Insulin and IGF-1 Receptors in A Human Intestinal Adenocarcinoma Cell Line (Caco-2): Regulation of Na⁺Glucose Transport Across the Brush Border

Abstract

Both insulin and IGF-1 receptors are present in intestinal mucosal cells, although their role in this tissue is unclear. We have characterized these receptors in a human adenocarcinoma cell line, Caco-2, and examined their role in the regulation of glucose transport and absorption in these cells. The Caco-2 cells demonstrated specific insulin and IGF-1 receptors. They also bound cytochalasin B, suggesting the presence of a glucose transporter-like protein. When grown on membranes, the Caco-2 cells formed columnar, bipolar cells with tight junctions. The monolayer selectively transported D-glucose and methyl-D-glucose, with complete exclusion of L-glucose, D-mannitol and inulin. The absorption of glucose across the monolayer occurred via a Na+/glucose cotransporter, as indicated by a change in short circuit current after addition of glucose to the apical membrane. When examined under several conditions, neither insulin nor IGF-1 had an affect on the transport of glucose across the Caco-2 monolayer, nor the production of lactate by the cells. It is concluded that the insulin and IGF-1 receptors of Caco-2 cells do not regulate glucose transport.

PepT1-mediated epithelial transport of dipeptides and cephalexin is enhanced by luminal leptin in the small intestine

“…However, intrajejunal leptin did not alter the flux of glucose, water, or electrolytes, thus demonstrating that this control of di-and tripeptide transport was independent of water, electrolyte, and glucose fluxes (48). This observation is line with data showing that insulin treatment does not affect glucose transport (49), but increases dipeptide transport in Caco-2 cells (24). Therefore, it appears that leptin increase of peptide transport is likely to involve PepT1.…”

Regulation of expression of the intestinal oligopeptide transporter (Pept-1) in health and disease

“…The stimulation was rapid (within 60 min) and required binding of insulin to its membrane receptor, because preventing this binding abolished the stimulatory effect of insulin on dipeptide transport (52). Lastly, the stimulation in dipeptide transport appeared to be specific, because insulin did not have any effect on glucose transport by Caco-2 cells (29).…”

Hyperinsulinaemia and hyperglycaemia: possible risk factors of colorectal cancer among diabetic patients

“…Insulin-like growth factor-1 (IGF-1) inhibits apoptosis and is required for cell cycle progression [19]. Both normal colorectal epithelium and colon cancer tissue have insulin and IGF-1 receptors [20,21]; upon activation by IGF-1, the receptor-ligand complex inhibits apoptosis with continuation of the cell cycle [16,17,18,21]. Therefore, both pre-maligant and cancerous stages can be affected by IGF-1.…”