title: Extrapancreatic effects of L-leucine infusion in leucine-sensitive and control subjects.
abstract: We studied the extrapancreatic effects of L-leucine infusion (2.5 mumol/kg/min) in six controls (three females, three males) and three members of a family with leucine-sensitive hypoglycemia (LSH). Total glucose disposal and endogenous glucose production (EGP) rates were assessed after an overnight fast (12 to 14 hour) during somatostatin (SRIF) infusion (500 micrograms/h) with insulin replacement (0.2 mU/kg/min), combined with D-(3-3H)-glucose infusion. Additional studies of forearm arterial-venous (A-V) balances of amino acids, glucose, and other substrates, combined with L-(1-14C)-leucine kinetics, were done in these two groups. L-leucine infusion resulted in a 15% decrease in whole-body total glucose utilization in controls (P less than .05) during SRIF-insulin infusion, but did not affect glucose utilization in LSH subjects. EGP was not affected by L-leucine infusion in either group. Control subjects demonstrated a significant reduction in forearm glucose uptake and greater lactate release during L-leucine infusion, compared to the basal state. In contrast, subjects with LSH showed a slight increase in forearm glucose uptake and significantly less lactate release during L-leucine infusion. Subjects with LSH demonstrated significantly lower forearm leucine uptake, and lower rates of appearance and oxidation of L-(1-14C)-leucine during leucine infusion, compared to controls. Our data suggest that members of this LSH kindred have a defect in intracellular leucine metabolism in skeletal muscle, resulting in a lack of leucine-induced inhibition of glucose utilization. This may contribution to the development of hypoglycemia in these subjects.
mesh_terms: D000293:Adolescent; D000328:Adult; D005215:Fasting; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000378:metabolism*; D007328:Insulin; D007700:Kinetics; D007930:Leucine / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism; D013004:Somatostatin
chemical_list: D007328:Insulin; D013004:Somatostatin; D007930:Leucine; D005947:Glucose