Developmental stage modifies diet-induced peripheral insulin resistance in rats

Area of Science:

• Metabolic Physiology
• Nutritional Science
• Aging Research

Background:

• Age and dietary composition are critical determinants of glucose homeostasis.
• Understanding their interplay is crucial for metabolic health, especially concerning insulin sensitivity.

Purpose of the Study:

• To investigate the independent and combined effects of age and diet on glucose metabolism and tissue-specific glucose uptake (R'g).
• To elucidate how different diets (high-starch, high-fat, high-sucrose) influence glucose uptake across various ages in male Sprague-Dawley rats.

Main Methods:

• Male Sprague-Dawley rats of different ages (weanling, young, mature, older) were fed specific diets for 5 weeks.
• Glucose disappearance and tissue-specific glucose uptake (R'g) were measured under basal and hyperinsulinemic, euglycemic conditions.
• Key metabolic parameters including free fatty acids, triglycerides, glucose-6-phosphate, and glycogen synthase activity were analyzed.

Main Results:

• Significant age effects were observed on basal and clamp free fatty acid and triglyceride concentrations.
• Both age and diet significantly affected basal skeletal muscle R'g, with an age-associated increase in high-fat diet fed rats.
• Insulin-stimulated muscle R'g was reduced by both age and diet, with age-related decreases in glucose-6-phosphate and glycogen synthase activity.

Conclusions:

• Diet-induced alterations in peripheral glucose metabolism are significantly modulated by the aging process.
• Age plays a critical role in determining the response of glucose uptake to dietary interventions, impacting both basal and insulin-stimulated conditions.
• These findings highlight the complex interaction between aging and diet in regulating glucose metabolism.