Insulin action during fasting and refeeding in rat determined by euglycemic clamp

Area of Science:

• Endocrinology
• Metabolic Research
• Physiology

Background:

• Insulin is a key regulator of glucose metabolism.
• Fasting significantly alters glucose homeostasis.
• Understanding insulin's role during fasting and refeeding is crucial for metabolic health.

Purpose of the Study:

• To investigate the impact of fasting and subsequent refeeding on insulin sensitivity in rats.
• To characterize alterations in hepatic glucose production and peripheral glucose utilization in response to insulin.

Main Methods:

• Euglycemic-hyperinsulinemic clamps were performed in control, 3-day fasted, and 3-day fasted then 3-day refed rats.
• Radioactive glucose ([3-3H]glucose) was used to measure glucose production and utilization.
• Insulin concentrations were varied to assess dose-response effects.

Main Results:

• Hepatic glucose production was suppressed by insulin in control and refed rats but not in fasted rats, even at high insulin levels.
• Maximal glucose utilization and insulin-stimulated glucose clearance were reduced in fasted rats compared to controls.
• Three days of refeeding largely restored normal insulin responses for glucose utilization.

Conclusions:

• Fasting induces a state of insulin unresponsiveness at both hepatic and peripheral levels.
• Refeeding for three days effectively restores normal insulin sensitivity.
• These findings underscore the profound metabolic adaptations to fasting and the recovery process with nutritional replenishment.