Effects of insulin on whole body and forearm leucine and KIC metabolism in type 1 diabetes

Abstract

To investigate whole body rates of appearance (Ra) and forearm metabolism of leucine and alpha-ketoisocaproate (KIC) in type 1 diabetes, before and after insulin administration, seven diabetic subjects were studied in the postabsorptive state with primed-constant infusions of L-[4,5-3H]leucine and [1-14C]KIC, and forearm arterial deep-venous catheterization. This combined technique allowed the selective quantitation of the two processes regulating forearm leucine and KIC metabolism (release and uptake) that may occur simultaneously. Before insulin (arterial plasma glucose, 284 +/- 24 mg/dl; leucine, 215 +/- 24 mumol/l; KIC, 42 +/- 3 mumol/l) forearm leucine and KIC release exceeded uptake slightly but significantly (P less than 0.05). During a 180-min insulin infusion, arterial glucose (144 +/- 27 mg/dl) and leucine concentrations (130 +/- 15 mumol/l) decreased (P less than 0.05 or less vs. base line) toward normal, whereas KIC did not change (33 +/- 4 mumol/l, NS). However, no net uptake of either leucine or KIC across the forearm was detected at any time point. In contrast, a significant net release of these substrates occurred throughout the insulin infusion. By the end of the hormone administration, whole body leucine and KIC Ra decreased 17 and 33%, respectively (P less than 0.01). However, forearm uptake and release of leucine and KIC did not significantly change with respect to base line. The fraction of whole body leucine released from estimated total muscle mass did not change (54 to 48%, NS) before vs. after insulin.(ABSTRACT TRUNCATED AT 250 WORDS)