Role of glucagon in enhancing ketone body production in ketotic diabetic man.
To assess the role of endogenous glucagon in regulating hepatic ketone body production in ketotic insulin-withdrawn diabetic subjects, ketone body kinetics were determined in two groups of C-peptide-negative diabetics 6 h after interruption of a s.c. insulin infusion. In group 1 (N = 5), glucagon levels were suppressed by infusion of somatostatin (SRIF), whereas in group 2 (N = 6) glucagon was replaced during SRIF by infusing glucagon at 2 ng/kg/min. Ketone body production rates as determined by primed-continuous infusion of [3-14C]acetoacetate declined from 19.5 +/- 0.8 to 16.4 +/- 0.4 mumol/kg/min (P less than 0.01) during 105 min of SRIF-induced glucagon suppression, whereas they remained unchanged (+0.2 +/- 0.4 mumol/kg/min, P less than 0.01 compared with SRIF) during glucagon replacement. Total ketone body concentrations remained unchanged during SRIF infusion but increased from 2.2 +/- 0.3 to 2.9 +/- 0.2 mmol/L (P less than 0.01) during glucagon replacement. The metabolic clearance rate of total ketone bodies declined significantly (P less than 0.01) by 27% and 21% in the two groups. Plasma free fatty acid and glycerol concentrations remained unchanged in both groups whereas plasma glucose decreased by 3.2 +/- 0.5 mmol/L during SRIF (P less than 0.01). Thus, endogenous glucagon contributed significantly to the maintenance of ketone body production rates in ketotic insulin-deficient diabetics. Since ketogenesis was altered in the absence of changes in free fatty acid levels, the results suggested that glucagon enhanced ketogenesis by an intrahepatic effect.
D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D016883:Diabetic Ketoacidosis / Q000378:metabolism / Q000503:physiopathology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000494:pharmacology / Q000502:physiology*; D005990:Glycerol / Q000097:blood; D006801:Humans; D007328:Insulin / Q000502:physiology; D007657:Ketone Bodies / Q000096:biosynthesis* / Q000097:blood; D008297:Male; D008875:Middle Aged; D013004:Somatostatin / Q000494:pharmacology
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007657:Ketone Bodies; D013004:Somatostatin; D005934:Glucagon; D005990:Glycerol