Although it is well established in several mammalian species that ,3-adrenoceptors play a major role in regulating lipolysis and thermogenesis in adipose tissue, the functional existence and role of this receptor subtype in man has been controversial. We investigated whether the .33-adrenoceptor functionally co-exists with Clin. Invest. 1995. 95:2239-2245

This study was undertaken to examine whether insulin resistance in adolescents with poorly controlled type 1 diabetes mellitus (T1DM) is associated with the failure of insulin to suppress lipolysis in adipose and muscle tissues. Using microdialysis techniques, extracellular fluid concentrations of glycerol was measured in adipose and muscle tissue 3 h before and 3 h during a 0.8 mU · kg Ϫ1 · min Ϫ1 · euglycemic clamp. Ten adolescents with poorly controlled T1DM (HbA 1c 10.2 Ϯ 0.2%) were compared with six healthy lean adolescent control subjects. Despite similar increases in plasma insulin in both groups, diabetic subjects exhibited a 39% reduction in peripheral glucose uptake compared with controls (p Ͻ 0.05). In contrast, hepatic glucose production was fully suppressed by insulin in diabetic subjects. At the end of the clamp, extracellular glycerol concentrations were significantly elevated in subjects with diabetes (muscle: 85 Ϯ 7 M for diabetics and 51 Ϯ 8 M for controls, p Ͻ 0.01; adipose: 149 Ϯ 23 M for T1DM and 82 Ϯ 11 M for controls, p Ͻ 0.05), indicating impaired in situ suppression of lipolysis in patients with diabetes. With all subjects considered, the rate of insulin-stimulated metabolism was inversely correlated to glycerol concentration in both adipose (r ϭ Ϫ0.63, p Ͻ 0.01) and muscle (r ϭ Ϫ0.63, p Ͻ 0.01). Our data suggest that failure of insulin to inhibit lipolysis in muscle and adipose tissue contributes to the severe peripheral insulin resistance that characterizes poorly controlled T1DM during adolescence. Type 1 diabetes mellitus (T1DM) in adolescents is a disease in which end organ resistance to insulin and deficiency of the hormone coexist (1). During normal puberty, responsiveness to insulin declines and this physiologic insulin resistance is exaggerated by poorly controlled diabetes (1-3). Compared with healthy lean preadolescents, healthy lean adolescents show a selective defect in insulin's ability to stimulate nonoxidative glucose disposal in peripheral (muscle and adipose) tissues; insulin-mediated increases in peripheral glucose oxidation are unaffected by normal puberty (4, 5). In contrast, the exaggerated insulin resistance in adolescents with poorly controlled T1DM involves defects in insulin's ability to stimulate both oxidative and nonoxidative glucose metabolism (5).An implication of the much debated glucose fatty-acid cycle (Randle cycle) is that increased FFA availability interferes with muscle glucose metabolism and contributes to the cause of many insulin-resistant states, including adolescence and T1DM (6 -8). Using the insulin clamp technique and indirect calorimetry, we have shown that severely insulin-resistant adolescents with poorly controlled T1DM fail to suppress circulating FFA levels or rates of fat oxidation in comparison with healthy adolescent controls in response to insulin levels similar to those achieved postprandially by healthy adolescents (5). The wholebody methods used in that study, however, did not allow us to distinguish the relative contributions of...