Impaired counterregulation during hypoglycemia in type 1 diabetes (T1D) is partly due to inadequate pancreatic islet alpha-cell glucagon secretion. We hypothesized that hypoglycemia can be prevented in autoimmune T1D by selective somatostatin receptor type 2 (SSTR2) antagonism of alpha cells to relieve SSTR2 inhibition, thereby increasing glucagon secretion. Diabetic biobreeding diabetes prone (BBDP) rats (D) vs non-diabetic BBDP (N) rats, underwent infusion of vehicle or SSTR2 antagonist (SSTR2a) during insulin-induced hypoglycaemia. D rats, treated with SSTR2a, needed little or no glucose to maintain hypoglycemia. To monitor real-time glucagon secretory response directly, we developed the technique of thin slices of the pancreas from D and N rats as well as normal human pancreas, subjected to perifusion with vehicle vs SSTR2a. SSTR2a treatment enhanced glucagon secretion in N and D rats and human pancreas. We conclude that SSTR2 antagonism can enhance hypoglycemia-stimulated glucagon release sufficient to achieve normoglycemic control.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OTU.1807/35619 |
| Date | 12 July 2013 |
| Creators | Karimian, Negar |
| Contributors | Gaisano, Herbert Young, Vranic, Mladen |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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