Multiorgan insulin sensitivity in lean and obese subjects

Area of Science:

• Metabolic Physiology
• Endocrinology
• Obesity Research

Background:

• Insulin resistance is a hallmark of obesity, affecting glucose and lipid metabolism.
• Understanding multiorgan insulin sensitivity is crucial for metabolic health assessment.

Purpose of the Study:

• To comprehensively assess multiorgan insulin sensitivity in lean versus obese individuals with normal glucose tolerance.
• To determine the impact of varying physiological insulin concentrations on glucose and lipid metabolism.

Main Methods:

• Utilized the hyperinsulinemic-euglycemic clamp technique with stable isotope tracers.
• Infused insulin at low, medium, and high physiological concentrations in 40 obese and 26 lean subjects.
• Measured endogenous glucose production (R(a)), palmitate R(a), and glucose disposal (R(d)).

Main Results:

• Obese subjects exhibited reduced suppression of endogenous glucose production and palmitate R(a) compared to lean subjects at low insulin doses.
• Stimulation of glucose disposal was significantly lower in obese individuals across all tested insulin concentrations.
• At high insulin levels, differences in glucose and palmitate R(a) suppression between groups diminished, but glucose disposal remained lower in obese subjects.

Conclusions:

• Endogenous glucose production and lipolysis are highly sensitive to insulin, while muscle glucose uptake requires higher insulin levels.
• Physiological hyperinsulinemia can overcome insulin resistance in the liver and adipose tissue but not in skeletal muscle of obese individuals with normal glucose tolerance.
• Skeletal muscle insulin resistance is a key metabolic defect in obesity that persists despite compensatory mechanisms in other organs.