compensatory albumin overproduction in non-diabetic patients. It is not known whether the presence of albuminuria in patients with type 2 diabetes mellitus is associated with greater albumin and fibrinogen production rates than in normoalbuminuric patients. SUBJECTS, MATERIALS, AND METHODS: Using leucine isotope methods, we measured fractional and absolute synthesis rates (FSR, ASR) of albumin and fibrinogen in post-absorptive type 2 diabetic patients with either normal (n=11) or increased (n=10) urinary albumin excretion. RESULTS: In albuminuric patients, albumin FSR (16.2+/-1.5%/day) and ASR (20.5+/-1.9 g/day) were greater (p<0.02 and p<0.05, respectively) than in normoalbuminuric patients (FSR=11.5+/-1.1%/day; ASR=15.7+/-1.2 g/day). Fibrinogen FSR was similar between patients with normal and increased albumin excretion, but concentration, the circulating pool and ASR of fibrinogen were 40 to 50% greater (p<0.035) in patients with albuminuria. Albuminuria was positively correlated with albumin ASR, with fibrinogen concentration, the fibrinogen pool and ASR, whereas albumin synthesis was inversely correlated with calculated oncotic pressure. CONCLUSIONS/INTERPRETATION: Synthesis of albumin and fibrinogen is upregulated in type 2 diabetic patients with increased urinary albumin excretion. Albuminuria is associated with enhanced fibrinogen and albumin synthesis.

Albuminuria↗
PubMed2002

Impairment of albumin and whole body postprandial protein synthesis in compensated liver cirrhosis.

To investigate the anabolic effects of feeding in cirrhosis, we measured albumin fractional synthesis rate (FSR) and whole body protein synthesis in six nondiabetic patients with stable liver cirrhosis (three in the Child-Pugh classification Class A, three in Class B) and in seven normal control subjects, before and after administration of a 4-h mixed meal. Leucine tracer precursor-product relationships and whole body kinetics were employed at steady state. Basal levels of postabsorptive albumin concentration and FSR, whole body leucine rate of appearance, oxidation, and nonoxidative leucine disposal (NOLD, approximately equal to protein synthesis) were similar in the two groups. However, after the meal, in the patients neither albumin FSR (from 8.5 +/- 1.5 to 8.8 +/- 1.8 %/day) nor NOLD (from 1.69 +/- 0.22 to 1.55 +/- 0.26 micromol x kg(-1) x min(-1)) changed (P = nonsignificant vs. basal), whereas they increased in control subjects (albumin FSR: from 10.9 +/- 1.5 to 15.9 +/- 1.9 %/day, P < 0.002; NOLD: from 1.80 +/- 0.14 to 2.10 +/- 0.19 micromol x kg(-1) x min(-1), P = 0.032). Thus mixed meal ingestion did not stimulate either albumin FSR or whole body protein synthesis in compensated liver cirrhosis. The mechanism(s) maintaining normoalbuminemia at this disease stage need to be further investigated.

Adult↗
PubMed2001

Insulin infusion normalizes fasting and post-prandial albumin and fibrinogen synthesis in Type 1 diabetes mellitus.

AIMS: The effect of metabolic control on hepatic synthesis of plasma proteins in Type 1 diabetes mellitus (T1DM), in the post-absorptive and post-prandial state, is not known. METHODS: We measured fractional synthetic rates (FSR) of albumin and fibrinogen in six insulin-infused T1DM patients and in five to nine control subjects, before and for approx. 4 h after a mixed liquid meal. Phenylalanine tracer precursor/product relationships and steady-state conditions were used. In the post-absorptive state, patients were studied in near euglycaemic conditions after an overnight intravenous insulin infusion. During the meal (approx. 11 kcal/kg), the insulin infusion rate was increased to maintain plasma glucose concentrations below approx. 10 mmol/l. RESULTS: Post-absorptive FSR of albumin (5.7 +/- 0.6%/day) and fibrinogen (11.3 +/- 0.6%/day) in T1DM were similar to control values (6.4 +/- 0.9 and 13.1 +/- 1.1, respectively). After the meal, albumin FSR increased (P = 0.0032 by anova) in both groups (T1DM, to 14.4 +/- 2.7%/day; controls, to 18.2 +/- 3.7%/day). Fibrinogen FSR also increased (P = 0.0048 by anova) in both the T1DM (to 18.2 +/- 2.6) and the control subjects (to 27.3 +/- 6.2). There was no difference between T1DM and control subjects in the post-prandial FSR of both proteins. CONCLUSIONS: Albumin and fibrinogen FSR in T1DM can be maintained within near-normal ranges by insulin infusion under post-absorptive and post-prandial conditions.

Adult↗
PubMed2001

Plasma protein synthesis in patients with low-grade nephrotic proteinuria.

Overt nephrotic syndrome is characterized by albumin and fibrinogen hyperproduction and reduced very low density lipoprotein apolipoprotein B-100 (VLDL apoB-100) clearance. Whether similar changes also occur in low-grade proteinuria is not known. Thus we measured albumin, fibrinogen, and VLDL apoB-100 kinetics in six patients with modest proteinuria and normal creatinine clearance (P) and in ten control subjects (C) by leucine tracer infusion and precursor-product relationships. In P, plasma albumin concentration was decreased (P < 0.003), whereas concentrations of fibrinogen and VLDL apoB-100 were increased (P < 0.001). In P, albumin fractional secretion rate (FSR) was increased (P < 0.01), fibrinogen FSR was normal, and VLDL apoB-100 FSR was decreased (P < 0.03). As a result, in P, absolute secretion rates (ASR) of albumin and fibrinogen were increased (P < 0.03), whereas VLDL apoB-100 ASR was normal. Albumin FSR was inversely correlated to oncotic pressure in P but not in C. These findings suggest that low-grade nephrotic proteinuria is characterized by simultaneous multiple alterations in turnover rates of albumin, fibrinogen, and VLDL apoB-100. Their pathogenesis, however, appears to be multifactorial.

Adult↗
PubMed2001

Glucose kinetics and splanchnic uptake following mixed meal ingestion in cirrhotic-diabetic subjects.

Although glucose intolerance and/or overt diabetes are common in cirrhotic subjects, the mechanism(s) that lead to post-prandial hyperglycemia in cirrhosis are not entirely known. To this aim, we measured whole-body rates of glucose appearance (Ra) and of disappearance (Rd) in cirrhotic-diabetic subjects and in controls, before and following a 4-hr administration of a mixed meal. In the post-prandial phase, endogenous and dietary glucose Ra, as well as first-pass splanchnic uptake of dietary glucose, were measured using a double (ie oral and intravenous) glucose tracer technique. In the fasting state, the cirrhotic patients were hyperglycemic (12.0 +/- 1.4 vs 4.4 +/- 0.2 mmol/l in controls, p < 0.001), had a higher glucose Ra (17.0 +/- 2.7 vs 10.2 +/- 0.5 micromol x kg(-1) x min(-1), p < 0.05) and a lower clearance rate (1.51 +/- 0.19 vs 2.32 +/- 0.06 ml x kg x min, p < 0.02). Following the meal, plasma glucose increased to greater values (p < 0.002) in the patients (to 16.8 +/- 2 mmol/l, mean values of the last 40 min) than in the controls (to 7.2 +/- 0.4 mmol/l). Insulin increased in both groups but it was 35% lower (p > 0.05) in the patients. Post-prandial total glucose Ra (cirrhotics: 21.3 +/- 2.6; controls: 19.2 +/- 1.4 pmol x kg(-1) x min(-1)), endogenous Ra (cirrhotics: 7.3 +/- 1.5; controls: 7.0 +/- 1.3 micromol x kg(-1) x min(-1)) and first-pass splanchnic uptake of dietary glucose (cirrhotics: 9.8 +/- 2.6; controls: 11.5 +/- 1.6 micromol x kg x min(-1)), were not different between the 2 groups, whereas glucose clearance remained lower (p<0.001) in the patients (1.31 +/- 0.25 ml x kg(-1) x min)-1)) than in the controls (2.72 +/- 0.26). These data demonstrate that, in cirrhotic-diabetic patients, post-pran-dial hyperglycemia is not due to a reduced extraction of dietary glucose nor to an increased endogenous production, but rather to a defect in peripheral glucose clearance, secondary to either insulin-resistance and/or relative insulin deficiency.

Adult↗
PubMed2000

Role of insulin in age-related changes in macronutrient metabolism.

Age is associated with an increase in body fat mass and a decrease of protein mass. As body substrate turnover is under insulin control, defects in insulin secretion and/or action may in part account for these changes. As regards secretion, current evidence suggest that no clear defect in insulin secretion is found in the aged. The wide spectrum of glucose tolerance of the elderly may be associated with different patterns of insulin secretion. Insulin sensitivity to glucose metabolism is more or less normal in the aged, despite subtle delays in the onset of its action. Normalization of the data by either body weight or lean body mass is important in defining the insulin sensitivity of the elderly. Increased rates of free fatty acid (FFA) flux and oxidation rates have been found in healthy elderly subjects, both when post-absorptive and during hyperinsulinemia. These differences however disappeared following normalization by fat mass, suggesting that FFA kinetics reflect the established changes in fat mass. Thus, the mechanism(s) leading to an increase in the fat mass in elderly cannot simply be derived from studies of fat kinetics. The operation of the Randle cycle (ie, inverse relationships between fat and glucose oxidation) in the elderly has also been suggested. Finally, the insulin effects on whole-body amino acid and protein metabolism do not seem to be impaired in the aged. However, in the human muscle a decreased synthesis of contractile as well as mitochondrial proteins was found, in association with decreased specific gene expression. The degree of physical activity probably interacts with these changes, possibly playing a causative role. The possible interaction between insulin and exercise in the maintenance of muscle mass in the elderly needs to be studied further.

Aging↗
PubMed2000

Interorgan amino acid exchange.

This review is concerned with the status of our current research related to the exchange of amino acids across organs. Accumulation of knowledge regarding how amino acid pools are maintained within the body remains a work in progress. In recent years, the use of organ balance measurement techniques in combination with isotopic tracers has much increased our understanding of the role of the kidney and splanchnic organs in amino acid metabolism, and in kidney and liver gluconeogenesis from amino acids. An interorgan cooperation between the kidney and splanchnic organs for leucine-ketoisocaproate metabolism has also been demonstrated.

Amino Acids↗
PubMed2000

Changes in protein, carbohydrate, and fat metabolism with aging: possible role of insulin.

Age is associated with modifications of body composition, i.e., an increase in body fat mass and a decrease in protein mass. Because insulin controls substrate disposal and production, these changes could theoretically be related to changes in either insulin action or secretion on the various substrates. On the basis of available evidence, insulin action on whole-body amino acid and protein metabolism seems not to be impaired in the aged. Decreased synthesis of contractile and mitochondrial proteins in muscle, associated with decreased gene expression, was described in humans. Decreased physical activity apparently represents an important factor responsible for decreased muscle protein synthesis and mass in the elderly. Exercise in the elderly may acutely revert these changes, although its chronic effects are still uncertain. In addition, the possible interaction between insulin and exercise in the maintenance of muscle mass needs to be specifically investigated in aged people. Higher free fatty acid (FFA) absolute flux and oxidation rates were observed in healthy elderly subjects in both the fasting state and following hyperinsulinemia, but not when normalized over fat mass. This suggests that FFA kinetics reflect the established changes in fat mass. Insulin sensitivity on glucose metabolism is usually normal in the aged, despite subtle impairments in insulin secretion, hepatic uptake, and onset of action. Finally, data support the operation of the Randle cycle (i.e., inverse relationships between fat and glucose oxidation) in the elderly.

Aging↗
PubMed2000

Increased fibrinogen production in type 2 diabetic patients without detectable vascular complications: correlation with plasma glucagon concentrations.

Fibrinogen is a strong cardiovascular risk factor in the general population, and increased fibrinogen plasma concentrations have been reported in type 2 diabetic patients. However, the mechanisms leading to hyperfibrinogenemia in type 2 diabetes are not known. It is also not known whether possible alterations of fibrinogen turnover may precede clinical diabetic micro- and macrovascular complications and therefore potentially contribute to their onset. To address these questions, fibrinogen production was determined in six male type 2 diabetic patients without detectable micro- and macrovascular complications (age, 45 +/- 4 yr; body mass index, 27 +/- 0.9 kg/m2) and in seven nondiabetic matched controls using leucine isotope precursor-product relationships. Plasma glucose (P < 0.001), insulin (P < 0.05), and glucagon concentrations (P < 0.01) were increased in the patients. Diabetic patients also had increased plasma fibrinogen concentration (+ approximately 50%; P < 0.01) and pool (+ approximately 40%; P < 0.01) as well as fractional (+ approximately 35%; P = 0.08) and absolute (+ approximately 100%; P < 0.01) synthetic rates. The plasma glucagon concentration was positively related (P < 0.005 or less) to the fibrinogen concentration as well as to fractional and absolute synthetic rates. Thus, fibrinogen production is markedly enhanced, and this alteration is likely to determine the observed hyperfibrinogenemia in type 2 diabetic patients. Hyperglucagonemia may contribute to the increased fibrinogen production. These findings in normoalbuminuric patients without clinical complications support the hypothesis that increased fibrinogen production and plasma concentrations may precede and possibly contribute to the onset of clinical cardiovascular complications in type 2 diabetes.

Adult↗
PubMed1999

Protein metabolism in glucagonoma.

Although protein wasting and reduced amino acid concentrations are common findings in glucagonoma patients, the mechanisms underlying these alterations are unclear. Therefore, we studied basal postabsorptive leucine, phenylalanine and tyrosine turnover following L-[D3]-Leucine, L-[D5]-Phenylalanine and L-[D2]-Tyrosine i.v. infusions in one male and one female patient with glucagonoma, compared with healthy control volunteers. Plasma amino acid concentrations were reduced (-40 to 80%, delta >2 SD vs. control subjects) in both patients. Plasma leucine, phenylalanine and tyrosine rates of appearance in patients with glucagonoma were similar to values in the control subjects, except leucine rate of appearence in the female patient with glucagonoma (+ approximately 30%, delta >2 SD). In contrast, the intracellular leucine rate of appearence, reflecting protein degradation, was considerably increased in both patients (+60-80%, delta >2 SD). Phenylalanine hydroxylation was moderately higher only in the male patient with glucagonoma (+ approximately 30%, delta >2 SD). Leucine, phenylalanine and tyrosine clearances (+100-300%), as well as phenylalanine hydroxylative clearance (+75-100%) were also increased in the patients. In conclusion, whole-body protein breakdown is enhanced in patients with glucagonoma compared with healthy control subjects. Phenylalanine hydroxylative clearance is also higher. Reduced plasma amino acid concentrations are probably due, at least in part, to their increased clearance. These alterations could contribute to the determination of the catabolic state of the glucagonoma syndrome.

Adult↗
PubMed1999

Differences in estimates of forearm protein synthesis between leucine and phenylalanine tracers following unbalanced amino acid infusion.

We compared the leucine (Leu) and phenylalanine (Phe) tracer-determined response of forearm protein synthesis (PS) before and after stimulation of protein anabolism by intravenous infusion of Leu-enriched, Phe-deficient amino acids and insulin (increased to approximately 100 microU/mL) with the euglycemic clamp. Six healthy subjects received primed-constant infusions of L-[ring-2H5]-Phe and L-[1-(14)C]-Leu, and steady-state forearm Phe and Leu kinetics were determined. Following the combined infusion, the arterial Leu concentration increased approximately 70% (P < .001), whereas Phe decreased about 15% (P < .01). Forearm PS and net balance (NB) increased (P < .05 or less v basal) using both amino acid tracers. However, the relative increments observed with the Leu tracer were more than 75% larger (P < .05 or less) than those observed with the Phe tracer, even when the data were corrected for the standard relative abundance of these two amino acids in forearm protein(s). Thus, the calculated changes of forearm PS and NB in response to an unbalanced amino acid infusion with hyperinsulinemia were affected by the plasma level of leucine and phenylalanine, whose tracers were used to estimate forearm protein turnover. Since these two essential amino acids share the same transport system, a competition at this level cannot be excluded.

Adult↗
PubMed1999

Phenylalanine hydroxylation across the kidney in humans rapid communication.

UNLABELLED: Phenylalanine hydroxylation across the kidney in humans. BACKGROUND: Although phenylalanine hydroxylase activity is detectable in in vitro renal tissue preparations, no data on in vivo phenylalanine hydroxylation across the human kidney, as well as on its possible contribution to whole-body hydroxylation, currently exist. METHODS: To this aim, we have measured whole-body, renal, and splanchnic phenylalanine hydroxylation to tyrosine, as well as phenylalanine and tyrosine rates of appearance (Ra) and disposal (Rd), in postabsorptive subjects by means of renal and splanchnic arteriovenous catheterization combined with phenylalanine and tyrosine isotope infusions. RESULTS: In the kidney, a relevant phenylalanine hydroxylation activity was detected (3.51 +/- 0.97 micromol/min x 1.73 m2 of body surface), whereas it was 2.48 +/- 1. 35 micromol/min x 1.73 m2 across the splanchnic area. These two sites together accounted for virtually the entire whole-body phenylalanine hydroxylation. Renal production of tyrosine from phenylalanine hydroxylation accounted for approximately 13% of whole-body tyrosine Ra, whereas renal total tyrosine Ra accounted for approximately 34% of whole-body tyrosine Ra. In the splanchnic area, these figures were approximately 9 and 40%, respectively. Hydroxylation accounted for approximately 70% of phenylalanine Rd in the kidney, as opposed to approximately 8% in the splanchnic area. CONCLUSIONS: These data indicate that hydroxylation represents the major route of phenylalanine disposal within the kidney. The kidney and the splanchnic bed together account for all of the whole-body phenylalanine hydroxylation. These data also provide a further explanation for the reduced tyrosine pools occurring in uremia.

Adult↗
PubMed1999

Effects of branched-chain-enriched amino acids and insulin on forearm leucine kinetics.

Although amino acid mixtures enriched in branched-chain amino acids (BCAA) and deficient in aromatic amino acids (AAA) are often used together with insulin and glucose in clinical nutrition, their physiological effects on muscle protein anabolism are not known. To this aim, we studied forearm leucine kinetics in post-absorptive volunteers, before and after the systemic infusion of BCAA-enriched, AAA-deficient amino acids along with insulin and the euglycaemic clamp. The results were compared with the effects of insulin infusion alone. A compartmental leucine forearm model was employed at steady state. Hyperaminoacidaemia with hyperinsulinaemia (to approximately 80-100 micro-units/ml) increased the leucine plasma concentration (+70%; P<0.001), inflow into the forearm cell (+150%; P<0.01), disposal into protein synthesis (+100%; P<0.01), net intracellular retention (P<0.01), net forearm balance (by approximately 6-fold; P<0.01) and net deamination to alpha-ketoisocaproate (4-methyl-2-oxopentanoate) (+9%; P<0.05). Leucine release from forearm proteolysis and outflow from the forearm cell were unchanged. In contrast, hyperinsulinaemia alone decreased plasma leucine concentrations (-35%; P<0.001) and leucine inflow (-20%; P<0.05) and outflow (-30%; P<0.01) into and out of forearm cell(s), it increased net intracellular leucine retention (P<0.03), and it did not change leucine release from forearm proteolysis (-20%; P=0.138), net leucine deamination to alpha-ketoisocaproate, leucine disposal into protein synthesis or net forearm protein balance. By considering all data together, leucine disposal into protein synthesis was directly correlated with leucine inflow into the cell (r=0.71; P<0.0001). These data indicate that the infusion of BCAA-enriched, AAA-deficient amino acids along with insulin is capable of stimulating forearm (i.e. muscle) protein anabolism in normal volunteers by enhancing intracellular leucine transport and protein synthesis. These effects are probably due to hyperaminoacidaemia and/or its interaction with hyperinsulinaemia, since they were not observed under conditions of hyperinsulinaemia alone.

Adult↗
PubMed1998

Relationships between phenylalanine hydroxylation and plasma aromatic amino acid concentrations in humans.

We investigated the relationships between phenylalanine hydroxylation (Phe Hy) and plasma concentrations of phenylalanine, tyrosine, and glucagon in healthy male volunteers (N = 13; age, 29 +/- 3 years). Phe Hy, as well as the Phe and Tyr rate of appearance (Ra), were measured during L-[2H5]-Phe and L-[2H2]-Tyr continuous intravenous (i.v.) infusions both under basal postabsorptive conditions (N = 13) and following divergent changes of plasma aromatic amino acids (AAA) concentrations. Namely, AAA were increased by administration of a balanced synthetic mixed meal (n = 6) or selectively decreased by i.v. infusion of insulin along with a Phe-deficient, Tyr and tryptophan-deprived amino acid mixture ([IAA] n = 7). Following the meal, plasma Phe (54 +/- 3 to 81 +/- 12 micromol/L), plasma Tyr (54 +/- 4 to 91 +/- 7), Phe Hy (0.09 +/- 0.01 to 0.15 +/- 0.02 micromol/kg x min), Phe Ra (0.65 +/- 0.04 to 0.96 +/- 0.07), and Tyr Ra (0.51 +/- 0.03 to 0.93 +/- 0.11) all significantly increased (P < or = .05 v basal). IAA infusion significantly decreased plasma Phe (to 47 +/- 3 micromol/L), plasma Tyr (to 25 +/- 4), Phe Hy (to 0.07 +/- 0.004 micromol/kg x min), and Tyr Ra (to 0.29 +/- 0.02; all P < or = .05 v sal), while Phe Ra did not change (0.64 +/- 0.04, NS). Plasma glucagon did not change in the three experimental periods (basal, 85 +/- 7; meal, 72 +/- 10; IAA, 92 +/- 14 pg/mL; NS). Using linear regression analysis, plasma Phe was positively related to both Phe Hy (R2 = .76, P < .001) and plasma Tyr (R2 = .80, P < .001); Phe Hy and plasma Tyr were also significantly correlated (R2 = .60, P < .001). No correlation was found between Phe Hy and basal plasma glucagon (R2 = .04, NS). Using multiple regression analysis with plasma Tyr as the dependent variable, plasma Phe was still correlation with plasma Tyr (t = 4.29, P = .0002), while the relationship between Phe Hy and plasma Tyr was no longer significant (t = 0.69, P = .49). These data indicate that plasma Phe is closely associated with its own hydroxylative disposal in humans, and confirm that Phe conversion to Tyr may play a physiological role in maintaining balanced plasma phenylalanine and tyrosine concentrations.

Adult↗
PubMed1997

Splanchnic versus whole-body production of alpha-ketoisocaproate from leucine in the fed state.

The extent to which dietary branched-chain amino acids are deaminated by the splanchnic tissues (ie, the liver and gut) in the fed state and released as ketoacids into the systemic circulation is not known. To determine this, we combined the oral (L-[1-13C]-leucine, [13C]-Leu) and intravenous (L-[5,5,5-2H3]leucine, [2H3]-Leu) leucine tracer infusion with the intravenous administration of an independent isotope of the leucine ketoanalog alpha-ketoisocaproic acid (KIC) ([4,5-3H]KIC). The study was conducted during constant administration of a complete mixed meal. We found that 26% +/- 5% of the orally administered leucine was taken up by the splanchnic organs at first pass, whereas 74% +/- 5% appeared in the systemic circulation. The rate of splanchnic KIC release from deamination of dietary leucine accounted for 3% +/- 0.2% of the oral leucine administration rate and 13% +/- 2% of leucine splanchnic uptake (fractional splanchnic deamination). The fraction of whole-body total leucine uptake that was deaminated to KIC was 41% +/- 5% (P < .05 v fractional splanchnic deamination of dietary leucine uptake). We conclude that (1) the release of KIC from leucine deamination within splanchnic tissues constitutes a minimal fraction of first-pass dietary leucine uptake, and (2) splanchnic tissues are relatively less efficient than the whole body in KIC production from leucine deamination.

Adult↗