Related Experiment Video

Updated: Apr 11, 2026

Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease
08:15

Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease

Published on: May 10, 2024

1.0K

Towards a genotype-based approach for a patient-centered pharmacologic therapy of type 2 diabetes

André J Scheen1

  • 1Division of Clinical Pharmacology, Center for Interdisciplinary Research on Medicines (CIRM), University of Liège, Liège, Belgium.

Annals of Translational Medicine
|June 6, 2015
PubMed

Insights

Genetic differences in alpha-2 adrenoceptors (α2AAR) impact insulin secretion in type 2 diabetes. Blocking α2AAR with yohimbine improved insulin secretion in patients with a specific genetic risk variant.

Area of Science:

  • Endocrinology
  • Genetics
  • Pharmacology

Background:

  • Genetic variations in alpha-2 adrenoceptors (α2AAR) may explain inconsistent findings on α2AAR antagonists' effects on insulin secretion and glucose control in type 2 diabetes.
  • The ADRA2A gene single-nucleotide polymorphism rs553668 has been associated with varying responses to treatments targeting α2AAR.

Purpose of the Study:

  • To investigate the functional impact of the ADRA2A rs553668 risk variant on insulin secretion.
  • To evaluate the efficacy of yohimbine, an α2AAR antagonist, in improving insulin secretion in type 2 diabetes patients with the risk variant.

Main Methods:

  • Confirmation of the risk variant's effect on insulin secretion using human pancreatic islets.
  • Assessment of yohimbine's effect on insulin secretion during an oral glucose tolerance test in patients stratified by genotype.

Main Results:

  • The A allele of rs553668 was confirmed to be associated with defective insulin secretion in human pancreatic islets.
  • Yohimbine administration dose-dependently improved reduced insulin secretion in patients carrying the risk variant during an oral glucose tolerance test.

Conclusions:

  • Genetic heterogeneity of alpha-2 adrenoceptors (α2AAR) influences therapeutic responses in type 2 diabetes.
  • Genotype-guided intervention, specifically using α2AAR antagonists like yohimbine, shows promise for personalized treatment strategies in type 2 diabetes.
Keywords:
Alpha-2 adrenoceptor (α2AAR)genotypeinsulin secretionpersonalized medicinetype 2 diabetes

More Related Videos

An In Ovo Model for Testing Insulin-mimetic Compounds06:09

An In Ovo Model for Testing Insulin-mimetic Compounds

Published on: April 23, 2018

11.3K
A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging09:37

A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging

Published on: July 14, 2016

8.9K

Related Concept Videos

Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
91
Diabetes: Management and Pharmacotherapy01:15

Diabetes: Management and Pharmacotherapy

The therapy for diabetes aims to alleviate hyperglycemia-related symptoms, prevent acute metabolic decompensation, and reduce chronic end-organ complications. Glycemic control is evaluated through short-term (self-monitoring, continuous glucose monitoring) and long-term (A1c, fructosamine) metrics, enabling near real-time tracking of blood glucose levels and reflecting glycemic control over specific time frames.
Insulin remains the cornerstone of treatment for most patients with type 1 and many...
1.5K
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
125
Pharmacogenetics and Pharmacogenomics: Overview01:29

Pharmacogenetics and Pharmacogenomics: Overview

Pharmacogenetics and pharmacogenomics examine how genetic factors influence an individual's response to drugs. While pharmacogenetics focuses on the impact of specific genetic variants on drug effects, pharmacogenomics takes a broader approach, studying how genetic variation across populations contributes to differences in drug responses. These fields aim to explain why individuals may experience varying levels of efficacy or adverse reactions to the same medication.Variability in drug...
174
Pharmacogenetics of Drug Metabolism: Overview01:27

Pharmacogenetics of Drug Metabolism: Overview

Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...
148
Diabetes Mellitus: Type 2 and Gestational01:22

Diabetes Mellitus: Type 2 and Gestational

Type 2 diabetes, characterized by insulin resistance, arises when the insulin receptors on cells lose responsiveness to insulin, diminishing the cell's capacity to take up glucose, resulting in elevated blood glucose levels. To receive a diagnosis of Type 2 diabetes, a series of blood glucose tests are necessary to assess whether the blood glucose falls within normal parameters. If the result is out of the normal range, a patient may be diagnosed as prediabetic or diabetic, depending on the...
5.8K