Cytosolic phosphoenolpyruvate carboxykinase is expressed in alpha-cells from human and murine pancreas

Abstract

The pancreatic islets of Langerhans, mainly formed by glucagon-producing alpha-cells and insulin-producing beta-cells, are critical for glucose homeostasis. Insulin and glucagon oppositely modulate blood glucose levels in health, but a combined decline in insulin secretion together with increased glucagon secretion contribute to hyperglycemia in diabetes. Despite this bi-hormonal dysregulation, most studies have focused on insulin secretion and much less is known about glucagon secretion. Therefore, a deeper understanding of alpha-cell metabolism and glucagon secretion is of great interest. Here, we show that phosphoenolpyruvate carboxykinase (PCK1), an essential cataplerotic enzyme involved in metabolism and long considered to be absent from the pancreatic islet, is expressed in pancreatic alpha-cells of both murine and human. Furthermore, PCK1 transcription is induced by fasting and diabetes in rat pancreas, which indicates that the PCK1 activity is required for alpha-cell adaptation to different metabolic states. To our knowledge, this is the first evidence implicating PCK1 expression in alpha-cell metabolism.

The pancreatic islets of Langerhans, mainly formed by glucagon-producing alpha-cells and insulin-producing beta-cells, are critical for glucose homeostasis. Insulin and glucagon oppositely modulate blood glucose levels in health, but a combined decline in insulin secretion together with increased glucagon secretion contribute to hyperglycemia in diabetes. Despite this bi-hormonal dysregulation, most studies have focused on insulin secretion and much less is known about glucagon secretion. Therefore, a deeper understanding of alpha-cell metabolism and glucagon secretion is of great interest. Here, we show that phosphoenolpyruvate carboxykinase (PCK1), an essential cataplerotic enzyme involved in metabolism and long considered to be absent from the pancreatic islet, is expressed in pancreatic alpha-cells of both murine and human. Furthermore, PCK1 transcription is induced by fasting and diabetes in rat pancreas, which indicates that the PCK1 activity is required for alpha-cell adaptation to different metabolic states. To our knowledge, this is the first evidence implicating PCK1 expression in alpha-cell metabolism.