Intestinal functions in Goto-Kakizaki (GK) rat

• Grant number: 23/11437-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2023
• End date: November 30, 2024
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Rui Curi
• Grantee: Thais Martins Rodrigues
• Host Institution: Centro de Ciências Biológicas e da Saúde. Universidade Cruzeiro do Sul (UNICSUL). São Paulo , SP, Brazil
• Associated research grant: 18/09868-7 - Cellular and molecular mechanisms of insulin resistance and inflammation in obese Wistar rats and lean Goto-Kakizaki rats: causes and associations with diet and physical exercise, AP.TEM

Abstract

Type 2 diabetes mellitus (T2DM) is characterized by peripheral insulin resistance and hyperglycemia. Although obesity is the main factor in the development of T2DM, a considerable proportion of patients are not obese. The Goto-Kakizaki (GK) rat is a model of T2DM and develops peripheral insulin resistance, hyperglycemia and chronic inflammation spontaneously, without obesity. Results from the group indicate that the GK rat shows marked differences in the gastrointestinal tract, the small intestine, when compared to the control Wistar. The GK rat shows intestinal remodeling, with hypertrophy of the muscular layer in the duodenum, jejunum, and ileum, accompanied by inflammation, compared to the control Wistar. There is an alteration in the morphology of the villi and crypts, which may compromise intestinal functions, nutrient and water absorption, and hormone secretion. The small intestine performs digestion of nutrients and absorption of metabolites and water while the large intestine performs absorption of water and electrolytes. Intestinal motility is controlled by the myenteric enteric nervous system (ENS) while secretions are regulated by the submucosal enteric nervous system. The gut also produces and secretes hormones that control gut functions as well as insulin secretion (incretins). Alterations in gut morphology and inflammation may be associated with impaired glucose and water absorption, but also incretin secretion and epithelial integrity of the GK rat gut. The aim of the present study is to study intestinal functions in the GK rat by assessing gene expression, by polymerase chain reaction (RT-qPCR), of markers of intestinal functions: glucose transporter type 2 (GLUT-2), sodium-glucose co-transporter 1 (SGLT1); water transporters, aquaporins 3 and 8 (AQP3 and AQP8); incretins: gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1); mucin-2 (MUC2), interleukin-22 (IL22) and zonulin, markers of intestinal epithelium integrity, repair and permeability, respectively, in 21-, 60- and 120-day-old GK rats.