Glycogen accumulation in rat pancreatic islets: in vitro experiments

Area of Science:

• Biochemistry
• Endocrinology
• Medical Imaging

Background:

• Hyperglycemia leads to glycogen accumulation in pancreatic islets, but not acinar cells.
• This differential accumulation presents an opportunity for noninvasive imaging of the endocrine pancreas.

Purpose of the Study:

• To characterize the time course of glycogen accumulation in cultured pancreatic islets under high D-glucose conditions.
• To evaluate the use of D-[U-14C]glucose and 2-deoxy-2-[18F]fluoro-D-glucose for labeling islet glycogen.
• To investigate glycogenolysis and its impact on B-cell function.

Main Methods:

• Culturing pancreatic islets at 30 mM D-glucose with radiolabeled tracers (D-[U-14C]glucose or 2-deoxy-2-[18F]fluoro-D-glucose).
• Measuring 14C-labeled glycogen content over time.
• Inducing glycogenolysis by lowering D-glucose concentration and stimulating with forskolin and theophylline.
• Assessing 14CO2 generation and B-cell secretory response.
• Pre-treating islets with streptozotocin.

Main Results:

• Islet glycogen content increased with incubation time (150 min to 72 h) and was higher than in acinar cells.
• Accumulated glycogen remained stable for 60 min after removing the tracer.
• Glycogenolysis occurred at low glucose concentrations, enhanced by forskolin/theophylline, coinciding with 14CO2 release and altered B-cell secretion.
• 2-deoxy-2-[18F]fluoro-D-glucose resulted in higher radioactive glycogen content than D-[U-14C]glucose.
• Streptozotocin pre-treatment inhibited glycogen accumulation.

Conclusions:

• Glycogen accumulation in pancreatic islets under hyperglycemia is time-dependent and selective.
• Radiolabeled tracers, particularly 2-deoxy-2-[18F]fluoro-D-glucose, can effectively label islet glycogen.
• Understanding glycogen dynamics is crucial for developing imaging strategies for the endocrine pancreas.