Systemic Metabolic Alterations Correlate with Islet-Level Prostaglandin E 2 Production and Signaling Mechanisms That Predict β-Cell Dysfunction in a Mouse Model of Type 2 Diabetes
The transition from β-cell compensation to β-cell failure is not well understood. Previous works by our group and others have demonstrated a role for Prostaglandin EP3 receptor (EP3), encoded by the gene, in the loss of functional β-cell mass in Type 2 diabetes (T2D). The primary endogenous EP3 liga...
Saved in:
Published in | Metabolites Vol. 11; no. 1 |
---|---|
Main Authors | , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
16.01.2021
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | The transition from β-cell compensation to β-cell failure is not well understood. Previous works by our group and others have demonstrated a role for Prostaglandin EP3 receptor (EP3), encoded by the
gene, in the loss of functional β-cell mass in Type 2 diabetes (T2D). The primary endogenous EP3 ligand is the arachidonic acid metabolite prostaglandin E
(PGE
). Expression of the pancreatic islet EP3 and PGE
synthetic enzymes and/or PGE
excretion itself have all been shown to be upregulated in primary mouse and human islets isolated from animals or human organ donors with established T2D compared to nondiabetic controls. In this study, we took advantage of a rare and fleeting phenotype in which a subset of Black and Tan BRachyury (BTBR) mice homozygous for the
mutation-a strong genetic model of T2D-were entirely protected from fasting hyperglycemia even with equal obesity and insulin resistance as their hyperglycemic littermates. Utilizing this model, we found numerous alterations in full-body metabolic parameters in T2D-protected mice (e.g., gut microbiome composition, circulating pancreatic and incretin hormones, and markers of systemic inflammation) that correlate with improvements in EP3-mediated β-cell dysfunction. |
---|---|
ISSN: | 2218-1989 2218-1989 |
DOI: | 10.3390/metabo11010058 |