1. Hyperglucagonemia and type 2 diabetes
Type 2 diabetes pathophysiology is associated with increased fasting plasma levels of glucagon, contributing to the patients’ hyperglycemia. Following oral glucose consumption, glucagon levels are not suppressed like in healthy individuals, potentially contributing additionally to the postprandial hyperglycemia.
2. Glucagon receptor antagonism
Therefore, diabetic hyperglucagonemia has driven tremendous effort to develop clinical drugs to block the glucagon effects on the liver and thereby reduce endogenous glucose production. In the following mentioned PhD studies, we utilize a glucagon receptor antagonist as a physiologic tool to investigate the role of glucagon in different physiological settings (incretin effect, glucose excursions after a meal test and in combination with a DPP-4 and SGLT-2 inhibitor).
Pros and cons with glucagon receptor antagonism and liver-pancreas cross-talk
Glucagon receptor antagonism has been associated with deranged lipid plasma profiles, increased transaminases and hepatic steatosis in humans; Moreover, alpha-cell hyperplasia has been shown repeatedly in rodents.
Thus, we focus in ongoing studies at Clinical Metabolic Physiology and Yale University on the potential explanatory mechanism behind the effect on the liver and the liver-pancreas cross-talk.
Ph.d.-studies at Clinical Metabolic Physiology, SDCC:
1) Dissection of the gastrointestinal-mediated glucose disposal and incretin defect in patients with type 2 diabetes – the role of glucagon.
2) The role of glucagon signaling in the effects of dipeptidyl peptidase-4 inhibitors and sodium-glucose cotransporter-2 inhibitors.
Jan-Dec 2018 Postgraduate research studies at Yale University, Department of Endocrinology, School of Medicine.
Prof. Kitt F Petersen & Prof. Gerald Shulman.
1) Non-Invasive assessment of glucagon’s effects on hepatic glucose and mitochondrial metabolism using a glucagon receptor antibody
Co-investigator in PIONEER 6: A trial investigating the cardiovascular safety of oral semaglutide in subjects with type 2 diabetes.