Glucose‐dependent insulinotropic polypeptide–producing K cells in dexamethasone‐treated rats

Abstract

SummarySome studies indicate that diabetes mellitus exerts an influence on the gastrointestinal tract and its diffuse neuroendocrine system (DNES) in regard to cellular density and neuroendocrine content. Since there is no data about relationship between experimentally induced non-insulindependent (type 2) diabetes mellitus (NIDDM) on the gut K cells, the aim of our study was to investigate immunohistochemical, stereological and ultrastructural changes of rat K cells after 12 days of dexamethasone treatment. Twenty male Wistar rats aged 30 days were given daily intraperitoneally 2 mg kg -1 dexamethasone (group DEX, 10 rats) or saline (group C, 10 rats) for 12 days. Tissue specimens were obtained from each antrum with corpus and different parts of the small (SI) and large intestine (LI) of all animals. Immunohistochemistry was carried out using antisera against the GIP and insulin. Transmission electron microscopy was also used. Although, according to the literature data, rat K cells are present in the duodenum and jejunum and, to a lesser extent, in the ileum, in the present study we observed that those cells were abundant also in all parts of the LI. We observed generally that GIP-producing K cells were augmented in all parts of SI and decreased in the LI of DEX rats. Insulin immunoreactivity (ir) coexpressed with GIP-ir in K cells and was stronger in the SI of DEX rats as compared with C rats. We also found by electron microscopy that small intestinal K cells have features not only of GIPsecreted but also of insulin-secreted cells. We concluded that dexamethasone treatment caused proliferation of K cells in the rat SI, and simultaneously transformation of GIP-producing K cells to insulin-synthesizing cells.

Investigation of the mechanisms contributing to the compensatory increase in insulin secretion during dexamethasone-induced insulin resistance in rhesus macaques

“…In this study, short-term administration of dexamethasone resulted in a twofold increase in mealstimulated GIP excursions compared with control conditions, but modestly decreased postprandial GLP-1 excursions. These data are in agreement with previous work by Koko et al (2008) demonstrating that 12 days of treatment with dexamethasone in Wistar rats increased intestinal K-cell numbers. Of note, fasting plasma GIP concentrations did not differ between treatments, whereas fasting plasma insulin concentrations were increased fourfold with dexamethasone treatment.…”

“…Several mechanisms for glucocorticoid-induced increases in glucose-stimulated insulin secretion have been proposed in the literature, including increases in circulating incretin hormones (Koko et al 2008) and enhanced parasympathetic input to the islet (Angelini et al 2010). In this study, short-term administration of dexamethasone resulted in a twofold increase in mealstimulated GIP excursions compared with control conditions, but modestly decreased postprandial GLP-1 excursions.…”

Immunohistochemical study of enteric nervous system in dexamethasone-treated rats

“…Generally, the observed changes in the number, density and ultrastructure of the gut endocrine cells in our previous reports (KOKO et al, 2001;GLIŠIĆ et al, 2006;KOKO et al, 2008;GLIŠIĆ et al, 2011) as well as the changes in the ENS in the dexamethasone-treated rats, presented in this study, indicate a likely disturbed bowel motility and secretion. The disturbance of the gut motility and secretion interfere with normal metabolic processes of food digestion, which may lead to impaired glucose homeostasis and the development of other symptoms and complications of diabetes mellitus type 2.…”