The role of the central nervous system in modulating glucose and protein metabolism during insulin-induced hypoglycemia

Abstract

We previously established that insulin-induced hypoglycemia is associated with enhanced proteolysis with the GI tract being the major contributor to this response. In the present study we examined whether brain hypoglycemia modulates the changes in amino acid and glucose kinetics during insulin-induced hypoglycemia. Studies were performed in 24 h faster conscious dogs chronically fitted with catheters in the femoral artery, portal vein, hepatic vein, femoral vein and in both carotid and vertebral arteries, and that were also fitted with permanent tracheostomies. Following a 30 min basal period insulin was infused i.v. at 300 mU/kg·h to achieve systemic hypoglycemia averaging 42±2mg/dl. In group 1 ( n = 6) both central and systemic (global) hypoglycemia was allowed to develop. The rate of net hepatic glucose output (NHGO) increased by 50% above basal. Plasma leucine increased from 120 ± 12 μmol/1 basally to 154 ± 30 μmol/1 during the last hour of hypoglycemia. The rate of leucine appearance into the plasma compartment ( R u) increased from 154 ± 30 to 200 ± 36 μmol/kg·h and its rate of oxidation increased from 22 ± 5 to 51 ± 8 μmol/kg·h, while its non-oxidative rate of disposal (141 ± 12 μmol/kg·h) did not change. Net leucine balance across the gut was neutral (6 ± 5 μmol/kg·h) and switched to net output of 96 ± 24 μmol/kg·h. In group II ( n = 5) 10% dextrose in water was infused into both carotid and vertebral arteries to prevent profound CNS glucopenia. This was associated with a drop in NHGO. Plasma leucine dropped from 143 ± 9 to 39 ± 7 μmol/I, leucine R u dropped from 165 ± 15 to 60 ± 9 μmol/kg·h, leucine oxidation dropped from 34 ± 9 to 9 ± 2 μmol/kg·h and non-oxidative R u dropped from 129 ± 15 to 54 ± 6 μmol/kg·h (all P < 0.001); net leucine balance across the gut was neutral and did not change (5 ± 6 to 16 ± 7 μmol/kg·h). We conclude that the proteolytic response of insulin-induced hypoglycemia, and particularly that of the gl tract can be totally attributed to CNS glucopenia. Systemic glucopenia plays a very minor role in this response.