In developed countries, many health-related problems are caused by a disruption of the metabolic balance between glucose synthesis and energy utilization in the liver.
Researchers have discovered the molecular mechanisms which disturb the metabolic balance between these two different but linked processes. This study appears to be helpful as it identifies the treatment for non-alcoholic fatty liver disease (NAFLD) and diabetes.
A well-regulated process “energy homeostasis” depends on the coordination between the feeding behavior and energy expenditure. In recent years the control of energy homeostasis in the body has gained much attention due to changes caused by the onset of conditions such as diabetes and obesity.
The findings of the study are published in journal Nature.
Glucagon is the hormone that is released from the pancreas. It plays a crucial role in maintaining the glucose level of the blood. When the blood glucose level falls below the normal range then it triggers the liver to convert the glycogen (the storage form of glucose) into glucose. The liver converts glycogen into glucose through a process known as gluconeogenesis. Glucose is the main fuel for the brain. Diabetes is characterized by a high blood glucose level in which metabolic balance is disrupted.
Gerald Shulman, a senior author and Rachel Perry, the first author of the study lead the Yale team. They reported that the mechanism of glucagon action for maintaining a metabolic balance between the glucose production and utilization of energy in the liver has identified.
Gerald Shulman who is the George R. Cowgill Professor of Medicine and professor of cellular and molecular physiology said that through innovative methods scientists assess the metabolic action of the liver which makes them able to define the molecular mechanisms of glucagon action.
Perry who is an assistant professor of cellular and molecular physiology and medicine said that previous studies showed that by focusing on glucagon researchers only tried to reduce the high blood glucose level in diabetic patients. But through those treatments, many severe side effects have resulted such as a buildup of enzymes in the liver which lead to fatty liver disease.
The recent study highlights the role of calcium within the mitochondria which is the powerhouse of the cell as it produces the energy for the cellular activities.
Scientists discovered a protein known as inositol triphosphate receptor 1 (INSP3R1) in the cell. This protein involved in regulating two processes in the liver i.e. gluconeogenesis and liver fat oxidation that occurs in response to glucagon. The action of gluconeogenesis is influenced when INSP2R1 regulates the signaling of calcium within the cell. This protein also maintains fat oxidation by influence calcium signaling in the mitochondria.
Perry further added that when the calcium signaling is regulated in the mitochondria it potentially increases the positive effects of glucagon by promoting the mitochondrial fat oxidation within the liver and it also reverses the factors that enhance the NAFLD without inducing the negative effects in the process of gluconeogenesis.
During the lab experiments, scientists treated the obese rodents with glucagon and as a result, this hormone reversed the NFLD. It also improves the sensitivity of insulin in the body. When the obese mice who lack INSP2R1 were treated chronically with glucagon then hormone showed no effect in the body.
The authors concluded by saying that these findings provide new perceptions about the glucagon action and elaborate on the action of calcium transport within the mitochondria which is regulated by INSP3R1. This may open new ways for generating the novel therapies which are used to reverse type 2 diabetes and NAFLD.