Ignite Creation Date:
2024-05-06 @ 6:10 PM
Last Modification Date:
2024-10-26 @ 2:43 PM
Study NCT ID:
NCT05575206
Status:
RECRUITING
Last Update Posted:
2023-09-25
First Post:
2022-09-26
Brief Title:
The Influence of Genetic Variations in ELAPOR1 or ELAPOR2 on Insulin Secretion and Glucose Regulation in Humans
Sponsor:
University Hospital Tuebingen
Organization:
University Hospital Tuebingen
Study Overview
Official Title:
Untersuchung Des Einflusses Von Genetischen Varianten in ELAPOR1 Oder ELAPOR2 Auf Die Insulinsekretion Und Glukoseregulation im Menschen
Status:
RECRUITING
Status Verified Date:
2023-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Insulin resistance and the depletion of insulin secretion are major pathogenetic aspects of type 2 diabetes mellitus Recently inceptor a receptor on the surface of beta cells was dicovered Inceptor promotes beta cell resistance to insulin and IGF-1
In humans the inceptor is encoded by the two genes ELAPOR1 and ELAPOR2 Whether functional mutations in these genes affect insulin secretion and glucose regulation in humans has not been investigated so far
In this study we investigate the influence of genetic variations in ELAPOR1 or ELAPOR2 on insulin secretion and glucose regulation in humans by hygerglycemic glucose clamp technique and oral glucose tolerance test respectively
In humans the inceptor is encoded by the two genes ELAPOR1 and ELAPOR2 Whether functional mutations in these genes affect insulin secretion and glucose regulation in humans has not been investigated so far
In this study we investigate the influence of genetic variations in ELAPOR1 or ELAPOR2 on insulin secretion and glucose regulation in humans by hygerglycemic glucose clamp technique and oral glucose tolerance test respectively
Detailed Description:
Type 2 diabetes mellitus is a heterogenic disorder with a complex pathogenesis Although loss of beta cell function is crucial for the manifestation of the disease Genome-wide association studies identified more than 400 genetic variations associated with a reduced beta cell function Interestingly beta cells are not only responsible for the secretion of insulin but are also insulin sensitive cells whereby insulin secretion and proliferation is regulated It is well known that an insulin and insulin-like growth factor IGF-1 resistance lead to the manifestation of type 2 diabetes Underlying mechanism are mostly unknown Recently a new receptor on the surface of beta-cells was identified which mediates the resistance of beta cells to insulin and IGF-1 This insulin inhibitory receptor Inceptor induces its inhibitory function via clathrin-mediated endocytosis of the INSR-IGF-1R complex In mice inceptor is encoded by lir and its knock-out leads to beta cell proliferation and an increased insulin secretion In animal models treatment with monoclonal antibodies against the extracellular domain of inceptor leads to a significantly improved glucose regulation Thus pharmacological interventions on the inceptor could represent a novel therapeutic approach for the treatment of type 2 diabetes mellitus In humans inceptor is encoded by genes ELAPOR1 and ELAPOR2 So far there are no studies in humans that investigate if functional mutations in these genes affect insulin secretion and glucose regulation The aim of this study is to investigate whether subjects with genetic variants in ELAPOR1 or ELAPOR2 have altered insulin secretion and thus altered glucose regulation For this purpose the study results are compared with a reference cohort without variants in ELAPOR1 or ELAPOR2 matched for age sex waist to hip ratio and BMI from our databases of previous studies eg PLIS NCT01947595 PREG NCT04270578 KNOMA NCT04950283 Insulin secretion is assessed by hyperglycemic glucose clamp technique An oral glucose tolerance test will be performed to assess glucose tolerance
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None