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Altered Metabolic and Hormonal Responses to Epinephrine and β-Endorphin in Human Obesity

Istituto di Medicina Generale, Terapia Medica e Malattie del Metabolismo, First Facolta di Medicina, Universita di Napoli (D.G., D.C., T.S., R.T., F.D.) Naples Italy
The Radioimmunassay Laboratory (P.F.) and the Division of Diabetes, Institute of Medicine (P.J.L.), University of Liege Liege, Belgium

Address requests for reprints to: Dario Giugliano, M.D., Cattedra di Diabetologia e Dietoterapia, 1° Policlinico Universitario, Piazza L. Miraglia, 80138 Naples, Italy.

Catecholamines and endogenous opioid peptides are released in response to stress. Exogenous infusions of epinephrine and β-endorphin (both in doses of 15, 50, and 80 ng/ kg-min sequentially, each dose lasting 30 min) were used to mimic short term stress in both normal weight (body mass index, <25 kg/m²) and obese (body mass index, >30 kg/m²) subjects. Fasting plasma insulin, C-peptide, and β-endorphin concentrations were significantly higher in the obese than in the normal subjects (P < 0.01–0.005).

In lean subjects epinephrine produced significant increases in plasma glucose levels, but no appreciable changes in plasma insulin, C-peptide, or glucagon. Infusion of β-endorphin in the same subjects caused plasma glucose and glucagon to rise, but insulin and C-peptide levels did not change. The simultaneous infusion of epinephrine and β-endorphin produced a glycemic response which, although greater, was not significantly different than the sum of the responses to the individual hormone infusions. However, the two hormones had a synergistic interaction on plasma glucagon levels [total glucagon response, 2275 ± 370 pg/min-mL (ng/min-L); sum of single effects, 750 ± 152 (±SE) pg/min-mL (ng/min-L); P < 0.01]. The plasma epinephrine [207 ± 21, 607 ± 70, and 1205 ± 134 pg/mL (1130 ± 115, 3640 ± 382, and 6577 ± 691 pmol/L] and β-endorphin [875 ± 88,1250 ± 137, and 1562 ± 165 pg/mL (250 ± 25, 358 ± 39, and 447 ± 47 pmol/L] concentrations attained during the infusions of each single hormone were not different from those recorded during the combined hormonal infusion.

In obese subjects epinephrine raised plasma glucose levels and caused dose-related increments of plasma glucagon concentrations. Plasma insulin and C-peptide concentrations remained low and rebounded at the end of the infusions. In the same subjects, β-endorphin produced elevations of plasma glucose, insulin, C-peptide, and glucagon. When the combined hormonal infusion was given to obese subjects, the plasma epinephrine and β-endorphin concentrations rose to values not significantly different from those in normal weight subjects. However, there was a dramatic increase in plasma glucose exceeding 200 mg/dL (11.1 mmol/L), which remained elevated 30 min after the infusion. The glucagon response was not greater than the sum of the single effects.

Thus, 1) in normal weight people, a synergistic interaction between epinephrine and β-endorphin contributes to the elevated plasma glucagon concentrations and might be important in the mediation of stress-induced glucagon release; and 2) in obese people, a synergistic interaction between epinephrine and 3-endorphin produces a marked and sustained elevation of plasma glucose levels.

Received November 23, 1987.

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