Endocrine Abstracts

Introduction: Severe hypoglycemia induced by sulfonylurea overdose is a result of insulin hypersecretion. Pasireotide (SOM230) is a multireceptor-targeted somatostatin analogue with high affinity for somatostatin receptor subtypes sstr₁,₂,₃ and especially sstr₅, which are expressed on rat and human β cells; pasireotide has been shown to inhibit insulin secretion in both species. The aim of these studies was to investigate the effect of pasireotide on glyburide (glibenclamide)-induced hypoglycemia in fasted male Lewis rats.

Methods: Adult male Lewis rats (n=6 per group) were fasted for 24 h and received glyburide 30 mg/kg by oral gavage alone (group 1) or in combination with pasireotide 10 or 30 μg/kg by s.c. injection (groups 2 and 3, respectively). Blood samples were taken by sublingual bleeding 1 h before treatment and 1, 3 and 6 h after treatment. Glucose levels were measured using Accu-check.

Results: Overall, 24 h food restriction significantly reduced plasma glucose levels from 8.0±0.4 mmol/l on day −1 to 6.4±0.3, 6.1±0.4 and 6.1±0.2 mmol/l at 1, 3 and 6 h, respectively, on day 1. Following glyburide application in group 1, plasma glucose levels were further reduced to 5.5±0.2, 4.2±0.2 and 3.5±0.4 mmol/l at 1, 3 and 6 h after application. Co-application of glyburide with pasireotide 10 μg/kg in group 2 resulted in glucose plasma levels of 7.0±0.4, 6.2±0.4 and 6.5±0.5 mmol/l at 1, 3 and 6 h after application. In group 3, co-application of glyburide with pasireotide 30 μg/kg resulted in plasma glucose values that were close to those seen in non-fasted animals (ranging between 7.0 and 7.6 mmol/l) 1–6 h after the application.

Conclusion: In rats with glyburide-induced hypoglycemia, low-dose pasireotide increased plasma glucose levels to those seen in fasted rats, and high-dose pasireotide resulted in plasma glucose values similar to those seen in non-fasted rats. These preclinical results suggest that pasireotide may have a role in managing patients with severe hypoglycemia induced by excessive insulin levels, such as those due to glyburide overdose.

Declaration of interest: I fully declare a conflict of interest. Details below.

Funding: This work was supported, however funding details unavailable.