Long-term high sugar and fat exposure changes hormone receptor levels and hormone release in identical insulin-producing cells

Prolonged exposure to glucotoxic and lipotoxic conditions impaired insulin release in response to both GIP and GLP-1 in clonal BRIN BD11 cells.

• Glucotoxic conditions for 48 hours significantly impaired insulin release in response to GIP and GLP-1 (p < 0.05 to p < 0.001).
• Lipotoxic conditions for 18 hours reduced the insulin-releasing effect of GIP, but not GLP-1.
• Both GIP and GLP-1 insulin-releasing actions were compromised after 48 hours of lipotoxic culture (p < 0.05 to p < 0.01).
• Glucolipotoxic culture completely annulled the insulinotropic action of GIP after 18 hours, while GLP-1 effects remained similar to control.
• After 48 hours of glucolipotoxic culture, both GIP- and GLP-1-mediated effects were significantly impaired (p < 0.05 to p < 0.001).
• Gene expression for GIP and GLP-1 receptors increased under glucotoxic conditions but decreased following glucolipotoxic exposure.

Simplified