P2X7R and P2X4R expression of mice submandibular gland in high-fat diet/streptozotocin-induced type 2 diabetes

Sci Rep. 2024 May 13;14(1):10855. doi: 10.1038/s41598-024-60519-3.

Abstract

Type 2 diabetes mellitus (T2DM) is a chronic inflammatory disease that can compromise the functioning of various organs, including the salivary glands (SG). The purinergic system is one of the most important inflammatory pathways in T2DM condition, and P2X7R and P2X4R are the primary purinergic receptors in SG that regulate inflammatory homeostasis. This study aimed to evaluate P2X7R and P2X4R expression, and morphological changes in the submandibular gland (SMG) in T2DM. Twenty-four 5-week-old mice were randomly assigned to control (CON) and diabetes mellitus (DM) groups (n = 12 each). Body weight, diet, and blood glucose levels were monitored weekly. The histomorphology of the SMG and the expression of the P2X7R, and P2X7R was evaluated by immunohistochemistry (IHC) staining and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) at 11 and 13 weeks of age. Our findings indicate a significant increase in food consumption, body weight, and blood glucose levels in the DM group. Although a significant increase in P2X7R and P2X4R expression was observed in the DM groups, the receptor location remained unchanged. We also observed a significant increase in the acinar area in the DM13w group, and a significant decrease in the ductal area in the DM11w and DM13w groups. Targeting purinergic receptors may offer novel therapeutic methods for diabetic complications.

Keywords: P2X4 purinergic receptor (P2X4R); P2X7 purinergic receptor (P2X7R); Submandibular gland (SMG); Type 2 diabetes mellitus (T2DM).

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Body Weight
  • Diabetes Mellitus, Experimental* / metabolism
  • Diabetes Mellitus, Experimental* / pathology
  • Diabetes Mellitus, Type 2* / metabolism
  • Diabetes Mellitus, Type 2* / pathology
  • Diet, High-Fat* / adverse effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Purinergic P2X4* / genetics
  • Receptors, Purinergic P2X4* / metabolism
  • Receptors, Purinergic P2X7* / genetics
  • Receptors, Purinergic P2X7* / metabolism
  • Streptozocin
  • Submandibular Gland* / metabolism
  • Submandibular Gland* / pathology

Substances

  • Receptors, Purinergic P2X4
  • Receptors, Purinergic P2X7
  • Blood Glucose
  • Streptozocin