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Updated: Oct 30, 2025

Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain
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Systemic Administration of Insulin Receptor Antagonist Results in Endothelial and Perivascular Adipose Tissue

Bartosz Proniewski1, Anna Bar1, Anna Kieronska-Rudek1,2

  • 1Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Bobrzynskiego 14, 30-348 Krakow, Poland.

Cells
|July 2, 2021
PubMed

Insights

Short-term hyperglycemia impairs blood vessel function and protective perivascular adipose tissue (PVAT) in mice. This dysfunction contributes to vascular issues in diabetes, even without obesity.

Area of Science:

  • Vascular Biology
  • Metabolic Syndrome
  • Adipose Tissue Research

Background:

  • Diabetes-associated hyperglycemia causes endothelial dysfunction.
  • Perivascular adipose tissue (PVAT) plays a crucial role in maintaining vascular health.
  • Understanding the interplay between hyperglycemia, endothelium, and PVAT is vital for diabetes research.

Purpose of the Study:

  • To investigate the effects of short-term, experimentally induced hyperglycemia on endothelial function and PVAT.
  • To assess the impact of insulin receptor antagonism on nitric oxide (NO) production and vascular health.
  • To determine the role of PVAT dysfunction in hyperglycemia-induced vascular pathology.

Main Methods:

  • Administration of S961 peptide (insulin receptor antagonist) to induce hyperglycemia in mice.
  • In vivo assessment of endothelial function using magnetic resonance imaging.
  • Ex vivo analysis of nitric oxide (NO) production via electron paramagnetic resonance spectroscopy.
  • Analysis of PVAT, aortic segments, and plasma biomarkers.

Main Results:

  • Short-term hyperglycemia severely impaired NO-dependent endothelial function.
  • PVAT lost its vasoprotective function in both thoracic and abdominal aortas.
  • Adiponectin expression and UCP1-positive area in PVAT were reduced, particularly in the thoracic aorta.
  • Vascular pathology occurred in the absence of obesity or fat overload.

Conclusions:

  • Dysfunctional PVAT significantly contributes to vascular pathology in conditions of altered insulin signaling.
  • Experimental hyperglycemia disrupts the protective role of PVAT, exacerbating endothelial dysfunction.
  • These findings highlight PVAT as a key player in diabetes-related vascular complications.
Keywords:
endothelial functioninsulin receptor antagonistmagnetic resonance imagingperivascular adipose tissue

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