Diabetes Mellitus Alters the Immuno-Expression of Neuronal Nitric Oxide Synthase in the Rat Pancreas

Int J Mol Sci. 2022 Apr 29;23(9):4974. doi: 10.3390/ijms23094974.

Abstract

Nitric oxide is generated from nitric oxide synthase following hyperglycemia-induced oxidative stress during the course of diabetes mellitus (DM). We examined the temporal immuno-expression of neuronal nitric oxide synthase (nNOS) in the pancreas of diabetic and non-diabetic rats using immunohistochemical, immunofluorescence and western blot techniques 12 h, 24 h, 1 week, 2 weeks, 1, 8 and 15 months after induction of DM. nNOS co-localized with pancreatic beta cells but disappears 12 h after the onset of DM. In contrast, the nNOS content of pancreatic nerves increased significantly (p < 0.001) 24 h after the induction of DM, and decreased sharply thereafter. However, nNOS-positive ganglion cells were observed even 15 months post-diabetes. ROS increased by more than 100% two months after the onset of DM compared to non-diabetic control but was significantly (p < 0.000001) reduced at 9 months after the induction of DM. The pancreatic content of GSH increased significantly (p < 0.02) after 9 months of DM. Although, TBARS content was significantly (p < 0.009; p < 0.002) lower in aged (9 months) non-diabetic and DM rats, TBARS rate was markedly (p < 0.02) higher 9 months after the induction of DM when compared to younger age group. In conclusion, nNOS is present in pancreatic beta cell, but disappears 12 h after the onset of diabetes. In contrast, the tissue level of nNOS of pancreatic nerves increased in the first week of diabetes, followed by a sharp reduction. nNOS may play important roles in the metabolism of pancreatic beta cell.

Keywords: ROS; TBARS; beta cell; diabetes; glutathione reductase; neural nitric oxide synthase; oxidative stress; pancreas.

MeSH terms

  • Animals
  • Diabetes Mellitus* / metabolism
  • Diabetes Mellitus* / pathology
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type I* / genetics
  • Nitric Oxide Synthase Type I* / metabolism
  • Pancreas / metabolism
  • Rats
  • Thiobarbituric Acid Reactive Substances

Substances

  • Thiobarbituric Acid Reactive Substances
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type I