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Intestinal glucagon-like peptide-1: A new player associated with impaired counterregulatory responses to

Fang-Xin Jin1, Yan Wang1, Min-Ne Li1

  • 1Department of Histology and Embryology, Key Laboratory of Universities in Shandong Province, Shandong Second Medical University, Weifang 261053, Shandong Province, China.

World Journal of Diabetes
|August 28, 2024
PubMed
Abstract

Insights

Excessive intestinal glucagon-like peptide-1 (GLP-1) impairs the body's ability to counteract low blood sugar in type 1 diabetes. This leads to reduced counterregulatory hormone secretion and a weakened stress response during hypoglycemia.

Area of Science:

  • Endocrinology
  • Metabolic Disorders
  • Diabetes Research

Background:

  • Impaired hypoglycaemic counterregulation is a significant clinical concern for individuals with diabetes, often leading to treatment hesitancy.
  • The precise mechanisms underlying hypoglycaemic counterregulation dysfunction remain incompletely understood.
  • Glucagon-like peptide-1 (GLP-1) analogues are used in type 1 diabetes mellitus (T1DM), but GLP-1's role in counterregulatory dysfunction during hypoglycemia is unreported.

Purpose of the Study:

  • To investigate the influence of intestinal glucagon-like peptide-1 (GLP-1) on impaired hypoglycaemic counterregulation in a mouse model of type 1 diabetes mellitus (T1DM).

Main Methods:

  • Type 1 diabetes mellitus (T1DM) was induced in mice using streptozotocin, followed by insulin injections to model recurrent hypoglycemia (DH5).
  • Immunofluorescence, Western blot, and ELISA were used to assess the impact of intestinal GLP-1 on the sympathetic-adrenal reflex and glucagon (GCG) secretion.
  • GLP-1 receptor agonist or antagonist were administered via ileal infusion or intraperitoneal injection to elucidate the role of intestinal GLP-1.

Main Results:

  • Recurrent hypoglycemia (DH5) significantly increased intestinal GLP-1 and GLP-1 receptor (GLP-1R) expression.
  • Excessive intestinal GLP-1 weakened the sympathetic-adrenal reflex and impaired adrenal counterregulation during hypoglycemia.
  • DH5 mice exhibited increased pancreatic δ-cell mass, somatostatin, and cAMP in δ cells, but decreased cAMP in α cells and plasma GCG levels, indicating disrupted hormonal signaling.

Conclusions:

  • Elevated intestinal GLP-1 is closely linked to impaired counterregulatory responses during hypoglycemia in T1DM.
  • This impairment results in reduced appetite and diminished secretion of key counterregulatory hormones including adrenaline, noradrenaline, and glucagon (GCG).
Keywords:
Glucagon-like peptide-1Impaired hypoglycaemic counterregulationIntestinePancreasType 1 diabetes

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