C-peptide: a redundant relative of insulin?
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C-Peptide↗
Biomedical subjects
L Luzi
Publications and source records attributed to L Luzi.
Simple measures to monitor beta-cell mass and assess islet graft dysfunction.
The aim of this study was to develop a simple test for the assessment of islet graft dysfunction based on measures involving fasting C-peptide. Calculations were made to account for the dependence of C-peptide secretion on glucose concentration (C-peptide/glucose ratio [CP/G]) and adjusted for renal function by calculating the C-peptide/glucose-creatinine ratio (CP/GCr). Values from 22 recipients were analyzed at different times post-last islet infusion. Receiver operating characteristic curves were used to determine which of these measures best predicts high 90-minute glucose (90 min-Glc; >10 mmol/L) after a Mixed Meal Tolerance Test (MMTT). In this initial analysis, CP/G was found to be superior predicting high 90 min-Glc with a larger area under the ROC curve than C-peptide (p = 0.01) and CP/GCr (p = 0.06). We then correlated C-peptide and CP/G with islet equivalents--IEQ/kg infused, 90 min-Glc after MMTT and clinical outcome (beta-score). C-peptide and CP/G in the first 3 months post-last islet infusion correlated with IEQ/kg infused. CP/G correlated with 90 min-Glc and beta-score. C-peptide and CP/G are good indicators of islet mass transplanted. CP/G is more indicative of graft dysfunction and clinical outcome than C-peptide alone. The ease of calculation and the good correlation with other tests makes this ratio a practical tool when monitoring and managing islet transplant recipients.
Adult↗
Increased serum resistin in elite endurance athletes with high insulin sensitivity.
AIMS/HYPOTHESIS: Resistin is an adipokine associated with obesity and type 2 diabetes in animal models, but in humans its role remains uncertain. This study was undertaken to test whether serum resistin is related to insulin resistance and markers of low-grade inflammation in elite athletes taken as a model of extreme insulin sensitivity. SUBJECTS MATERIALS AND METHODS: In 23 elite athletes (sprinters, middle-distance and marathon runners) and in 72 sedentary men including lean and obese individuals with NGT, and obese individuals with IGT or new-onset type 2 diabetes, we assessed insulin sensitivity using a whole-body insulin-sensitivity index (WBISI) derived from a 3-h OGTT; energy homeostasis was also assessed by means of indirect calorimetry, along with circulating adipokines and low-grade pro-inflammatory cyto-chemokines. RESULTS: Professional athletes had increased WBISIs (p<0.001) and lipid oxidation (p<0.03); they also showed higher serum resistin concentrations (p<0.001), although the pro-inflammatory chemokines were not increased in comparison with the other study groups. Resistin was independently associated only with fasting plasma NEFA. Increased resistin was detected in the middle-distance and marathon runners, but not in the sprinters when compared with the lean, young, sedentary individuals. CONCLUSIONS/INTERPRETATION: Serum resistin concentration is increased in elite athletes, providing evidence against the notion that resistin levels reflect insulin resistance in humans, as seen in animal studies. Increased resistin was observed in aerobic-endurance, but not sustained-power athletes and this feature appeared to be independently associated with parameters of fatty acid metabolism.
Adiponectin↗
Increased clonogenic potential of circulating endothelial progenitor cells in patients with type 1 diabetes and proliferative retinopathy.
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Adult↗
Cytoplasmic localization of NPM in myeloid leukemias is dictated by gain-of-function mutations that create a functional nuclear export signal.
Nucleophosmin (NPM) is a nucleus-cytoplasmic shuttling protein that is implicated in centrosome duplication, cell cycle progression and stress response. At the steady state, NPM localizes mainly in the nucleolus, where it forms a complex with different cellular proteins. One-third of acute myeloid leukemias (AML) are characterized by aberrant cytoplasmic localization of NPM, due to mutations within its last coding exon (exon 12) that cause a frameshift and the formation of novel C-termini. We report here our investigations on the molecular basis for the aberrant localization of mutated NPM. Alignment of the C-terminus of the various NPM mutants revealed the obligatory presence of four amino-acid residues that match a CRM1-dependent nuclear export signal (NES). Single alanine-substitutions at these sites provoked nuclear re-localization, while fusion of the mutated C-terminus to a heterologous nuclear protein induced CRM1-dependent cytoplasmic localization. Molecular characterization of one exceptional AML carrying cytoplasmic NPM and germ line exon 12 revealed a somatic mutation in the splicing donor site of exon 9 that caused the formation of a functional NES. It appears, therefore, that AMLs are frequently characterized by gain-of-function mutations of NPM that create functional NES, suggesting that alterations of nuclear export might represent a general mechanism of leukemogenesis and a novel target for therapeutic intervention.
Acute Disease↗
Reduced intrahepatic fat content is associated with increased whole-body lipid oxidation in patients with type 1 diabetes.
AIMS/HYPOTHESIS: Insulin resistance may be associated with ectopic fat accumulation potentially determined by reduced lipid oxidation. In patients with type 1 diabetes peripheral insulin resistance is associated with higher intramyocellular lipid content. We assessed whether these patients are also characterised by intrahepatic fat accumulation and abnormal fat oxidation. METHODS: Nineteen patients with type 1 diabetes (6 women, 13 men, age 35+/-7 years, BMI 23+/-3 kg/m2), HbA1c 8.7+/-1.4%) and 19 healthy matched individuals were studied by (1) euglycaemic-hyperinsulinaemic clamp combined with [6,6-2H2]glucose infusion to assess whole-body glucose metabolism; (2) indirect calorimetry to assess glucose and lipid oxidation; and (3) localised 1H-magnetic resonance spectroscopy of the liver to assess intrahepatic fat content. RESULTS: Patients with type 1 diabetes showed a reduced insulin-stimulated metabolic clearance rate of glucose (4.3+/-1.3 ml kg(-1) min(-1)) in comparison with normal subjects (6.0+/-1.6 ml kg(-1) min(-1); p<0.001). Endogenous glucose production was higher in diabetic patients (p=0.001) and its suppression was impaired during insulin administration (66+/-30 vs 92+/-8%; p=0.047) in comparison with normal subjects. Plasma glucagon concentrations were not different between groups. The estimated hepatic insulin concentration was lower in diabetic patients than in normal subjects (p<0.05), as was the intrahepatic fat content (1.5+/-0.7% and 2.2+/-1.0% respectively; p<0.03), the latter in association with a reduced respiratory quotient (0.74+/-0.05 vs 0.84+/-0.06; p=0.01) and increased fasting lipid oxidation (1.5+/-0.5 vs 0.8+/-0.4 mg kg(-1) min(-1); p<0.01). CONCLUSIONS/INTERPRETATION: In patients with type 1 diabetes, insulin resistance was not associated with increased intrahepatic fat accumulation. In fact, diabetic patients had reduced intrahepatic fat content, which was associated with increased fasting lipid oxidation. The unbalanced hepatic glucagon and insulin concentrations affecting patients with type 1 diabetes may be involved in this abnormality of intrahepatic lipid metabolism.
Adiponectin↗
Reduced whole-body lipid oxidation is associated with insulin resistance, but not with intramyocellular lipid content in offspring of type 2 diabetic patients.
AIMS/HYPOTHESIS: Intramyocellular lipid accumulation and insulin resistance are thought to be due to reduced lipid oxidation in a human model of high risk of developing type 2 diabetes. METHODS: We studied 32 offspring of type 2 diabetic parents and 32 control individuals by means of DXA, indirect calorimetry, insulin clamp and 1H MRS of the calf muscles, and differences between and within study groups were analysed before and after segregation by quartiles of fasting lipid oxidation. RESULTS: In comparison with control subjects, the offspring showed impaired insulin sensitivity, which was associated with higher fasting intramyocellular lipid content (Spearman's rho -0.35; p=0.04), but fasting lipid oxidation did not differ between groups (1.21+/-0.46 vs. 1.25+/-0.37 mg.kg(-1) lean body mass per min; p=0.70). Nevertheless, offspring in the lowest quartile of lipid oxidation had the most severe impairment of insulin sensitivity and a strong association was shown between lipid oxidation and insulin sensitivity within quartiles (Spearman's rho 0.47; p=0.01); this was not observed within the control group (Spearman's rho 0.13; p=0.47). Intramyocellular lipid content was not significantly different within quartiles of lipid oxidation in either of the groups. CONCLUSIONS/INTERPRETATION: Insulin sensitivity improved across increasing quartiles of fasting lipid oxidation in the offspring group, but remained constant in the control group, supporting the hypothesis that impaired fat oxidation is a primary pathogenic factor of insulin resistance in people with a genetic background for type 2 diabetes. Despite their association with impaired insulin sensitivity, soleus and tibialis anterior intramyocellular lipid content remained constant across increasing quartiles of fasting lipid oxidation within both groups.
Adiponectin↗
Differential p70S6k and 4E-BP1 regulation by insulin and amino acids in vascular endothelial and smooth muscle cells.
Differential stimulation of vascular endothelial and smooth muscle cells proliferation is responsible for atherosclerotic lesions. Amino acids and insulin modulate p70S6k and 4E-BP1 activity, regulating cell growth and proliferation. We hypothesised that nutritional (amino acids) and hormonal (insulin) signals differently modulate protein anabolism in human vascular endothelial (HUVEC) and smooth muscle (HVSMC) cells. We evaluated p70S6kinase and 4E-BP1 phosphorylation in the two cell types, grown in amino acid-free medium with or without insulin (INS, 100 nM) or/and amino acids mixture (AA, 3 mM) and with the selective addition or deprivation of branched chain amino acids (BCAA, 0.5 mM). INS stimulated p70S6k and 4E-BP1 phosphorylation transiently in HUVEC and persistently in HVSMC. AA and INS+AA stimulated p70S6k and 4E-BP1 phosphorylation persistently in HUVEC and HVSMC. AA, but not BCAA alone or BCAA-deprived AA, induced p70S6k phosphorylation in HUVEC. BCAA deprivation decreased the p70S6k phosphorylation induced by AA with or without insulin in HVSMC. These results show that anabolic stimuli modulate p70S6k and 4E-BP1 activity differently in the two vascular cell types, suggesting that insulin stimulates protein synthesis for a longer time in HUSMC than in HUVEC. We speculate that hyperinsulinaemia frequently associated with atherosclerosis could induce a selective HVSMC proliferation.
Adaptor Proteins, Signal Transducing↗
Evaluation of insulin release and insulin sensitivity through oral glucose tolerance test: differences between NGT, IFG, IGT, and type 2 diabetes mellitus. A cross-sectional and follow-up study.
We evaluated both insulin release (IR) and insulin sensitivity (IS) through a single oral glucose tolerance test (OGTT) (blood samples at 0, 60, 120 min, as routinely performed in Europe) in subjects with normal and abnormal glucose tolerance. The value 1/HOMA was used as an index of IS and deltaI/deltaG at 60 min was used as an index of IR. In preliminary experiments, 1/HOMA correlated with glucose infusion rate (GIR) at euglycaemic insulin clamp (r=0.495) and with insulin sensitivity index (ISI) at LDIGIT (r=0.714). At OGTT with blood samples at 0, 30, 60 and 120 min, insulin levels at 30 min correlated with insulin levels at 60 min (I30 vs. I60, r=0.584) and deltaI/deltaG at 30 and at 60 min correlated (r=0.365). Values of 1/HOMA from 345 subjects with normal glucose tolerance (NGT), 32 with impaired fasting glucose (IFG), 186 with impaired glucose tolerance (IGT) and 72 with type 2 diabetic mellitus were divided into quartiles. For each quartile, mean (+/- SE) and 95% confidence intervals (CI) of deltaI/deltaG at 60 min were calculated, and subjects were represented by plotting IS vs. IR. Plots of NGT, IGT, and type-2 diabetes mellitus described different curves. Values of subjects with IFG, IGT and type 2 diabetes mellitus fell outside the 95% CI of NGT subjects in all quartiles of IS. To validate this finding, 113 morbidly obese subjects (basal OGTT: 55 NGT, 40 IGT, 18 T2DM) who underwent a major reduction of body weight through bariatric surgery received a second OGTT one year after surgery. Glucose tolerance improved in 40 patients, deteriorated in 8, did not change in 65; the new plots were concordant with the new class of glucose tolerance. OGTT can be used to evaluate both IR and IS in subjects with NGT, IFG, IGT, and type 2 diabetes mellitus in population studies and in follow-up studies. IFG, IGT and type 2 diabetes mellitus are characterized by reduced IR compared to IS.
Adult↗
Post-absorptive and insulin-mediated muscle protein metabolism in liver-transplanted patients.
Cirrhotic patients after liver transplantation show a near-normal glucose homeostasis when in stable condition. In contrast, the basal and insulin-mediated whole-body protein metabolism remain altered several years after the graft. To examine whether the persisting defect of protein metabolism was due to the muscle, 7 non-diabetic liver-transplanted patients in stable condition were studied by means of the catheterization of the brachial artery and the deep forearm vein (to measure the balance across the forearm) and the infusion of labelled leucine and phenylalanine associated with indirect calorimetry. Whole-body proteolysis (as determined by endogenous leucine flux, ELF), protein synthesis (from non-oxidative leucine disposal, NOLD) and leucine oxidation (LO) were reduced in comparison to previously obtained values in a normal population. Insulin infusion (while maintaining euglycemia) induced a not significant variation of forearm phenylalanine Ra (24.4-->16.5 micromol/100 ml forearm min(-1); proteolysis) and Rd (18.5-->19.7; protein synthesis). In contrast, the whole-body insulin-dependent inhibitions of ELF (31.5-->21.8 micromol/m(2) min) and NOLD (27.3-->18.4) were impaired with respect to a normal population. On the basis of the present results, we conclude that skeletal muscle is not responsible for the alterations of leucine metabolism persisting after liver transplantation. By exclusion, this points to the liver as the major determinant of the leucine metabolism defect.
Forearm↗
De novo diabetes in solid organ transplantation.
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Age Factors↗
Portal vs central glucose sensing in humans: the value of clinical models.
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Animals↗
Prediction of the long-term metabolic success of the pancreatic graft function.
BACKGROUND: Strategies to prevent the return to the diabetic state for graft loss or failure or any other cause after pancreas transplantation require the identification of the subjects at risk. This study evaluated whether daily glucose, insulin, and c-peptide profiles and studies of insulin sensitivity and secretion after transplantation predict pancreatic graft failure. METHODS: Fifty-three subjects with type 1 diabetes with end-stage renal failure who received a combined pancreas and kidney transplant underwent the following procedures 1 year after transplantation: 1-day metabolic profiles, sampling every 2 hours for plasma glucose, serum insulin, and c-peptide (n=51); an intravenous glucose tolerance test (IVGTT) to evaluate insulin secretion (n=48); and an euglycemic insulin clamp to evaluate insulin sensitivity (M value, n=14). The recipients were then followed up to 8 years (mean follow-up 4.8+/-0.3 years) to evaluate the return to the diabetic state. RESULTS: Survival analysis showed that plasma glucose in the profiles and insulin secretion in IVGTT were strongly related to the risk of returning to the diabetic state. A cutoff value of mean daily plasma glucose >127 mg/dL, corresponding to the top quartile of the mean plasma glucose distribution in the profiles, predicted the return to the diabetic state within 4 years from transplantation with a 93% specificity and a 100% sensitivity. A cutoff value of insulin delta peak <32 microU/ml in the IVGTT predicted the return to the diabetic state within 4 years from transplantation with a 75% specificity and a 75% sensitivity. In contrast, the M value in the clamp was devoid of predictive value. CONCLUSIONS: This study indicates that the mean 24-h plasma glucose 1 year after transplantation is the strongest predictor of the return to the diabetic state. The risk is related to defects in insulin secretion and not to insulin resistance. Metabolic profiles can be used to screen the subjects at risk to strictly monitor the graft function and to investigate early determinants of graft failure.
Adult↗
The tripartite motif family identifies cell compartments.
A functional genomic approach, based on systematic data gathering, was used to characterize a family of proteins containing a tripartite motif (TRIM). A total of 37 TRIM genes/proteins were studied, 21 of which were novel. The results demonstrate that TRIM proteins share a common function: by means of homo-multimerization they identify specific cell compartments.
Amino Acid Motifs↗
Effects of insulin and amino acids on leucine metabolism in young and middle-aged humans.
BACKGROUND: Aging is characterized by loss of muscle mass. In healthy subjects this process is associated with hormone and nutritional changes which take place over many decades. Aim of the study To investigate the effects of insulin and amino acids on amino acid metabolism in middle-aged humans. METHODS: We evaluated leucine kinetics by means of the intravenous infusion of [1-(14C)]leucine, in 8 young (age 24 +/- 2 yr, BMI 21+/- 2 kg/M2) and in 6 middle-aged (age 53 +/- 4 yr, BMI 26 +/- 1 kg/M2) healthy subjects. Studies were performed under fasting conditions (basal), and after 180 min of euglycemic hyperinsulinemic clamp (study I), or 180 min of euglycemic hyperinsulinemia in combination with an intravenous amino acid infusion (study II). RESULTS: In the basal state endogenous leucine flux (ELF, an index of proteolysis), normalized for IBW, averaged 1.71 +/- 0.12 and 1.66 +/- 0.14 micromol/kg x min in young and middle-aged subjects, respectively. Basal leucine oxidation (0.22 +/- 0.03 vs 0.28 +/- 0.03 micromol/ kg x min, p < 0.05) was lower in middle-aged with respect to young subjects. Non-oxidative leucine disposal (NOLD, an index of protein synthesis: 1.44 +/- 0.11 vs 1.43 +/- 0.11 micromol/kg x min) was similar in young and middle-aged subjects, respectively. In response to insulin (study I) the absolute and percent decline of ELF and LOX were similar in young and middle-aged subjects: ELF declined to 1.05 +/- 0.06 micromol/kg x min (-39 +/- 5 %) and 1.07 +/- 0.14 micromol/kg x min (-36 +/- 4%), in young and middle-aged, respectively (both p < 0.01 vs basal); LOX declined to 0.21 +/- 0.02 micromol/kg min (-35 +/- 3 %), and 0.18 +/- 0.05 micromol/kg x min (-28 +/- 3%, p < 0.05 vs basal) in young and middle-aged individuals respectively (both p < 0.01 vs basal). In contrast, insulin-mediated whole-body glucose uptake was lower in middle-aged subjects (6.6 +/- 1.4 mg/ kg x min) with respect to young individuals (8.1+/-1.7 mg/kg min, p < 0.05). During study II (insulin plus AA) a significant rise in NOLD was obtained in both young (1.72 +/- 0.10 micromol/kg x min, p < 0.01 vs basal) and middle-aged subjects (1.76 +/- 0.25 micromol/kg x min, p < 0.01 vs basal). Similarly, net leucine balance rose significantly in both young (+0.62 +/- 0.13 vs -0.25 +/- 0.02 micromol/kg x min, p < 0.01 vs basal) and middle-aged subjects (+0.37 +/- 0.08 vs -0.22 +/- 0.03 micromol/ kg x min, p < 0.01 vs basal) suggesting that the anabolic response to amino acids is preserved in middle-aged subjects. CONCLUSIONS: In middle-aged subjects we observed 1) a moderate decline in basal leucine oxidation; 2) a normal antiproteolytic response to insulin and a reduction in glucose uptake; and 3) a normal anabolic response to AA plus insulin. In conclusion, the data provide evidence for a normal regulation of protein anabolism and an early dissociation between the metabolic effects of insulin on glucose uptake and proteolysis in middle-aged subjects.
Adult↗
Incorporation of the fasting plasma FFA concentration into QUICKI improves its association with insulin sensitivity in nonobese individuals.
Insulin resistance plays a major role in the pathophysiology of diabetes and is associated with obesity and cardiovascular disease. Excellent methods exist for the assessment of insulin sensitivity in the laboratory setting, such as the glucose clamp. However, these methods are not suitable for large population studies, and, thus, surrogate estimates of insulin sensitivity based on measurements in a single blood sample have been developed. Recently an index based on the logarithm and the reciprocal of the insulin-glucose product (QUICKI) has been proposed. QUICKI correlated with insulin sensitivity across the entire spectrum of glucose tolerance, but its performance was less satisfactory in normal subjects. Aim of this study was to ascertain whether the inclusion of fasting plasma free fatty acids concentration into QUICKI improves its association with insulin sensitivity in nonobese subjects. To test this hypothesis, we performed a euglycemic hyperinsulinemic clamp [40 mU/(m(2).min)] in 57 young, healthy, nonobese individuals with (n = 17) or without (n = 40) first-degree relatives affected by type 2 diabetes (the former group being an in vivo model of mild insulin resistance). We then compared the clamp-based index of insulin sensitivity with both QUICKI and a revised QUICKI, the latter index including the contribution of fasting free fatty acid concentration as well. The revised QUICKI considerably improved the relationship with the clamp-based index of insulin sensitivity (r = 0.51, P < 0.0001) with respect to QUICKI (r = 0.27, P < 0.05). In addition, the revised QUICKI revealed a reduction of insulin sensitivity in the offspring of type 2 diabetes (10%; P < 0.006) that QUICKI was unable to detect (3%; P = 0.28). In conclusion, this study suggests that the incorporation of fasting free fatty acid level into QUICKI is useful to improve its correlation with the clamp-based index of insulin sensitivity and its discriminatory power in case of mild insulin resistance. Further investigation is needed to ascertain its applicability to patients with obesity and type 2 diabetes.
Adult↗
Gender factors affect fatty acids-induced insulin resistance in nonobese humans: effects of oral steroidal contraception.
Plasma free fatty acids and intramyocellular triglycerides (IMCL) content modulate whole body insulin sensitivity in humans. To test whether the interactions between fatty acid metabolism and insulin action in nonobese humans are related to gender factors, we studied 15 young, normal weight, healthy men and 15 women matched for life habits and whole body insulin sensitivity, determined with the euglycemic-hyperinsulinemic clamp, by means of indirect calorimetry to assess substrate oxidation, localized (1)H nuclear magnetic resonance spectroscopy of calf muscles to assess IMCL content, and dual energy x-ray absorption to assess body composition. In addition, to test whether perturbation of the feminine hormonal milieu modifies these interactions, we studied 15 matched females using oral steroidal contraception (OSC). Insulin sensitivity in women, notwithstanding increased body fatness, plasma free fatty acids, IMCL content, and circulating beta-hydroxybutyrate levels and reduced lipid oxidation, was similar to that in men. Women using OSC showed a 40% reduction of insulin sensitivity associated with increased plasma free fatty acids, beta-hydroxybutyrate, cholesterol, and triglycerides levels and a slight increment in IMCL content compared with women with intact hormonal cycles. In all groups the IMCL content was inversely related to insulin sensitivity. In conclusion, nonobese, healthy, young women are as insulin sensitive as men, notwithstanding the higher levels of postabsorptive circulating and tissue-stored fatty acids; OSC-induced insulin resistance is associated with abnormal fatty acid metabolism and loss of this gender-related feature.
3-Hydroxybutyric Acid↗
Metabolic effects of restoring partial beta-cell function after islet allotransplantation in type 1 diabetic patients.
Successful intraportal islet transplantation normalizes glucose metabolism in diabetic humans. To date, full function is not routinely achieved after islet transplantation in humans, with most grafts being characterized by only partial function. Moreover, the duration of full function is variable and cannot be sufficiently predicted with available methods. In contrast, most grafts retain partial function for a long time. We hypothesized that partial function can restore normal protein and lipid metabolism in diabetic individuals. We studied 45 diabetic patients after islet transplantation. Labeled glucose and leucine were infused to assess whole-body glucose and protein turnover in 1) 6 type 1 diabetic patients with full function after intraportal islet transplantation (FF group; C-peptide > 0.6 nmol/l; daily insulin dosage 0.03 +/- 0.02 U x kg(-1) body wt x day(-1); fasting plasma glucose < 7.7 mmol/l; HbA1c < or = 6.5%), 2) 17 patients with partial function (PF group; C-peptide > 0.16 nmol/l; insulin dosage < 0.4 U x kg(-1) body wt x day(-1)), 3) 9 patients with no function (NF group; C-peptide < 0.16 nmol/l; insulin dosage > 0.4 U x kg(-1) body wt x day(-1)), and 4) 6 patients with chronic uveitis as control subjects (CU group). Hepatic albumin synthesis was assessed in an additional five PF and five healthy volunteers by means of a primed-continuous infusion of [3,3,3-2H3]leucine. The insulin requirement was 97% lower than pretransplant levels for the FF group and 57% lower than pretransplant levels for the PF group. In the basal state, the PF group had a plasma glucose concentration slightly higher than that of the FF (P = 0.249) and CU groups (P = 0.08), but was improved with respect to the NF group (P < 0.01). Plasma leucine (101.1 +/- 5.9 micromol/l) and branched-chain amino acids (337.6 +/- 16.6 micromol/l) were similar in the PF, FF, and CU groups, and significantly lower than in the NF group (P < 0.01). During insulin infusion, the metabolic clearance rate of glucose was defective in the NF group versus in the other groups (P < 0.01). Both the basal and insulin-stimulated proteolytic and proteosynthetic rates were comparable in the PF, FF, and CU groups, but significantly higher in the NF group (P = 0.05). In addition, the PF group had a normal hepatic albumin synthesis. Plasma free fatty acid concentrations in the PF and FF groups were similar to those of the CU group, but the NF group showed a reduced insulin-dependent suppression during the clamp. We concluded that the restoration of approximately 60% of endogenous insulin secretion is capable of normalizing the alterations of protein and lipid metabolism in type 1 diabetic kidney recipients, notwithstanding chronic immunosuppressive therapy. The results of the present study indicate that "success" of islet transplantation may be best defined by a number of metabolic criteria, not just glucose concentration/metabolism alone.
Adult↗