Intestinal Region-Specific and Layer-Dependent Induction of TNF alpha in Rats with Streptozotocin-Induced Diabetes and after Insulin Replacement

Bódi, Nikolett and Chandrakumar, Lalitha and AL Doghmi, Afnan and Mezei, Diána and Szalai, Zita and Barta, Bence Pál and Balázs, János and Bagyánszki, Mária (2021) Intestinal Region-Specific and Layer-Dependent Induction of TNF alpha in Rats with Streptozotocin-Induced Diabetes and after Insulin Replacement. CELLS, 10 (9). ISSN 2073-4409

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Abstract

Tumour necrosis factor alpha (TNF alpha) is essential in neuroinflammatory modulation. Therefore, the goal of this study is to reveal the effects of chronic hyperglycaemia and insulin treatment on TNF alpha expression in different gut segments and intestinal wall layers. TNF alpha expression was mapped by fluorescent immunohistochemistry and quantitative immunogold electron microscopy in myenteric ganglia of duodenum, ileum and colon. Tissue TNF alpha levels were measured by enzyme-linked immunosorbent assays in muscle/myenteric plexus-containing (MUSCLE-MP) and mucosa/submucosa/submucous plexus-containing (MUC-SUBMUC-SP) homogenates. Increasing density of TNF alpha-labelling gold particles is observed in myenteric ganglia from proximal to distal segments and TNF alpha tissue levels are much more elevated in MUSCLE-MP homogenates than in MUC-SUBMUC-SP samples in healthy controls. In the diabetics, the number of TNF alpha gold labels is significantly increased in the duodenum, decreased in the colon and remained unchanged in the ileal ganglia, while insulin does not prevent these diabetes-related TNF alpha changes. TNF alpha tissue concentration is also increased in MUSCLE-MP homogenates of diabetic duodenum, while decreased in MUC-SUBMUC-SP samples of diabetic ileum and colon. These findings support that type 1 diabetes has region-specific and intestinal layer-dependent effects on TNF alpha expression, contributing to the regional damage of myenteric neurons and their intestinal milieu.

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