Suppressed glucose metabolism in acinar cells might contribute to the development of exocrine pancreatic insufficiency in streptozotocin-induced diabetic mice.

High prevalence of exocrine pancreatic insufficiency has been observed in diabetic patients. However, the underlying mechanisms are not well known. Reduced cytosolic Ca(2+) signals in pancreatic acinar cells may contribute to lower digestive enzyme secretion. It is well known that adenosine triphosphate (ATP) regulates cytosolic Ca(2+) signals in acinar cells; however, little is known as to whether diabetes impairs glucose metabolism that produces ATP in acinar cells. Streptozotocin (STZ)-induced diabetic C57BL/6 mouse model was used. Four weeks after being diabetic, pancreatic acinar cells were isolated; and amylase secretion and contents, glucose utilization and oxidation, the activities of several key enzymes for glucose metabolism, and ATP and nicotinamide adenine dinucleotide phosphate (reduced form) (NADPH) contents were determined. Compared with controls, diabetic mice had lower body weight. Cholecystokinin-8- and acetylcholine-stimulated amylase secretion was significantly impaired, and total amylase activity in acinar cells of STZ-diabetic mice was markedly reduced. Glucose utilization and oxidation were suppressed; measured enzyme activities for glucose metabolism and the ATP and NADPH contents were significantly reduced. These data indicate that glucose metabolism and ATP and NADPH productions are very important for maintaining acinar cell normal function. Reduction of ATP (reduces cytosolic Ca(2+) signals) and NADPH (reduces cell capability for antioxidative stress) productions may contribute to the development of exocrine pancreatic insufficiency in STZ-diabetic mice.