Glutamine dipeptide and cortisol change the liver glucose metabolism and reduce the severity of insulin-induced hypoglycaemia in untreated T1DM Swiss mice

Abstract

Context: Glutamine is conditionally essential in type 1 diabetes mellitus, and might be useful to counteract hypoglycaemia. Objective: To investigate the systemic and hepatic effects of counter-regulatory hormones and glutamine dipeptide (GDP) during hypoglycemic episodes. Materials and methods: Diabetic Swiss mice made hypoglycaemic by insulin injection (1 U/kg) were given counter-regulatory hormones and/or GDP. Sixty minutes later, liver histology, liver glucose metabolism and plasma were assessed. Results: Combined, cortisol and GDP improved the hypoglycemic profile. During liver perfusion, gluconeogenesis was possibly the major pathway leading to glucose release. Perfusion with gluconeogenic precursors after glycogen depletion by adrenaline increased liver glucose and urea release. Discussion: The less severe hypoglycaemia could result from cortisol stimulating periportal gluconeogenesis and GDP inhibiting pericentral glycogenolysis, both favouring liver glucose release. Conclusions: At least some benefits of GDP and cortisol during hypoglycaemia came from their hepatic actions, and their use in diabetic patients should be explored.

• Type 1 diabetes mellitus
• glucose homeostasis
• counter-regulation
• liver perfusion
• gluconeogenesis

Acknowledgements

The authors thank the technical assistance of ER Santos, M Fabricio and VS Romão.

Declaration of interest

The authors report no declaration of interest.