Somatostatin Receptor Antagonism Reverses Glucagon Counterregulatory Failure in Recurrently Hypoglycemic Male Rats
| العنوان: | Somatostatin Receptor Antagonism Reverses Glucagon Counterregulatory Failure in Recurrently Hypoglycemic Male Rats |
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| المؤلفون: | Aoibhe M. Pasieka, Richard Liggins, Owen Chan, Mahsa Jahangiriesmaili, Erin R. Mandel, Julian Aiken, Caylee A. Greenberg, Michael C. Riddell, Emily G. Hoffman, Ninoschka C. D’Souza, Trevor Teich |
| المصدر: | Endocrinology |
| بيانات النشر: | The Endocrine Society, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Blood Glucose, Male, medicine.medical_specialty, medicine.medical_treatment, Recurrent hypoglycemia, 030209 endocrinology & metabolism, Hypoglycemia, Peptides, Cyclic, Glucagon, Rats, Sprague-Dawley, 03 medical and health sciences, Hormone Antagonists, 0302 clinical medicine, Endocrinology, Recurrence, Diabetes mellitus, Internal medicine, Animals, Medicine, Somatostatin receptor 2, Receptors, Somatostatin, 030304 developmental biology, 0303 health sciences, Type 1 diabetes, business.industry, Insulin, medicine.disease, Liver Glycogen, Rats, 3. Good health, Glucose, Somatostatin, business, Research Article |
| الوصف: | Recent antecedent hypoglycemia is a known source of defective glucose counter-regulation in diabetes; the mechanisms perpetuating the cycle of progressive α-cell failure and recurrent hypoglycemia remain unknown. Somatostatin has been shown to suppress the glucagon response to acute hypoglycemia in rodent models of type 1 diabetes. We hypothesized that somatostatin receptor 2 antagonism (SSTR2a) would restore glucagon counterregulation and delay the onset of insulin-induced hypoglycemia in recurrently hypoglycemic, nondiabetic male rats. Healthy, male, Sprague–Dawley rats (n = 39) received bolus injections of insulin (10 U/kg, 8 U/kg, 5 U/kg) on 3 consecutive days to induce hypoglycemia. On day 4, animals were then treated with SSTR2a (10 mg/kg; n = 17) or vehicle (n = 12) 1 hour prior to the induction of hypoglycemia using insulin (5 U/kg). Plasma glucagon level during hypoglycemia was ~30% lower on day 3 (150 ± 75 pg/mL; P < .01), and 68% lower on day 4 in the vehicle group (70 ± 52 pg/mL; P < .001) compared with day 1 (219 ± 99 pg/mL). On day 4, SSTR2a prolonged euglycemia by 25 ± 5 minutes (P < .05) and restored the plasma glucagon response to hypoglycemia. Hepatic glycogen content of SSTR2a-treated rats was 35% lower than vehicle controls after hypoglycemia induction on day 4 (vehicle: 20 ± 7.0 vs SSTR2a: 13 ± 4.4 µmol/g; P < .01). SSTR2a treatment reverses the cumulative glucagon deficit resulting from 3 days of antecedent hypoglycemia in healthy rats. This reversal is associated with decreased hepatic glycogen content and delayed time to hypoglycemic onset. We conclude that recurrent hypoglycemia produces glucagon counterregulatory deficiency in healthy male rats, which can be improved by SSTR2a. |
| تدمد: | 1945-7170 0013-7227 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2cc5ac8cf735bbd9a572f9721d5f122dTest https://doi.org/10.1210/endocr/bqab189Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2cc5ac8cf735bbd9a572f9721d5f122d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19457170 00137227 |
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