β-Endorphin–Induced Inhibition and Stimulation of Insulin Secretion in Normal Humans Is Glucose Dependent Free

This study evaluated the effect of human β-endorphin on pancreatic hormone levels and their responses to nutrient challenges in normal subjects. Infusion of 0.5 mg/h β-endorphin caused a significant rise in plasma glucose concentrations preceded by a significant increase in peripheral glucagon levels. No changes occurred in the plasma concentrations of insulin and C-peptide. Acute insulin and C-peptide responses to intravenous pulses of different glucose amounts (0.33 g/kg and 5 g) and arginine (3 g) were significantly reduced by β-endorphin infusion (P < .01). This effect was associated with a significant reduction of the glucose disappearance rates, suggesting that the inhibition of insulin was of biological relevance. β-Endorphin also inhibited glucose suppression of glucagon levels and augmented the glucagon response to arginine. To verify whether the modification of prestimulus glucose level could be important in these hormonal responses to β-endorphin, basal plasma glucose concentrations were raised by a primed (0.5 g/kg) continuous (20 mg kg⁻¹ · min⁻¹) glucose infusion. After stabilization of plasma glucose levels (350 ± 34 mg/dl, f = 120 min), β-endorphin infusion caused an immediate and marked increase in plasma insulin level (peak response 61 ± 9 μU/ml, P < .01), which remained elevated even after the discontinuation of opioid infusion. Moreover, the acute insulin response to a glucose pulse (0.33 g/kg i.v.) given during β-endorphin infusion during hyperglycemia was significantly higher than the response obtained during euglycemia (171 ± 32 vs. 41 ± 7 μU/ml, P < .01). Therefore, during euglycemia, β-endorphin infused at low pharmacological dose in normal humans inhibits basal and nutrient-stimulated insulin secretion, raises plasma glucose and glucagon concentrations, and increases the glucagon response to arginine. Also, during hyperglycemia (glucose clamp), β-endorphin stimulates basal and glucose-induced insulin secretion. Hyperglycemia alters the reactivity of the β-cells to β-endorphin.