Research & Publications
Dr. Samuel focuses on the underlying mechanisms by which ectopic lipid accumulation in the liver leads to insulin resistance and increases gluconeogenesis. Dysregulation of insulin signaling and hepatic glucose production account for two of the most common clinical findings in patients with diabetes: impaired glucose tolerance and fasting hyperglycemia. Hepatic insulin resistance arises when an increase in hepatic sn 1,2 diacylglycerol activated protein kinase c epsilon which then impairs hepatic insulin receptor kinase activation. This proximal defect in insulin signaling impacts all downstream pathways tied to insulin signaling. The regulation of gluconeogenesis is more complex. This is an incredibly malleable pathway that is influenced by multiple hormonal signals and substrate inputs. One mechanism that has emerged is the post-translational modification of pyruvate carboxylase. An increase in PC protein content may enhance the capacity for gluconeogenesis and in turn offers the possibility of developing novel therapies.
Diabetes Mellitus, Type 2; Gluconeogenesis; Insulin Resistance; Pyruvate Carboxylase; Non-alcoholic Fatty Liver Disease