Morphological and biochemical observations on hepatic glycogen metabolism in genetically diabetic (db/db) mice

Changes in hepatocyte glycogen morphology, liver glycogen, and blood glucose and insulin levels were studied at various time points after initiation of feeding in 10 week old genetic diabetic (db/db) mice (n = 8) and their lean littermates adapted to a controlled feeding regimen (6 h fed - 18 h fast). In spite of hyperinsulinemic (insulin greater than or equal to 97.60 +/- 88 uU/ml) and hyperglycemic (glucose greater than or equal to 437.1 +/- 49.5 mg/dl) conditions favoring glycogen synthesis, feeding-induced hepatic glycogen deposition was less efficient in the diabetic mice. An apparent decreased ability to mobilize hepatic glycogen during fasting and maintenance of relatively high fasting liver glycogen concentrations were however attributable to the anti-glycogenolytic effects of high blood glucose and insulin concentrations. Histochemical determinations (PAS) on livers of db/db mice showed typical lobular patterns of glycogen distribution during deposition and depletion of the polysaccharide. At stages of maximum glycogen (6 h after initiation of feeding), periportal cells displayed intensely stained masses of glycogen with centrilobular cells staining more diffusely. Ultrastructural studies revealed smooth endoplasmic reticulum (SER) in close association with glycogen during its deposition and depletion. The preservation of normal glycogen morphology and SER-glycogen ultrastructure indicates that functioning of the SER in hepatic glycogen metabolism is normal in midly diabetic (db/db) mice.