Plasma glucose concentration determines direct versus indirect liver glycogen synthesis

Area of Science:

• Metabolic Physiology
• Hepatology
• Carbohydrate Metabolism

Background:

• Hepatic glycogenesis is crucial for glucose homeostasis.
• The direct and indirect pathways contribute differently to glycogen synthesis.
• Understanding these pathways' regulation is vital for metabolic research.

Purpose of the Study:

• To determine hepatic glycogenesis via direct and indirect pathways as a function of glucose infusion rate.
• To investigate the impact of varying glucose loads on glycogen synthesis in rats.

Main Methods:

• Conscious, catheterized rats fasted for 48 hours were infused with glucose containing tracers ([U-14C]- and [6-3H]glucose).
• Glucose infusion rates ranged from 0 to 230 mumol X min-1 X kg-1 over 3 hours.
• Plasma glucose, lactate, insulin, and hepatic glycogen deposition were measured.

Main Results:

• Hepatic glycogen deposition rate remained constant across a wide range of glucose infusion rates.
• The direct pathway's contribution to glycogen synthesis increased with glucose infusion rate (13% to 74%).
• Endogenous glucose production was suppressed, and only a small fraction of infused glucose entered the direct pathway.

Conclusions:

• The relative contribution of direct and indirect pathways of hepatic glycogen synthesis is dependent on glucose load and plasma glucose concentration.
• The indirect pathway predominates at physiological post-feeding plasma glucose concentrations.
• This highlights the complex regulation of liver glycogen storage.