Ignite Creation Date:
2024-05-06 @ 7:59 PM
Last Modification Date:
2024-10-26 @ 3:17 PM
Study NCT ID:
NCT06203275
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-01-12
First Post:
2023-11-17
Brief Title:
The G Protein-Coupled Receptor Kinase Type 2 Inhibitor Paroxetine as Adjunctive Therapy to Improve Insulin Sensitivity in Patients With Type 2 Diabetes Mellitus
Sponsor:
aya ramadan ashmawy sarhan
Organization:
Tanta University
Study Overview
Official Title:
The G Protein-Coupled Receptor Kinase Type 2 Inhibitor Paroxetine as Adjunctive Therapy to Improve Insulin Sensitivity in Patients With Type 2 Diabetes Mellitus
Status:
NOT_YET_RECRUITING
Status Verified Date:
2023-11
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:
The aim of this study is to investigate the effect of GRK2 inhibitor paroxetine on insulin resistance in patients with type 2 diabetes mellitus
Detailed Description:
Type 2 Diabetes Mellitus T2DM is one of the most common metabolic disorders worldwide and its development is primarily caused by a combination of two main factors including defective insulin secretion by pancreatic β-cells and the inability of insulin sensitive tissues to respond to insulin
Type 2 Diabetes Mellitus T2DM shares an intimate relationship with altered metabolism through the development of insulin resistance IR
The G protein-coupled receptor kinase type 2 GRK2 is involved in the regulation of many pivotal cell functions and is a key player in human health and diseasesIn fact GRK2 regulates insulin signaling through serine phosphorylated events G protein-coupled receptor kinase type 2 up-regulation inhibits insulin signaling and glucose extraction due to a time dependent insulin-stimulated association of GRK2 with Insulin Receptor Substrate 1 IRS1 leading to IRS1 serine phosphorylation and inactivation Inhibition of hepatic GRK2 expression is sufficient to improve glucose homeostasis and insulin sensitivity which eventually improves endothelial dysfunction in T2DM
Preclinical studies reported that genetic ablation of GRK2 in mice reduced insulin resistance In this sense inhibition of GRK2 activity could improve insulin sensitivity and might provide a new therapeutic target for the treatment of IR and T2DM Paroxetine an FDA-approved selective serotonin reuptake inhibitor SSRI was identified as a potent GRK2 inhibitor with higher selectivity for GRK2 over other GRKs both in vivo and in vitro
Paroxetine binds to the active site of GRK2 and stabilizes the kinase domain in a conformation that inhibits G protein-coupled receptor GPCR phosphorylation and desensitization6 A case report study demonstrated that during 3 months of paroxetine treatment 35-year-old woman with poorly controlled T2DM experienced an increased frequency of hypoglycemic episodes After discontinuation of paroxetine her awareness of hypoglycemia was dramatically improved The authors hypothesized that her hypoglycemic unawareness might be caused by autonomic dysfunction which is an atypical manifestation of serotonin syndrome Paroxetine also increased insulin sensitivity in non-diabetic patients who experienced remitted depression in a randomized trial
Type 2 Diabetes Mellitus T2DM shares an intimate relationship with altered metabolism through the development of insulin resistance IR
The G protein-coupled receptor kinase type 2 GRK2 is involved in the regulation of many pivotal cell functions and is a key player in human health and diseasesIn fact GRK2 regulates insulin signaling through serine phosphorylated events G protein-coupled receptor kinase type 2 up-regulation inhibits insulin signaling and glucose extraction due to a time dependent insulin-stimulated association of GRK2 with Insulin Receptor Substrate 1 IRS1 leading to IRS1 serine phosphorylation and inactivation Inhibition of hepatic GRK2 expression is sufficient to improve glucose homeostasis and insulin sensitivity which eventually improves endothelial dysfunction in T2DM
Preclinical studies reported that genetic ablation of GRK2 in mice reduced insulin resistance In this sense inhibition of GRK2 activity could improve insulin sensitivity and might provide a new therapeutic target for the treatment of IR and T2DM Paroxetine an FDA-approved selective serotonin reuptake inhibitor SSRI was identified as a potent GRK2 inhibitor with higher selectivity for GRK2 over other GRKs both in vivo and in vitro
Paroxetine binds to the active site of GRK2 and stabilizes the kinase domain in a conformation that inhibits G protein-coupled receptor GPCR phosphorylation and desensitization6 A case report study demonstrated that during 3 months of paroxetine treatment 35-year-old woman with poorly controlled T2DM experienced an increased frequency of hypoglycemic episodes After discontinuation of paroxetine her awareness of hypoglycemia was dramatically improved The authors hypothesized that her hypoglycemic unawareness might be caused by autonomic dysfunction which is an atypical manifestation of serotonin syndrome Paroxetine also increased insulin sensitivity in non-diabetic patients who experienced remitted depression in a randomized trial
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