The brain plays a major role in controlling our blood glucose levels. In type 2 diabetics this glucose metabolism brain control is often dysfunctional. Genetic components for this phenomenon have so far remained elusive. A group of scientists have now shown in the Journal of Clinical Investigations that in men a genetic variant of the gene DUSP8 can increase the risk for type 2 diabetes by impairing our brain response to the hormone insulin.
Insulin is a pancreatic hormone that controls our blood sugar levels. Insulin not only stimulates the uptake of glucose from blood into peripheral tissues, it also acts on the brain, specifically the hypothalamus, to control glucose and energy metabolism. In obese subjects, insulin loses some of its activity due to the activation of inflammatory signaling and a subsequent impairment of the cellular response downstream to the insulin receptor. This phenomenon, termed insulin resistance, is a major hallmark in the development of type 2 diabetes, but to date not yet fully understood. Recent genome-wide association studies (GWAS) identified DUSP8 as type 2 diabetes risk gene. Now, scientists have investigated how the protein Dusp8 (dual-specificity phosphatase 8), which is encoded by the DUSP8 gene, regulates glucose tolerance and insulin sensitivity.
"Carriers of a genetic variant of the gene DUSP8 were shown to have a moderately increased risk for type 2 diabetes, but the functional importance of Dusp8 for the etiology of the disease remained unknown," explains the lead author of the study. "By combining cellular models, Dusp8 loss- and gain-of-function mice and functional magnetic resonance imaging (fMRI) of humans with genetic variants in the gene DUSP8, we now exposed a specific role of the protein Dusp8 as a gatekeeper for systemic glucose tolerance and hypothalamic insulin sensitivity," adds the senior author.
The protein Dusp8 has a regulatory effect on inflammatory processes in the hypothalamus and on the hypothalamic-pituitary-adrenal (HPA) axis. It seems to protect the organism against hyper-activation of inflammatory signaling and impaired insulin sensitivity in the hypothalamus. The scientists could show that the deletion of the Dusp8 gene in male but not in female mice increased hypothalamic inflammation, impaired HPA axis feedback and increased basal stress hormone levels, which all together aggravated the insulin sensitivity. The sex-specific role of murine Dusp8 was consistent with fMRI data in human volunteers that revealed reduced hypothalamic insulin sensitivity in male but not female carriers of the DUSP8 type 2 diabetes risk variant.
In future studies, the researchers want to investigate the effect of central insulin action and the DUSP8 type 2 diabetes risk variant on the hypothalamic-pituitary-adrenal axis in human subjects with or without T2D.
https://www.dzd-ev.de/en/press/press-releases/press-releases-2020/a-gatekeeper-against-insulin-resistance-in-the-brain/index.html
https://www.jci.org/articles/view/136363
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Ftype-2-diabetes-risk&filter=22
How a genetic variant increase the risk for type 2 diabetes in men
- 1,922 views
- Added
Edited
Latest News
Which of the two DNA strand…
By newseditor
Posted 16 Jun
Microglia depletion prevent…
By newseditor
Posted 16 Jun
Colorectal cancer stem cell…
By newseditor
Posted 16 Jun
Paranoia in the brain
By newseditor
Posted 16 Jun
In-vitro 3D culture of func…
By newseditor
Posted 15 Jun
Other Top Stories
Bacteria use traffic-cop-like mechanism to infect gut
Read more
A faster and cheaper way to produce new antibiotics
Read more
A device for rapid diagnosis of bacterial infections
Read more
Zika virus may cause microcephaly by hijacking human immune molecule
Read more
The mechanism of regulation of hepatitis C viral propagation and pa…
Read more
Protocols
Bioengineered human colon o…
By newseditor
Posted 14 Jun
Development of an efficient…
By newseditor
Posted 12 Jun
A co-culture system of macr…
By newseditor
Posted 10 Jun
Analysis of 3D pathology sa…
By newseditor
Posted 08 Jun
Long-term expandable mouse…
By newseditor
Posted 07 Jun
Publications
The Thermodynamics of Mind
By newseditor
Posted 17 Jun
Lost in translation: challe…
By newseditor
Posted 17 Jun
Pathways for macrophage upt…
By newseditor
Posted 16 Jun
Common and distinct neural…
By newseditor
Posted 16 Jun
Strand-resolved mutagenicit…
By newseditor
Posted 16 Jun
Presentations
Myelin plasticity in the ve…
By newseditor
Posted 10 Jun
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar