Effects of glucagon on hepatic microsomal glucose-6-phosphatase in vivo.
The smooth endoplasmic reticulum (SER) has been implicated in glycogen deposition and depletion. It has been suggested that SER proliferation plays a role in elevated glucose release during rapid glycogenolysis (Striffler et al., Am. J. Anat. 160: 363, 1981). In these studies, the role of SER in glucagon-stimulated hepatic glucose release was examined by assessing changes in microsomal glucose-6-phosphatase (G-6-Pase) and membrane cholesterol to phospholipid ratios. In control fed rats given 6 i.p. injections of glucagon 350 micrograms/injection) at hourly intervals, percentage hepatic glycogen decreased nearly 30 fold, with liver homogenate G-6-Pase (U/mg protein) increasing 50% (p less than .02 relative to vehicle-injected controls) from .055 +/- .003 at 0h (n = 12) to .081 +/- .004 at 6h (n = 11). The increase in homogenate G-6-Pase was reflected in the isolated SER fraction by a 48% rise (p less than .01 relative to controls) in activity from a 0h value of .210 +/- .010 (n = 10) to a peak activity of .310 +/- .027 U/mg microsomal protein at 5 h (n = 12). G-6-Pase also increased in the rough endoplasmic reticulum (RER) reaching .242 +/- .023 U/mg protein at 4h (n = 14), but then declining to .209 +/- .019 U/mg protein at 6 h (n = 11). The changes in G-6-Pase were accompanied by alterations in the ratio of microsomal cholesterol to phospholipid, which decreased by 50% (p less than .002) in both RER and SER fractions signifying changes in membrane lipid environment. Ultrastructural analysis revealed a marked reduction in hepatic glycogen and conspicuous presence of elements of the SER in regions of the cytoplasm where glycogen was or presumably had been located.
D000818:Animals; D002784:Cholesterol / Q000032:analysis; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005934:Glucagon / Q000494:pharmacology*; D005952:Glucose-6-Phosphatase / Q000378:metabolism*; D007425:Intracellular Membranes / Q000032:analysis; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D008563:Membrane Lipids / Q000032:analysis; D008854:Microscopy, Electron; D008862:Microsomes, Liver / Q000201:enzymology*; D010743:Phospholipids / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D008112:Liver Glycogen; D008563:Membrane Lipids; D010743:Phospholipids; D005934:Glucagon; D002784:Cholesterol; D005952:Glucose-6-Phosphatase