Track topics on Twitter Track topics that are important to you
The common genetic variation at rs8004664 in the FOXN3 gene is independently and significantly associated with fasting blood glucose, but not insulin, in non-diabetic humans. Recently, we reported that primary hepatocytes from rs8004664 hyperglycemia risk allele carriers have increased FOXN3 transcript and protein levels and liver-limited overexpression of human FOXN3, a transcriptional repressor that had not been implicated in metabolic regulation previously, increases fasting blood glucose in zebrafish. Here, we find that injection of glucagon into mice and adult zebrafish decreases liver Foxn3 protein and transcript levels. Zebrafish foxn3 loss-of-function mutants have decreased fasting blood glucose, blood glucagon, liver gluconeogenic gene expression, and α cell mass. Conversely, liver-limited overexpression of foxn3 increases α cell mass. Supporting these genetic findings in model organisms, non-diabetic rs8004664 risk allele carriers have decreased suppression of glucagon during oral glucose tolerance testing. By reciprocally regulating each other, liver FOXN3 and glucagon control fasting glucose.
This article was published in the following journal.
Name: Cell reports
The secretion of glucagon is controlled by blood glucose and inappropriate secretion of glucagon contributes to hyperglycaemia in diabetes. Besides its role in glucose regulation, glucagon regulates a...
Glucagon dysregulation is an essential component in the pathophysiology of type 2 diabetes. Studies in vitro and in animal models have shown that zinc co-secreted with insulin suppresses glucagon secr...
We aim to investigate the relationship between serum somatostatin (SST) levels and glucose-lipid metabolism at various stages of glucose tolerance in the Jino ethnic minority (n=111) and Han populatio...
The respective contributions to endogenous glucose production (EGP) of the liver, kidney and intestine vary during fasting. We previously reported that the deficiency in either hepatic or intestinal g...
Embedded into a complex signaling network coordinating glucose uptake, usage and production, the nuclear bile acid receptor FXR is expressed in several glucose-processing organs including the liver wh...
The most prevalent monogenetic diabetic subtype is named maturity onset diabetes of the young type (MODY3) or hepatocyte nuclear factor 1α (HNF1A)-diabetes. The aim of this study is to ev...
In normal physiology, glucagon from pancreatic alpha cells plays an important role in maintaining glucose homeostasis via its regulatory effect on hepatic glucose production. Patients with...
Peripheral glucagon action increases hepatic glucose production. In rodents hypothalamic action of glucagon paradoxically suppresses glucose production. Intranasally administered peptides ...
Incretinbased treatment of patients with type 2 diabetes mellitus (T2DM) has increasing interest. The incretin glucagon-like peptide-1 (GLP-1) stimulates beta-cells to increased secretion ...
Patients with diabetes are characterised not only by compromised insulin secretion and action, but also by elevated plasma levels of the 29-amino acid peptide hormone glucagon, which hithe...
Hepatocyte nuclear factor 1-alpha is a transcription factor found in the LIVER; PANCREAS; and KIDNEY that regulates HOMEOSTASIS of GLUCOSE.
Cell surface receptors that bind glucagon with high affinity and trigger intracellular changes which influence the behavior of cells. Activation of glucagon receptors causes a variety of effects; the best understood is the initiation of a complex enzymatic cascade in the liver which ultimately increases the availability of glucose to body organs.
A test to determine the ability of an individual to maintain HOMEOSTASIS of BLOOD GLUCOSE. It includes measuring blood glucose levels in a fasting state, and at prescribed intervals before and after oral glucose intake (75 or 100 g) or intravenous infusion (0.5 g/kg).
G-PROTEIN COUPLED CELL SURFACE RECEPTORS that bind GLUCAGON-LIKE PEPTIDES and are expressed by cells in pancreatic, intestinal, and neural tissues. These receptors regulate cellular responses to BLOOD GLUCOSE, INSULIN, and INFLAMMATION signals.
A peptide of 36 or 37 amino acids that is derived from PROGLUCAGON and mainly produced by the INTESTINAL L CELLS. GLP-1(1-37 or 1-36) is further N-terminally truncated resulting in GLP-1(7-37) or GLP-1-(7-36) which can be amidated. These GLP-1 peptides are known to enhance glucose-dependent INSULIN release, suppress GLUCAGON release and gastric emptying, lower BLOOD GLUCOSE, and reduce food intake.
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...