Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05575206 |
| Other study ID # |
INCEPTOR |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
September 15, 2023 |
| Est. completion date |
March 1, 2025 |
Study information
| Verified date |
August 2023 |
| Source |
University Hospital Tuebingen |
| Contact |
Reiner Jumpertz-von Schwartzenberg, MD |
| Phone |
+49 7071 29 68934 |
| Email |
Reiner.Jumpertz-vs[@]med.uni-tuebingen.de |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial 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.
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
(e.g. 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.
