Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have shown that hypoglycemia may reduce counterregulatory responses to subsequent hypoglycemia in healthy subjects and in patients with diabetes. The effect of hypoglycemia on the hormonal response to a nonhypoglycemic stimulus is uncertain. To test the hypothesis that the cortisol response to corticotropin (ACTH) infusion is independent of antecedent hypoglycemia, 10 healthy subjects received a standard ACTH infusion (0.25 mg Cosyntropin [Organon, West Orange, NJ] intravenously over 240 minutes) at 8:00 AM on day 1 and day 3 and a hypoglycemic insulin clamp study (1 mU/kg/min) at 8:00 AM on day 2. During the hypoglycemic clamp, plasma glucose decreased from 5.0 mmol/L to 2.8 mmol/L for two periods of 120 minutes (mean glucose, 2.9 +/- 0.03 and 2.8 +/- 0.02 mmol/L, respectively) separated by a 60-minute interval of euglycemia (mean glucose, 4.7 +/- 0.01 mmol/L). Seven subjects also had paired control studies in random order during which a 330-minute euglycemic clamp (mean glucose, 5.0 +/- 0.11 mmol/L) instead of a hypoglycemic clamp was performed on day 2. Basal ACTH (4.6 +/- 0.7 v 2.6 +/- 0.4 pmol/L, P < .02) and basal cortisol (435 +/- 46 v 317 +/- 40 nmol/L, P < .02) both decreased from day 1 to day 3 following intervening hypoglycemia. In contrast, with intervening euglycemia, neither basal ACTH (5.9 +/- 1.5 v 4.5 +/- 1.0 pmol/L) nor basal cortisol (340 +/- 38 v 318 +/- 60 nmol/L) were reduced significantly on day 3 compared with day 1. Following interval hypoglycemia, the area under the curve (AUC) for the cortisol response to successive ACTH infusions was increased (4,734 +/- 428 nmol/L over 240 minutes [day 3] v 3,526 +/- 434 nmol/L over 240 minutes [day 1], P < .01). The maximum incremental cortisol response was also significantly increased (805 +/- 63 nmol/L (day 3) v 583 +/- 58 nmol/L (day 1), P < .05). In contrast, the AUC for the cortisol response to successive ACTH infusions with interval euglycemia (3,402 +/- 345 nmol/L over 240 minutes [day 3] v 3,709 +/- 391 nmol/L over 240 minutes [day 1] and the incremental cortisol response (702 +/- 62 nmol/L [day 3] v 592 +/- 85 nmol/L [day 1] were unchanged. Following exposure to intermittent hypoglycemia in healthy humans, fasting morning ACTH and cortisol levels are reduced and the incremental cortisol response to an infusion of ACTH is enhanced. The enhanced cortisol response to exogenous ACTH infusion after intervening hypoglycemia (but not intervening euglycemia) may reflect priming of the adrenal gland by endogenous ACTH produced during the hypoglycemia. These data suggest that adrenal function testing by exogenous ACTH administration is not impaired by prior exposure to hypoglycemia. Moreover, the reduced cortisol response to recurrent hypoglycemia in patients with well-controlled diabetes is not likely the result of impaired adrenal responsiveness.
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PMID:Recurrent hypoglycemia does not impair the cortisol response to adrenocorticotropin infusion in healthy humans. 978 30

This review in honor of David de Wied summarizes the work done in my laboratory that first indicated that adrenocorticotropic hormone (ACTH) has a direct effect on the neuromuscular system. Cold stress or ACTH and its related peptides alpha-melanocyte-stimulating hormone (alpha-MSH ) and beta-lipotropin improve the electromechanical characteristics of adrenalectomized and hypophysectomized rats. ACTH-(1-39) accelerates the return of motor and sensory function and improves the morphological characteristics of the motor endplate after peripheral nerve crush. The non-corticotropic fragments ACTH-(4-10), alpha-MSH, the ACTH-(4-9) analogue Organon 2766 (Org 2766) or the ACTH-(4-10) analogue Biomeasure 22015 (BIM 22015) improve electrophysiological and morphological parameters of the regenerating neuromuscular system. ACTH-(4-10) immunoreactivity, present in ventral horn motor neurons in low levels, is decreased ipsilaterally following ipsilateral nerve crush but increases both ipsilaterally and contralaterally if injured animals are treated with ACTH-(4-10) indicating a neuroprotective action. Similarly, Org 2766 appears to have a protective action in the brain following nigrostriatal lesions. In developmental studies, perinatal exposure to ACTH peptides improves the structure of the neuromuscular junction, accelerates the maturation of electromechanical properties and enhances nerve-muscle integration and nerve regeneration. Perinatal exposure to these peptides decreases adult male sexual behavior, a change correlated with increased serotinergic input within the medial preoptic area. Similar changes occur in female rats and appear to be long-lasting. In tissue culture studies, both Org 2766 and BIM 22015 promote neurite outgrowth in the absence of nerve growth factor, indicating a neurotrophic role for these peptides.
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PMID:David and Goliath - the slingshot that started the neuropeptide revolution. 1103 9