Cytosolic phosphoenolpyruvate carboxykinase is expressed in α‐cells from human and murine pancreas

Abstract

The pancreatic islets of Langerhans, mainly formed by glucagon-producing α-cells and insulin-producing β-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 α-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 α-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 α-cell adaptation to different metabolic states. To our knowledge, this is the first evidence implicating PCK1 expression in α-cell metabolism. K E Y W O R D Sdiabetes, glucagon, insulin, pancreatic α-cell, PCK1

Laser Capture Microdissection Coupled Capillary Immunoassay to Study the Expression of PCK-2 on Spatially-Resolved Islets of Rat Langerhans

“…In normal rodent islets, β-cells forming the core surrounded by other endocrine cells in the periphery [49]. In this study, attention was placed on Langerhans islets mainly for β cells whereas α-cells were omitted during laser cutting of border area for each Langerhans islet [19]. which was further confirmed by qPCR analysis of PCK-1 and PCK-2.…”

“…Interestingly, pancreatic β-cells do not express PCK1 but only PCK2 [15,46]. PCK1 has been shown to be present within α-cells of Langerhans islets localized on the surface of the islets [19].…”

“…Under the supervision of a histologist, Langerhans islets were selected and dissected from the slides. In order to collect predominantly β-cells but not α-cells, we have omitted the cutting of a border area for each Langerhans islet [19]. For each rat, Langerhans islets were pooled until the total section area reached more than 0.8 mm 2 and subsequently, protein or RNA was isolated.…”

Integrated Metabolomics and Transcriptomic Analysis of Hepatopancreas in Different Living Status Macrobrachium nipponense in Response to Hypoxia

“…As an indispensable enzyme in the gluconeogenic pathway, PEPCK has been regarded as essential in humans and mice [ 38 , 39 ]. Interestingly, compared with the previous transcriptome analysis, four PEPCK genes were found in the joint analysis of the metabolome and transcriptome [ 13 ].…”

Evaluation of the inhibitory potentials of selected compounds from Costus spicatus (Jacq.) rhizome towards enzymes associated with insulin resistance in polycystic ovarian syndrome: an in silico study

“…In diabetic patients, an altered rate of gluconeogenesis is responsible for increased hepatic glucose output (HGO) and therefore sustained hyperglycemia is observed in both insulin-dependent DM and non-insulin-dependent DM [10]. Expression of the gene for cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) in pancreatic α-cells is induced during diabetes, both in animals and in human patients [11]. α-Amylase is responsible for postprandial glucose levels and has become a therapeutic target for the management of T2DM through inhibition to decrease the reabsorption of glucose in the intestine and postprandial blood glucose levels [12].…”