Specific Glucagon Assay System Using a Receptor-Derived Glucagon-Binding Peptide Probe

Sep 30, 2026

Uploaded by Stanley

Glucagon is a pancreatic peptide hormone that raises blood glucose and is central to diabetes onset and homeostasis, yet accurate quantification is difficult because structural similarity to other hormones drives antibody cross-reactivity. Rapid, specific glucagon detection is critical during hypoglycemia. This study develops glucagon-specific, peptide-based fluorescent probes by screening glucagon-binding peptides from the glucagon receptor sequence via peptide array, enabling detection within 30 minutes at nanomolar sensitivity. The probes show higher specificity than conventional antibody approaches, offering proof-of-concept for rapid assays, with further optimization needed for physiological and clinical validation.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Abstract

Introduction

Article Specific Glucagon Assay System Using a Receptor-Derived Glucagon-Binding Peptide Probe Hajime Shigeto 1, *, Yoshio Suzuki 2 and Shohei Yamamura 1, * Academic Editor: Konstantin K. Turoverov Received: 25 November 2025 Revised: 26 December 2025 Accepted: 31 December 2025 Published: 4 January 2026 Copyright: © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. 1 Health and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 2217-14 Hayashi-cho, Takamatsu 761-0395, Japan 2 Health and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 6, 1-1-1 Higashi, Tsukuba 305-8566, Japan; [suzuki-yoshio@aist.go.jp](suzuki-yoshio@aist.go.jp) * [Correspondence: hajime.shigeto@aist.go.jp](Correspondence: hajime.shigeto@aist.go.jp) (H.S.); [yamamura-s@aist.go.jp](yamamura-s@aist.go.jp) (S.Y.) Abstract Glucagon is a peptide hormone secreted by pancreatic alpha cells which elevates blood glucose and plays a critical role in diabetes onset and homeostasis. The accurate assessment of glucagon concentration is challenging due to its structural similarity with other hormones, causing cross-reactivity in antibody-based methods. Rapid and specific glucagon detection is essential, particularly during hypoglycemia. This study aimed to develop glucagon-specific probes combining high specificity, rapid detection, and ease of operation. We designed novel peptide-based probes by screening glucagon-binding peptides from the glucagon receptor sequence using a peptide array method. This strategy, based on receptor amino acid sequences, can be applied to the identification of binding peptides for other hormones, expanding its potential utility. The screened peptides were conjugated with fluorescent dyes to create probes enabling detection within 30 min. The developed probes demonstrated superior specificity for glucagon relative to similar sequence analogs compared with conventional antibody-based methods, with detection limits in the nanomolar range. This study represents a proof-of-concept approach for rapid and highly specific glucagon detection. However, further optimization of probe sensitivity and validation under physiological conditions will be required before clinical or diagnostic application. These improvements in the probe’s properties will enable the reliable blood glucagon detection and accurate diagnostic assessment of diabetes-related diseases. Keywords: glucagon; glucagon receptor; biosensor 1. Introduction Glucagon is a peptide hormone secreted by pancreatic alpha cells (α-cells) in response to low blood glucose levels. Glucagon induces the degradation of glycogen accumulated in the cells into glucose to increase blood glucose levels [1–7] . Mouse model studies have shown that both the inhibition of glucagon signaling and insulin secretion does not result in the diabetes phenotype [8–10] . These results indicate that glucagon contributes more to the maintenance of blood glucose concentrations than insulin. Additionally, in individuals with type 1 diabetes, α-cell dysfunction leads to impaired glucagon secretion, compromising the counter-regulatory response to low glucose levels and increasing the risk of severe hypoglycemic events [11] . The precise and rapid quantification of circulating glucagon is therefore critical for optimizing glycemic control and mitigating acute complications. However, the significance of glucagon was not established until recently because of difficulty of its accurate detection using conventional methods. Glucagon is matured from proglucagon through enzymatic cleavage. Various peptides with similar amino acid sequences are produced from proglucagon depending on their cleavage sites [12,13] . Therefore, antibodybased detection methods (

FAQs

Why is measuring glucagon concentration challenging?

Accurate assessment is difficult because glucagon is structurally similar to other hormones, leading to cross-reactivity in antibody-based methods.

How did the researchers design the glucagon-specific probes?

They screened glucagon-binding peptides from the glucagon receptor sequence using a peptide array method, then conjugated the selected peptides with fluorescent dyes.

How fast and how sensitive is the developed detection approach?

The fluorescent probes enable detection within 30 minutes and achieve detection limits in the nanomolar range.

Sep 30, 2026

Uploaded by Stanley