ON THE FUNCTIONAL SIGNIFICANCE OF THE PANCREATIC β-CELL GLYCOGEN*

SUMMARY Glycogen was found to be a normal constituent of mammalian pancreatic β-cells. These stores of glycogen did not constitute metabolically inert deposits but were readily mobilized during ischemia. There was a close relationship between the content of glycogen and the glucose levels to which the β-cells were exposed. The islets from obese-hyperglycemic mice contained, for example, 10 mmoles of glucosyl residues (= 1.6 g glycogen) per kilogram dry weight, which is about 3 times as much as found in the lean littermates. A low glucose level was incompatible with the establishment of substantial glycogen stores. This might represent a relevant mechanism for protection against profound hypoglycemia by making the β-cells less sensitive to various stimulators of insulin release. The dibutyryl derivative of cyclic 3,5-AMP as well as compounds (glucagon and theophylline) known to increase the amount of this nucleotide in the pancreatic islets reduced the levels of glycogen when tested in an in vitro system with microdissected islets. On the other hand, epinephrine, which inhibits the synthesis of cyclic 3,5-AMP by stimulation of the α-adrenergic receptor sites, increased the islet glycogen level. There was a reduction of the glycogen content when the microdissected islets were exposed to glibenclamide, a potent hypoglycemic sulfonylurea compound. The sulfonylurea mobilization of glycogen might be explained in terms of a modified “phosphate potential” leading to increased amounts of AMP and inorganic phosphate at the expense of ATP.