Intermittent fasting protects β-cell identity and function in a type-2 diabetes model.

Area of Science:

• Endocrinology
• Metabolic Diseases
• Nutritional Science

Background:

• Type 2 diabetes (T2DM) involves genetic and environmental factors, leading to hyperglycemia, impaired insulin secretion, and insulin resistance.
• Chronic hyperglycemia negatively impacts pancreatic beta-cell function, mass, and identity.
• Intermittent fasting (IF) shows metabolic benefits, but its specific effects on pancreatic beta-cells in T2DM models are not fully understood.

Purpose of the Study:

• To investigate the long-term effects of intermittent fasting (IF) on pancreatic beta-cell function and identity in mouse models of type 2 diabetes (T2DM).
• To elucidate the mechanisms by which IF may protect beta-cells and improve metabolic parameters in T2DM.

Main Methods:

• KK and KKA ^y mice, models of polygenic T2DM, were subjected to intermittent fasting (IF) for 16 weeks.
• Evaluated parameters included blood glucose, plasma insulin, body weight, lipid profiles, insulin sensitivity, and expression of key beta-cell transcription factors.
• Assessed glucose-stimulated insulin secretion and hepatic steatosis, gluconeogenesis, and inflammation.

Main Results:

• IF significantly reduced blood glucose and plasma insulin levels, decreased body weight gain, and improved insulin sensitivity in both KK and KKA ^y mice.
• IF enhanced the expression of beta-cell identity markers (NKX6.1, MAFA, PDX1) and decreased a marker of dedifferentiation (ALDH1a3).
• IF normalized glucose-stimulated insulin secretion and reduced hepatic steatosis and inflammation, particularly in KKA ^y mice.

Conclusions:

• Intermittent fasting (IF) preserves pancreatic beta-cell identity and function in T2DM mouse models.
• IF confers metabolic benefits, including improved glycemic control and insulin sensitivity, and reduces hepatic complications.
• IF represents a potential dietary intervention for managing T2DM by protecting beta-cell health.