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 i f glycemia is well controlled and may be to normal by means of prehepa tic insulin substitution, Therefore, the present study was designed 1) to investigate the influence of route of insulin administration (port al versus peripheral) on the urea production rate, which is considered to measure amino acid catabolism, and 1) to elucidate the impact of d ifferent food-protein intake. Paired studies were conducted in chronic insulin-dependent diabetic dogs maintained normoglycemic. Diabetic an imals and nondiabetic controls were fed either a high-protein diet (46 % of energy intake provided by proteins; study 1) or a low-protein car bohydrate-supplemented diet (20% of energy intake provided by protein; study 2) for 2 days, and nux rates of glucose and urea were measured using isotope dilution techniques. In both studies, the diabetic anima ls were maintained normoglycemic by glucose-controlled insulin infusio n delivered either systemically or portally. In study 1 versus study 2 , the animals showed lower alpha-amino nitrogen levels and concentrati ons of gluconeogenic amino acids, predominantly alanine. There were no significant differences in plasma glucose and glucose turnover betwee n the experimental groups on either systemic or portal insulin infusio n versus controls; however, peripheral insulin levels were higher for diabetic animals maintained with systemic versus portal insulin delive ry (P < 0.05). No significant differences in glucagon, lactate, pyruva te, nonesterified fatty acids, or beta-hydroxybutyrate were observed, Urea production was significantly higher in study 1 compared with stud y 2: 7.48 +/- 0.83 vs. 5.97 +/- 0.59 mu mol . kg(-1) . min(-1) (normal dogs); 12.97 +/- 1.86 vs. 5.54 +/- 0.60 mu mol . kg(-1) . min(-1) (di abetic dogs on portal insulin); 16.11 +/- 2.59 vs. 6.82 +/- 0.70 mu mo l . kg(-1) . min(-1) (diabetic dogs on systemic insulin infusion); P < 0.05 for all. The diabetic dogs maintained normoglycemic with systemi c insulin infusions had significantly higher rates of urea synthesis t han those with portal insulin infusion (P < 0.05). It is concluded tha t in IDDM, even if normoglycemia is managed, there is significantly in creased amino acid catabolism with posthepatic systemic insulin treatm ent. This increased catabolic rate is more pronounced during high-prot ein nourishment.