Morphological and biochemical observations on hepatic glycogen metabolism in mice on a controlled feeding schedule. II. Streptozotocin-diabetic mice.

Abstract

Morphological aspects of hepatic glycogen metabolism in streptozotocin (SZ) diabetic mice on a controlled feeding cycle (6 hr fed, 18 hr fasted) were studied and correlated with plasma glucose and insulin levels at various time intervals after feeding. Hepatic glycogen was low at initiation of feeding (approximately 0.05%) and increased to a maximum of 4.54 +/- 0.30% (N = 8) as compared to 6.90 +/- 0.20% (N = 12) in normal animals. Plasma glucose levels were similar to those of normal mice at initiation of feeding (80 +/- 5 mg/dl) but much higher during the feeding period (diabetic: 540 +/- 15 mg/dl, normal: 150 +/- 10 mg/dl). At the end of the feeding period, plasma glucose levels rapidly declined, reaching lower than normal levels. In contrast to insulin responses to feeding in normal animals, plasma insulin levels in SZ-diabetic mice remained very low, never exceeding 16 muU/ml. At maximum hepatic glycogen deposition, light microscopic studies showed atypical patterns of glycogen distribution with periportal cells having generally smaller-than-normal glycogen masses. Ultrastructural studies indicated that these cells contained more abundant quantities of smooth endoplasmic reticulum (SER) than is characteristically seen. The aberrant distribution patterns of glycogen observed in the diabetic mice provided morphological evidence for the proposal that the SER is involved in hepatic glycogenesis, with insulin deficiency resulting in abnormal functioning of the organelle.