Opioid Receptor Activation Impairs Hypoglycemic Counterregulation in Humans
| العنوان: | Opioid Receptor Activation Impairs Hypoglycemic Counterregulation in Humans |
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| المؤلفون: | Armand Mbanya, Ilan Gabriely, Meredith Hawkins, Nora Tomuta, Akankasha Goyal, Eric Lontchi-Yimagou, Harry Shamoon, Michelle Carey, Oana A. Sandu, Rebekah Gospin, Raphael Hulkower |
| المصدر: | Diabetes |
| بيانات النشر: | American Diabetes Association, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Adult, Blood Glucose, Male, medicine.medical_specialty, Epinephrine, Hydrocortisone, medicine.drug_class, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030209 endocrinology & metabolism, Hypoglycemia, 03 medical and health sciences, Norepinephrine, 0302 clinical medicine, Opioid receptor, Internal medicine, Diabetes mellitus, Internal Medicine, Medicine, Humans, Insulin, Glycemic, Type 1 diabetes, Cross-Over Studies, C-Peptide, Morphine, business.industry, Glucose clamp technique, medicine.disease, 3. Good health, 030104 developmental biology, Endocrinology, Metabolism, Glucose, Receptors, Opioid, Glucose Clamp Technique, Female, business, medicine.drug |
| الوصف: | Although intensive glycemic control improves outcomes in type 1 diabetes mellitus (T1DM), iatrogenic hypoglycemia limits its attainment. Recurrent and/or antecedent hypoglycemia causes blunting of protective counterregulatory responses, known as hypoglycemia-associated autonomic failure (HAAF). To determine whether and how opioid receptor activation induces HAAF in humans, 12 healthy subjects without diabetes (7 men, age 32.3 ± 2.2 years, BMI 25.1 ± 1.0 kg/m2) participated in two study protocols in random order over two consecutive days. On day 1, subjects received two 120-min infusions of either saline or morphine (0.1 μg/kg/min), separated by a 120-min break (all euglycemic). On day 2, subjects underwent stepped hypoglycemic clamps (nadir 60 mg/dL) with evaluation of counterregulatory hormonal responses, endogenous glucose production (EGP, using 6,6-D2-glucose), and hypoglycemic symptoms. Morphine induced an ∼30% reduction in plasma epinephrine response together with reduced EGP and hypoglycemia-associated symptoms on day 2. Therefore, we report the first studies in humans demonstrating that pharmacologic opioid receptor activation induces some of the clinical and biochemical features of HAAF, thus elucidating the individual roles of various receptors involved in HAAF’s development and suggesting novel pharmacologic approaches for safer intensive glycemic control in T1DM. |
| اللغة: | English |
| تدمد: | 1939-327X 0012-1797 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::62135a77dc893f6ae0a20523ecbaa516Test http://europepmc.org/articles/PMC5652610Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....62135a77dc893f6ae0a20523ecbaa516 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1939327X 00121797 |
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