Effects of an acute increase in epinephrine and cortisol on carbohydrate metabolism during insulin deficiency.

Goldstein RE, Abumrad NN, Lacy DB, Wasserman DH, Cherrington AD
Diabetes. 1995 44 (6): 672-81

PMID: 7789632 · DOI:10.2337/diab.44.6.672

This study was undertaken to investigate the effects of an acute increase in the plasma epinephrine level, with or without an accompanying increase in the plasma cortisol level, during selective insulin deficiency on glycogenolysis and gluconeogenesis in conscious overnight-fasted dogs. Experiments consisted of an 80-min tracer and dye equilibration period, a 40-min basal period, and a 180-min experimental period. In all protocols, selective insulin deficiency was created during the experimental period by infusing somatostatin peripherally (0.8 micrograms.kg-1.min-1) with basal replacement of glucagon intraportally (0.65 ng.kg-1.min-1). In EPI+SAL (n = 6), an additional infusion of epinephrine (0.04 micrograms.kg-1.min-1) was infused during the experimental period along with saline. In EPI+CORT (n = 6), hydrocortisone (3.0 microgram.kg-1.min-1) was infused in addition to epinephrine during the experimental period. In SAL+CORT (n = 5), hydrocortisone was infused during the experimental period. In SALINE (n = 5), neither epinephrine nor cortisol was infused. [3-3H]glucose, [U-14C]alanine, and indocyanine green dye were used to assess glucose production (rate of appearance [Ra]) and gluconeogenesis using tracer and arteriovenous difference techniques. During selective insulin deficiency in SALINE, the arterial plasma glucose level increased from 6.0 +/- 0.1 to 15.8 +/- 1.1 mmol/l; Ra increased from 14.7 +/- 0.7 to 24.9 +/- 1.7 mumol.kg-1.min-1. Gluconeogenic efficiency and the conversion of alanine and lactate to glucose increased to 300 +/- 55 and 355 +/- 67% of basal. In EPI+SAL and EPI+CORT, plasma glucose increased from 6.2 +/- 0.1 to 19.8 +/- 0.9 mmol/l and from 6.3 +/- 0.1 to 19.5 +/- 0.9 mmol/l. In EPI+SAL and EPI+CORT, Ra increased from 16.5 +/- 1.1 to 29.3 +/- 3.2 mumol.kg-1.min-1 and from 15.4 +/- 1.3 to 28.3 +/- 2.5 mumol.kg-1.min-1. The rise in gluconeogenic efficiency was similar to the rise that occurred in SALINE, but gluconeogenic conversion increased 17-fold in each of the two epinephrine groups. During the epinephrine infusion, gluconeogenesis accounted for a maximum of 55% of total glucose production as opposed to 31% during insulin deficiency alone. An increase in cortisol alone during insulin deficiency (SAL+CORT) had no effect on glucose level, glucose production, or gluconeogenesis. These results suggest that small increases in the plasma epinephrine level during insulin deficiency can significantly worsen the resulting hyperglycemia through stimulation of both glycogenolysis and gluconeogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)

MeSH Terms (15)

Alanine Animals Blood Glucose Carbohydrate Metabolism Dogs Epinephrine Glucagon Gluconeogenesis Glycerol Glycogen Hydrocortisone Insulin Lactates Liver Norepinephrine

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