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O.13 In chronic renal failure (CRF) rats, impaired liver gluconeogenesis is associated with decreased phosphoenolpyruvate carboxykinase (PEPCK) activity
analysed again. Isotope plasma enrichments were measured by a gas chromatography mass spectrometry system. Turnover rates were calculated according to the formula of Steele as it applies to steady state conditions. Values are means _+SD. Results: 80min of adrenaline infusion resulted in comparable plasma adrenaline levels in N and CI (N: 8.0 _+ 1.6, CI: 10.9 _+ 4.1 nmol/I). Adrenaline in N significantly increased HGP from 14.3 _+ 1.3 to 21.5 + 1.9 #mol/kg/min, whereas HGP in CI remained unchanged (15.5 + 4.4 and 17.1 + 4.3 #mol/kg/min). GTO in N and CI was enhanced by adrenaline to a similar extent (N: from 2.6 + 0.9 to 6.2 _+ 1.7 ~mol/kg/min, CI from 2.6 +_ 0.7 to 5.2 + 2.5 pmol/kg/min). Conclusions: In contrast to the preserved stimulatory effect on peripheral lipolysis, adrenaline at supraphysiological plasma concentrations did not augment hepatic glucose production in patients with alcohol-induced liver cirrhosis. Since all patients had a rather advanced degree of liver disease this blunted stimulatory response to adrenaline could have been ascribed to a defect in hepatic gluconeogenesis - due to loss of functional cell mass - a depletion of hepatic glycogen stores or both.
O.13 In c h r o n i c renal failure (CRF) rats, impaired liver gluconeogenesis is associated with decreased phosphoenolpyruvate carboxykinase ( P E P C K ) activity N. C a n o *§, C. Chauvin §, C. Pizon §, R. Novaretti**, J. di Costanzo-Dufetel**, J. P. Reynier** and X. M. Leverve § *R#sidence du Parc-H6pital priv6, **Facult# de Pharmacie, Marseille and §Laboratoire de Th#rapeutique, Universit6 J. Fourier, Grenoble, France. Introduction: In hepatocytes isolated from CRF rats, gluconeogenesis was shown to be impaired [1]. Acidosis may be responsible for attered giuconeogenesis from amino acids but not from carbohydrates [2]. We tested the liver PEPCK activity, which is a possible site for decreased gluconeogenesis from carbohydrates, in CRF rats compared to sham-operated controls. In order to evaluate the effect of acidosis on PEPCK activity we also studied a group of CRF rats supplemented with NaHCO3 [CRFB]. Methods: CRF was obtained by a partial arterial ligation of the left kidney, followed after 2 weeks by a right nephrectomy. Metabolic studies were performed in fasting animals, 3 weeks after nephrectomy. CRF rats without [CRF] or with oral NaHCO3 [1.7% of food wt for 3 weeks,CRFB], presented with elevated serum creatinine [CRF 116 +_20, CRFB 90 _+7, sham-operated controls 51 + 2#M, m _+ sem] whereas body mass [CRF 341 _+ 9, CRFB 344 + 5, controls 374 _+ 14, g] and food intake [22 _+ 1.5g/d in each group] were similar in the 3 groups. Plasma bicarbonate was: CRF 19 _+ 1 mM, CRFB 23 _+ 1 mM, controls 24 + 1 mM. PEPCK activity (Vmax and Kin) was evaluated in presence of malate [0 to 15 mM] according to Chang and Lane [3] and the PEPCK mRNA by Northern Blotting (PCK 10 probe).
Results (m + sem, Student's t-test vs controls, *p < 0.05): Controlsn = 6 CRF n = 6 CRFBn = 6 PEPCKVm~, ~tmol/min/g wet weight PEPCKKin,mmol/I PEPCKmRNA% normal fasting values
3.06 -+0.30
2.10 + 0.57*
1.85 _+0.39*
0.4 100
0.4 100
0.4 100
Conclusion: CRF rats were characterized by a decrease in PEPCK activity, demonstrated by the Vmax decrease, which may account for the decrease in gluconeogenesis previously reported in the same model. The fasting levels of PEPCK mRNA were not altered by uremia, suggesting that the defect of PEPCK activity is located to the protein. The affinity constant of PEPCK was not
altered. Oral bicarbonate supplementation did not modify PEPCK activity in CRF animals.
References: [1] Kidney Int, May, 1995. [2] Clin Nutr 1994; 13 (suppl 1): 7. [3] J Biol Chem 1966; 244: 2413.
O.14 Renal function and urinary excretion of electrolytes in patients receiving long term parenteral cyclic nutrition ( L T P N ) M. Gerard-Boncompain *t, A. Hadj-Aissa**, N. Pozet**, F. M'Ghezzi* and D. Robert *t *Service de Reanimation M6dicale, HSpital de la Crix Rousse, Lyon, tCentre Agr6e de Nutrition Parent#rale de Lyon, **Explorations fonctionnelles r6nales, Pavilion P, H6pital Edouard Herriot, Lyon, France. Renal function has been rarely documented [1] in patients receiving LTPN, although this organ is of major importance for water, nitrogen, and electrolic balance. In 16 informed patients, 11 F, 5 M, aged 45.8 _+ 11, placed on LTPN for short bowel for 31 + 27 months, renal function was performed with gold standard techniques: inulin clearance as glomerular filtration rate (GFR) and PAH clearance as effective plasma flow (RPF). All patients received LTPN during the night from 9pm to 8am, including in one bag a mean volume of 2.7 _+ 0.71/D, mean caloric supply of 25.7 + 8.1 kcal/kg/D, as lipids 1.07 _+0.28 kcal/kg/D and dextrose 4.2 + 1.35 kcal/kg/D, nitrogen 0.20 + 0.04 g/kg/D, calcium 11.75 _+ 1.8 mMol/D, sodium 193 + 70 mMol/D, potassium 66.8 _+ 35 mMol/D, magnesium 17.37 + 4.8 mMol/D. To measure electrolyte excretion, urine was collected from 8am to 8pm (Day) before LTPN and from 8pm to 8am (night) during LTPN. GFR and RPF were measured after LTPN from 8am to 10am. Results: Urinary volume (V, ml) and excretion rates (mMol/12 h) of urea, sodium (Na), potassium (K), calcium (Ca), magnesium (Mg) were as follows: Day Night p
V
Urea
Na
I(
432_+230 82_+43 38_+34 21+10 1306-+642 166_+47 95-+54 28_+19 0.001 0.0001 0.0007 NS
Ca
Mg
1.5_+1.1 23+1.7 6~1+3.3 9.1 _+5.5 0.001 0.0011
GFR and RFP were normal in 7 patients (111 + 19 and 494 + 102 ml/min/1.73 m 2 respectively) and decreased in 9 patients (67 + 11 and 348 + 101 ml/min/1.73 m2). Conclusions: 1) About half of the patients with LTPN have decreased renal function which is not correlated with age and the duration of LTPN. 2) As expected, nocturnal infusion resulted in significant nocturnal urinary losses of electrolytes except for K. 3) In particular there is a nocturnal hypercalciuria which is not correlated with the amount of Ca infused.
Reference: [1] Buchman A.L. Serious renal impairment is associated with LTPN. JPEN 1993; 17(5): 438-444.
O.15 E i c o s a n o i d p r e c u r s o r s in diet and s e r u m potential factors in the p r o g r e s s i o n of diabetic nephropathy C. Holler 1, F. Ulberth 2, M. Auinger~ and K. Irsigler ~ 1L. Boltzmann Institute for Nutrition and 3rd Medical Department, Lainz, Vienna, Austria. 2Department of Dairy Research and Bakteriology, Agricultural Univ., Vienna, Austria. Numerous events in the pathogenesis of nephropathy are associated with an altered formation of eicosanoids. The aim of this
O.13 In c h r o n i c renal failure (CRF) rats, impaired liver gluconeogenesis is associated with decreased phosphoenolpyruvate carboxykinase ( P E P C K ) activity N. C a n o *§, C. Chauvin §, C. Pizon §, R. Novaretti**, J. di Costanzo-Dufetel**, J. P. Reynier** and X. M. Leverve § *R#sidence du Parc-H6pital priv6, **Facult# de Pharmacie, Marseille and §Laboratoire de Th#rapeutique, Universit6 J. Fourier, Grenoble, France. Introduction: In hepatocytes isolated from CRF rats, gluconeogenesis was shown to be impaired [1]. Acidosis may be responsible for attered giuconeogenesis from amino acids but not from carbohydrates [2]. We tested the liver PEPCK activity, which is a possible site for decreased gluconeogenesis from carbohydrates, in CRF rats compared to sham-operated controls. In order to evaluate the effect of acidosis on PEPCK activity we also studied a group of CRF rats supplemented with NaHCO3 [CRFB]. Methods: CRF was obtained by a partial arterial ligation of the left kidney, followed after 2 weeks by a right nephrectomy. Metabolic studies were performed in fasting animals, 3 weeks after nephrectomy. CRF rats without [CRF] or with oral NaHCO3 [1.7% of food wt for 3 weeks,CRFB], presented with elevated serum creatinine [CRF 116 +_20, CRFB 90 _+7, sham-operated controls 51 + 2#M, m _+ sem] whereas body mass [CRF 341 _+ 9, CRFB 344 + 5, controls 374 _+ 14, g] and food intake [22 _+ 1.5g/d in each group] were similar in the 3 groups. Plasma bicarbonate was: CRF 19 _+ 1 mM, CRFB 23 _+ 1 mM, controls 24 + 1 mM. PEPCK activity (Vmax and Kin) was evaluated in presence of malate [0 to 15 mM] according to Chang and Lane [3] and the PEPCK mRNA by Northern Blotting (PCK 10 probe).
Results (m + sem, Student's t-test vs controls, *p < 0.05): Controlsn = 6 CRF n = 6 CRFBn = 6 PEPCKVm~, ~tmol/min/g wet weight PEPCKKin,mmol/I PEPCKmRNA% normal fasting values
3.06 -+0.30
2.10 + 0.57*
1.85 _+0.39*
0.4 100
0.4 100
0.4 100
Conclusion: CRF rats were characterized by a decrease in PEPCK activity, demonstrated by the Vmax decrease, which may account for the decrease in gluconeogenesis previously reported in the same model. The fasting levels of PEPCK mRNA were not altered by uremia, suggesting that the defect of PEPCK activity is located to the protein. The affinity constant of PEPCK was not
altered. Oral bicarbonate supplementation did not modify PEPCK activity in CRF animals.
References: [1] Kidney Int, May, 1995. [2] Clin Nutr 1994; 13 (suppl 1): 7. [3] J Biol Chem 1966; 244: 2413.
O.14 Renal function and urinary excretion of electrolytes in patients receiving long term parenteral cyclic nutrition ( L T P N ) M. Gerard-Boncompain *t, A. Hadj-Aissa**, N. Pozet**, F. M'Ghezzi* and D. Robert *t *Service de Reanimation M6dicale, HSpital de la Crix Rousse, Lyon, tCentre Agr6e de Nutrition Parent#rale de Lyon, **Explorations fonctionnelles r6nales, Pavilion P, H6pital Edouard Herriot, Lyon, France. Renal function has been rarely documented [1] in patients receiving LTPN, although this organ is of major importance for water, nitrogen, and electrolic balance. In 16 informed patients, 11 F, 5 M, aged 45.8 _+ 11, placed on LTPN for short bowel for 31 + 27 months, renal function was performed with gold standard techniques: inulin clearance as glomerular filtration rate (GFR) and PAH clearance as effective plasma flow (RPF). All patients received LTPN during the night from 9pm to 8am, including in one bag a mean volume of 2.7 _+ 0.71/D, mean caloric supply of 25.7 + 8.1 kcal/kg/D, as lipids 1.07 _+0.28 kcal/kg/D and dextrose 4.2 + 1.35 kcal/kg/D, nitrogen 0.20 + 0.04 g/kg/D, calcium 11.75 _+ 1.8 mMol/D, sodium 193 + 70 mMol/D, potassium 66.8 _+ 35 mMol/D, magnesium 17.37 + 4.8 mMol/D. To measure electrolyte excretion, urine was collected from 8am to 8pm (Day) before LTPN and from 8pm to 8am (night) during LTPN. GFR and RPF were measured after LTPN from 8am to 10am. Results: Urinary volume (V, ml) and excretion rates (mMol/12 h) of urea, sodium (Na), potassium (K), calcium (Ca), magnesium (Mg) were as follows: Day Night p
V
Urea
Na
I(
432_+230 82_+43 38_+34 21+10 1306-+642 166_+47 95-+54 28_+19 0.001 0.0001 0.0007 NS
Ca
Mg
1.5_+1.1 23+1.7 6~1+3.3 9.1 _+5.5 0.001 0.0011
GFR and RFP were normal in 7 patients (111 + 19 and 494 + 102 ml/min/1.73 m 2 respectively) and decreased in 9 patients (67 + 11 and 348 + 101 ml/min/1.73 m2). Conclusions: 1) About half of the patients with LTPN have decreased renal function which is not correlated with age and the duration of LTPN. 2) As expected, nocturnal infusion resulted in significant nocturnal urinary losses of electrolytes except for K. 3) In particular there is a nocturnal hypercalciuria which is not correlated with the amount of Ca infused.
Reference: [1] Buchman A.L. Serious renal impairment is associated with LTPN. JPEN 1993; 17(5): 438-444.
O.15 E i c o s a n o i d p r e c u r s o r s in diet and s e r u m potential factors in the p r o g r e s s i o n of diabetic nephropathy C. Holler 1, F. Ulberth 2, M. Auinger~ and K. Irsigler ~ 1L. Boltzmann Institute for Nutrition and 3rd Medical Department, Lainz, Vienna, Austria. 2Department of Dairy Research and Bakteriology, Agricultural Univ., Vienna, Austria. Numerous events in the pathogenesis of nephropathy are associated with an altered formation of eicosanoids. The aim of this