Very low hepatic glycogen levels are achieved by overnight fasting of adrenalectomized (ADX) rats. Subsequent injection of dexamethasone (DEX), a synthetic glucocorticoid, stimulates marked increases in glycogen synthesis. Using this system and injecting 3H-galactose as a glycogen precursor 1 hr prior to sacrifice, the intralobular and intracellular patterns of labeled glycogen deposition were studied by light (LM) and electron (EM) microscopic radioautography. LM radioautography revealed that 1 hr after DEX treatment, labeling patterns for both periportal and centrilobular hepatocytes resembled those in rats with no DEX treatment: 18% of the hepatocytes were unlabeled, and 82% showed light labeling. Two hours after treatment with DEX, 14% of the hepatocytes remained unlabeled, and 78% were lightly labeled; however, 8% of the cells, located randomly throughout the lobule, were intensely labeled. An increased number of heavily labeled cells (26%) appeared 3 hr after DEX treatment; and by 5 hr 91% of the hepatocytes were intensely labeled. Label over the periportal cells at this time was aggregated, whereas centrilobular cells displayed dispersed label. EM radioautographs showed that 2 to 3 hr after DEX injection initial labeling of hepatocytes, regardless of their intralobular location, occurred over foci of smooth endoplasmic reticulum (SER) and small electron-dense particles of presumptive glycogen, and in areas of SER and distinct glycogen particles. After 5 hrs of treatment with DEX, the intracellular distribution of label reflected the glycogen patterns characteristic of periportal or centrilobular regions.

Hormonal control of hepatic glycogen and blood glucose levels is one of the major homeostatic mechanisms in mammals: glycogen is synthesized when portal glucose concentration is sufficiently elevated and degraded when glucose levels are low. We have studied initial events of hepatic glycogen synthesis by injecting the synthetic glucocorticoid dexamethasone (DEX) into adrenalectomized rats fasted overnight. Hepatic glycogen levels are very low in adrenalectomized rats, and DEX causes rapid deposition of the complex carbohydrate. Investigation of the process of glycogen deposition was performed by light and electron microscopic (EM) radioautography using [3H]galactose as a glycogen precursor. Rats injected with DEX for 2-3 h and [3H]galactose one hour before being killed displayed an increasing number of intensely labeled hepatocytes. EM radioautography revealed silver grains over small (+ 1 pm) ovoid or round areas of the cytosome that were rich in smooth endoplasmic reticulum (SER) and contained a high concentration of small dense particles. These distinct areas or foci of SER and presumptive glycogen (SERGE) were most numerous during initial periods of glycogen synthesis. After longer exposure to DEX (4-5 h) more typical deposits of cytoplasmic glycogen were evident in the SERGE regions. Several criteria indicated that the SERGE foci contained glycogen or presumptive glycogen: resemblance of the largest dense particles to/~-glycogen particles in EM; association of 3H-carbohydrate with the foci; removal of particles and label with a-amylase; and positive reaction with periodic acid-chromic acidsilver methenamine. The concentration of SER in the small foci and the association of newly formed glycogen particles with elements of SER suggest a role for this organelle in the initial synthesis of glycogen.Glycogen in hepatocytes represents an available reserve of glucose that is used to maintain appropriate blood glucose levels. The synthesis and breakdown of glycogen are precisely regulated by hormonal mechanisms and blood glucose levels (12,13,30). In general, glycogen synthesis occurs as the glucose levels in the portal vein increase and breakdown of the complex carbohydrate is stimulated by low blood glucose levels (12, 13).Although much information is available on the biochemistry of glycogen synthesis (l 2, 29) very little is known about the cellular and subcellular mechanisms in the synthesis of this important storage form of carbohydrate. More important, almost nothing is understood about the role of cellular organelles in the synthesis of glycogen. In this article we address these questions by studying a model system that allows description of the early morphological events in hepatic glycogen synthesis. Our data implicate the smooth endoplasmic reticulum (SER) ~ in this process.Patterns of glycogen deposition throughout the liver lobule are not necessarily uniform, but they are related in general to Abbreviations used in this paper. ADX, adrenalectomized; DEX, dexamethasone; EM and LM, electron and ...

The prevalence of gestational diabetes mellitus (GDM) is increasing because of the worldwide obesity/diabetes epidemic. The complications of untreated GDM affect both the mother and baby and include complications during pregnancy as well as increased risk of subsequent type-2 diabetes in mothers and offspring. Standard tests for hyperglycemia in diabetes, such as fasting glucose and hemoglobin (HbA1c), are currently not recommended for GDM screening. Instead, an oral glucose tolerance test is specified, which is invasive, time-consuming, and not easily accessible to many at-risk populations. In this study, we describe a multi-analyte maternal serum profile test that incorporates novel glycoprotein biomarkers and previously described GDM-associated markers. In screening for GDM by multi-analyte panel, the detection rate was 87% at a false-positive rate of 1%.