Thioredoxin-1 Overexpression in the Ventromedial Nucleus of the Hypothalamus Preserves the Counterregulatory Response to Hypoglycemia During Type 1 Diabetes in Male Rats
| Autor: | Chunxue Zhou, Vanessa H. Routh |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Blood Glucose Male medicine.medical_specialty animal structures Complications endocrine system diseases Endocrinology Diabetes and Metabolism medicine.medical_treatment Recurrent hypoglycemia Hypothalamus Hypoglycemia Real-Time Polymerase Chain Reaction Diabetes Mellitus Experimental Rats Sprague-Dawley 03 medical and health sciences Thioredoxins Internal medicine Diabetes mellitus Internal Medicine medicine Animals Type 1 diabetes Chemistry Insulin nutritional and metabolic diseases medicine.disease Streptozotocin Rats 030104 developmental biology Ventromedial nucleus of the hypothalamus Endocrinology Diabetes Mellitus Type 1 Glucose Ventromedial Hypothalamic Nucleus medicine.drug |
| Zdroj: | Diabetes |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | We previously showed that the glutathione precursor, N-acetylcysteine (NAC), prevented hypoglycemia-associated autonomic failure (HAAF) and impaired activation of ventromedial hypothalamus (VMH) glucose-inhibited (GI) neurons by low glucose after recurrent hypoglycemia (RH) in nondiabetic rats. However, NAC does not normalize glucose sensing by VMH GI neurons when RH occurs during diabetes. We hypothesized that recruiting the thioredoxin (Trx) antioxidant defense system would prevent HAAF and normalize glucose sensing after RH in diabetes. To test this hypothesis, we overexpressed Trx-1 (cytosolic form of Trx) in the VMH of rats with streptozotocin (STZ)-induced type 1 diabetes. The counterregulatory response (CRR) to hypoglycemia in vivo and the activation of VMH GI neurons in low glucose using membrane potential sensitive dye in vitro was measured before and after RH. VMH Trx-1 overexpression normalized both the CRR and glucose sensing by VMH GI neurons in STZ rats. VMH Trx-1 overexpression also lowered the insulin requirement to prevent severe hyperglycemia in STZ rats. However, like NAC, VMH Trx-1 overexpression did not prevent HAAF or normalize activation of VMH GI neurons by low glucose in STZ rats after RH. We conclude that preventing HAAF in type 1 diabetes may require the recruitment of both antioxidant systems. |
| Databáze: | OpenAIRE |
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