Detemir

To determine whether observations from Gck mutant mice (and GCK-MODY humans) were related to altered GCK activity in pancreatic β-cells or other sites such as brain, we examined responses to hypoglycemia in I366F mice with β-cells ablated by streptozotocin (STZ). Starting at age 3 weeks, female I366F mice received a single ip dose of 200 mg/kg of STZ and were monitored for the development of hyperglycemia. We aimed to create a model of insulin-dependent diabetes while avoiding uncontrolled hyperglycemia in animals and matching glycemic exposure prior to studying. To achieve this, where diabetes developed, mice were treated with once daily insulin levemir (Detemir, NovoNordisk, Crawley, UK) with insulin doses adjusted in individual animals according to tail-vein sampling aiming for glucose values of approximately 15 mM. After 5 weeks of therapy, animals underwent surgery and clamp studies as described below.