Morphological and biochemical observations on hepatic glycogen metabolism in mice on a controlled feeding schedule. I. Normal mice.

Changes in hepatocyte morphology were correlated with chemically measured liver glycogen, blood glucose, and plasma insulin levels in control-fed mice (6 hr fed, 18 hr fasted) sacrificed at various time intervals after initiation of a 6-hr meal. At initiation of feeding hepatic glycogen was low(0.05%) but deposition proceeded rapidly, reaching a maximum of 6.99 +/- 0.13% by the sixth hour. Glycogen was depleted during the subsequent fasting period, reaching the prefeeding levels by 24 hr. A relative hyperglycemia (140-192 mg/100/ ml) predominated during all stages of glycogen deposition and depletion until the 21st hour. Plasma insulin levels were maximum during feeding (63 +/- 7 microU/ml, 3 hr) with mild hyperinsulinemia (insulin greater than 16 microU/ml) occurring during glycogen depletion (9-21 hr). Histochemical determinations (PAS) showed lobular patterns of hepatic glycogen which correlated with chemically measured glycogen levels. Six hours after initiation of feeding, periportal cells showed intensely stained masses of glycogen while centrilobular cells showed relatively diffuse staining. At 24 hours after initiation of feeding (18 hr of fasting), no significant staining was observed in the hepatocytes. Ultrastructurally, during all stages of glycogen deposition and depletion, centrilobular cells were characterized by the presence of dispersed glycogen particles with elements of smooth endoplasmic reticulum (SER) between the particles, while periportal cells showed dense glycogen deposits with SER restricted to the periphery of the glycogen masses.