The metabolic and hormonal adaptations of normal dogs to long-term exogenous sulfated insulin infusions.
Hyperinsulinism frequently accompanies glucose normalization in type I diabetes but the long-term consequences of this exaggerated hormonal state are not known. To study this condition, normal dogs received constant exogenous sulfated insulin infusions for prolonged periods up to 43 weeks. During the interval and inspite of prevailing postabsorptive and fasting hypoglycemia, overt resistance to the infused insulin or loss of sensitivity did not occur. In counterring the imposed fasting hyperinsulinemia and the resulting hypoglycemia, fasting pancreatic glucagon levels rose while the fasting levels of several glucogenic precursors (lactate, pyruvate, and alanine) decreased. Fasting free fatty acid (FFA) levels were suppressed, but beta-hydroxybutyrate (beta-OHB) levels were unchanged. Body weight did not change. Most remarkably, all changes measured in the fasting levels of the hormones and metabolites reverted to normal following the cessation of exogenous sulfated insulin infusion. In addition to the hormonal and metabolite adaptations invoked by chronic exogenous hyperinsulinism in the fasting state of these normal dogs, there were interesting responses to their usual mixed meals. Of particular interest in this regard were the plasma glucose, insulin, and FFA diurnal profiles. First of all, a definite and unusual postprandial glycemic excursion occurred. Second, insulin levels were elevated some sixfold, and rather unresponsive to the meal in general. Inspite of the depressed fasting FFA levels and the absence of a postprandial rise in insulinemia, FFA showed a distinct fall after the meal. Whether the sulfated insulins infused were of the bovine or porcine species of origin made no discernible difference.(ABSTRACT TRUNCATED AT 250 WORDS)
D020155:3-Hydroxybutyric Acid; D000222:Adaptation, Physiological; D000409:Alanine / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002940:Circadian Rhythm; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D005755:Gastrins / Q000097:blood; D005934:Glucagon / Q000097:blood*; D006885:Hydroxybutyrates / Q000032:analysis; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008297:Male; D011773:Pyruvates / Q000097:blood; D019289:Pyruvic Acid; D013431:Sulfates; D013997:Time Factors
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D005755:Gastrins; D006885:Hydroxybutyrates; D007328:Insulin; D007773:Lactates; D011773:Pyruvates; D013431:Sulfates; D019344:Lactic Acid; D005749:Gastric Inhibitory Polypeptide; D019289:Pyruvic Acid; D005934:Glucagon; D000409:Alanine; D020155:3-Hydroxybutyric Acid