Association of glucagon‐like peptide‐1 receptor‐targeted imaging probe with in vivo glucagon‐like peptide‐1 receptor agonist glucose‐lowering effects
Open Access
- 23 April 2020
- journal article
- research article
- Published by Wiley in Journal of Diabetes Investigation
- Vol. 11 (6), 1448-1456
- https://doi.org/10.1111/jdi.13281
Abstract
Aims and Introduction Glucagon‐like peptide‐1 receptor agonists (GLP‐1RA) are used for treatment of type 2 diabetes mellitus worldwide. However, some patients don’t respond well to the therapy and cautions must be taken for certain patients including those with reduced insulin secretory capacity. Thus, it is clinically important to predict the efficacy of GLP‐1RA therapy. To visualize and quantify β‐cells, GLP‐1R‐targeted imaging has emerged recently. We investigated whether GLP‐1R‐targeted imaging can predict the efficacy of GLP‐1RA treatment. Materials and Method: We developed 111Indium‐labeled exendin‐4 derivative (111In‐Ex4) as a GLP‐1R‐targeting probe. Diabetic mice were selected from NONcNZO10/LtJ male mice that were fed for different durations with 11%‐fat chow. After 3‐week administration of dulaglutide as GLP‐1RA therapy, mice with non‐fasting blood glucose levels under and over 300 mg/dL were defined as responders and non‐responders, respectively. In addition, ex‐vivo 111In‐Ex4 pancreatic accumulations (111In‐Ex4 pancreatic values) were examined. Results The non‐fasting blood glucose levels after treatment were 172.5±42.4 mg/dL in responders (n=4) and 330.8±20.7 mg/dL in non‐responders (n=5), respectively. Ex‐vivo 111In‐Ex4 pancreatic values showed significant correlations with post‐treatment glycohemoglobin and glucose area under curve (AUC) during oral glucose tolerance test (R2=0.76 and 0.80; pex‐vivo 111In‐Ex4 pancreatic values was 1.00 (pEx‐vivo 111In‐Ex4 pancreatic values reflected dulaglutide efficacy, suggesting clinical possibilities for expanding GLP‐1R‐targeted imaging applications.Keywords
This publication has 27 references indexed in Scilit:
- Oral glucose-stimulated serum C-peptide predicts successful switching from insulin therapy to liraglutide monotherapy in Japanese patients with type 2 diabetes and renal impairmentJournal of Diabetes Investigation, 2013
- Retrospective analysis of safety and efficacy of insulin-to-liraglutide switch in Japanese type 2 diabetes: A caution against inappropriate use in patients with reduced β-cell functionJournal of Diabetes Investigation, 2013
- Liraglutide administration in type 2 diabetic patients who either received no previous treatment or were treated with an oral hypoglycemic agent showed greater efficacy than that in patients switching from insulinJournal of Diabetes Investigation, 2012
- Incretin-Based Therapies for Type 2 Diabetes Mellitus: Properties, Functions, and Clinical ImplicationsAmerican Journal Of Medicine, 2011
- GLP-1 receptor antagonist as a potential probe for pancreatic β-cell imagingBiochemical and Biophysical Research Communications, 2009
- Functional Assessment of Pancreatic β-Cell Area in HumansDiabetes, 2009
- Hyperglycemia, maturity-onset obesity, and insulin resistance in NONcNZO10/LtJ males, a new mouse model of type 2 diabetesAmerican Journal of Physiology-Endocrinology and Metabolism, 2007
- Downregulation of GLP-1 and GIP Receptor Expression by HyperglycemiaDiabetes, 2007
- Type 2 Diabetes-a Matter of ß-Cell Life and Death?Science, 2005
- U.K. Prospective Diabetes Study 16: Overview of 6 Years' Therapy of Type II Diabetes: A Progressive DiseaseDiabetes, 1995