Increased urea synthesis in insulin-dependent diabetic dogs maintained normoglycemic: effect of portal insulin administration and food protein content.

In IDDM, the gluconeogenic turnover of amino acids is increased even if glycemia is well controlled and may be restored to normal by means of prehepatic insulin substitution. Therefore, the present study was designed 1) to investigate the influence of route of insulin administration (portal versus peripheral) on the urea production rate, which is considered to measure amino acid catabolism, and 2) to elucidate the impact of different food-protein intake. Paired studies were conducted in chronic insulin-dependent diabetic dogs maintained normoglycemic. Diabetic animals and nondiabetic controls were fed either a high-protein diet (46% of energy intake provided by proteins; study 1) or a low-protein carbohydrate-supplemented diet (20% of energy intake provided by protein; study 2) for 2 days, and flux rates of glucose and urea were measured using isotope dilution techniques. In both studies, the diabetic animals were maintained normoglycemic by glucose-controlled insulin infusion delivered either systemically or portally. In study 1 versus study 2, the animals showed lower alpha-amino nitrogen levels and concentrations of gluconeogenic amino acids, predominantly alanine. There were no significant differences in plasma glucose and glucose turnover between the experimental groups on either systemic or portal insulin infusion versus controls; however, peripheral insulin levels were higher for diabetic animals maintained with systemic versus portal insulin delivery (P < 0.05). No significant differences in glucagon, lactate, pyruvate, nonesterified fatty acids, or beta-hydroxybutyrate were observed. Urea production was significantly higher in study 1 compared with study 2: 7.48 +/- 0.83 vs. 5.97 +/- 0.59 micromol / kg / min (normal dogs); 12.97 +/- 1.86 vs. 5.54 +/- 0.60 micromol / kg / min (diabetic dogs on portal insulin); 16.11 +/- 2.59 vs. 6.82 +/- 0.70 micromol / kg / min (diabetic dogs on systemic insulin infusion); P < 0.05 for all. The diabetic dogs maintained normoglycemic with systemic insulin infusions had significantly higher rates of urea synthesis than those with portal insulin infusion (P < 0.05). It is concluded that in IDDM, even if normoglycemia is managed, there is significantly increased amino acid catabolism with posthepatic systemic insulin treatment. This increased catabolic rate is more pronounced during high-protein nourishment.

Novel urinary metabolite of alpha-tocopherol, 2,5,7,8-tetramethyl-2(2'-carboxyethyl)-6-hydroxychroman, as an indicator of an adequate vitamin E supply?

Previously, the metabolism of alpha-tocopherol was considered to involve the opening of the chroman structure because of its oxidation to tocopherylquinone. In contrast, we describe here 2,5,7,8-tetramethyl-2(2'-carboxyethyl)-6-hydroxychroman (alpha-CEHC) as the major urinary metabolite of alpha-tocopherol that appears in human urine after vitamin E supplementation. It is formed directly from alpha-tocopherol without previous oxidative splitting of the chroman ring. The correlation of alpha-tocopherol intake, plasma alpha-tocopherol concentrations, and urinary excretion of alpha-CEHC in human volunteers supplemented with RRR-alpha-tocopherol dosages ranging from 0 to 800 mg/d was examined. HPLC and gas chromatography-mass spectroscopy analysis revealed that alpha-CEHC was only excreted when a plasma threshold of 7-9 mumol alpha-tocopherol/g total lipid was exceeded. This concentration was obtained by a daily intake of approximately 50-150 mg alpha-tocopherol. We suggest that alpha-CEHC excretion indicates a saturated binding capacity of vitamin E in the plasma and thus may be considered to be a marker of optimum vitamin E intake.

[Mass spectrometric structure analysis of fatty acid mixtures from biological material after gas capillary chromatographical separation]. / Massenspektrometrische Strukturanalyse von Fettsäuregemischen aus biologischem Material nach kapillargaschromatographischer Trennung.

The identification of mixtures of fatty acids from biological materials is possible by electron impact ionization mass spectra of methyl esters after their capillary gas chromatographic separation. Mass spectra of pyrrolidine derivatives are used for the determination of double bond positions in unsaturated fatty acids. 97 different fatty acids (saturated, unsaturated, branched, cyclic, hydroxy, oxo, epoxy and methoxy) and other compounds (alkanes, halogens, phthalates, ketones, aldehydes) were identified in yeast and bacterial biomasses, lipid-containing animal tissues and human sera as well as fish and plant oils (77 preparations).

Metabolism of alpha-hexachlorocyclohexane. Free metabolites in urine and organs of rats.

k1. The alpha-isomer of 1,2,3,4,5,6-hexachlorocyclohexane (HCH) is converted in rats to 1,2,4-trichlorobenzene, 2,3,4-trichlorophenol, 2,4,6-trichlorophenol, other trichlorophenols, and 2,3,4,6-tetrachlorophenol, which were excreted in urine. 2. Alpha-HCH is also converted to 3,4,6/5-pentachlorocyclohexene which is detectable in kidneys, but not in urine. 3. The results of this study are discussed with references to earlier work and to gamma-HCH metabolism.