Metabolic responses to intraduodenal glucose loading in insulin-infused diabetic dogs.
The hormonal and metabolic responses to an intraduodenal glucose load (0.5 g/kg) were first determined in eight normal dogs before diabetes (alloxan/streptozotocin) was induced and then comparison made of the responses to the glucose load when normal plasma glucose profiles were recreated by preprogrammed infusion of insulin via the portal or peripheral circulations. Basal intraportal and peripheral insulin infusions at 0.021 +/- 0.001 and 0.022 +/- 0.000 U . kg-1 . h-1, respectively, for 16 h to fasting diabetic dogs normalized peripheral plasma levels of glucose (5.5 +/- 0.3 and 5.6 +/- 0.6 mmol/liter, respectively), immunoreactive insulin (IRI) (11.5 +/- 1.2 and 16.4 +/- 1.6 microU/ml), glucagon (65 +/- 7 and 62 +/- 5 pg/ml), lactate (0.63 +/- 0.04 and 0.54 +/- 0.03 mmol/liter), and alanine (0.236 +/- 0.037 and 0.191 +/- 0.008 mmol/liter). However, peripheral but not intraportal infusion of insulin depressed levels of glycerol, nonesterified fatty acids (NEFA), and 3-hydroxybutyrate (0.074 +/- 0.006 vs. 0.109 +/- 0.013, P less than 0.01; 0.67 +/- 0.04 vs. 0.84 +/- 0.09, P less than 0.05; and 0.018 +/- 0.004 vs. 0.059 +/- 0.015 mmol/liter, P less than 0.01, respectively). With the preprogrammed insulin infusions used to normalize plasma glucose profiles to the intraduodenal glucose load, all hormonal and metabolic responses were normalized during intraportal infusion (IRI, 72.5 +/- 4.2 microU/ml; glucagon, 66 +/- 10 pg/ml; lactate, 1.06 +/- 0.10 mmol/liter; alanine, 0.251 +/- 0.042 mmol/liter; glycerol, 0.043 +/- 0.013 mmol/liter; NEFA, 0.24 +/- 0.03 mmol/liter; and 3-hydroxybutyrate, 0.012 +/- 0.007 mmol/liter) but marked hyperinsulinemia (103.2 +/- 6.1 microU/ml) and depressed glycerol, NEFA, and 3-hydroxybutyrate responses at 2 h (0.056 +/- 0.005, 0.52 +/- 0.10, and 0.019 +/- 0.010 mmol/liter, respectively) resulted during peripheral infusion. Therefore, only the portal route of insulin infusion achieved complete metabolic normalization during glucose loading in diabetic dogs.
D020155:3-Hydroxybutyric Acid; D000409:Alanine / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005990:Glycerol / Q000097:blood; D006885:Hydroxybutyrates / Q000097:blood; D007263:Infusions, Parenteral; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D007700:Kinetics; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008297:Male
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D006885:Hydroxybutyrates; D007328:Insulin; D007773:Lactates; D019344:Lactic Acid; D000409:Alanine; D005990:Glycerol; D020155:3-Hydroxybutyric Acid