Saleh Receives KO8 Clinical Investigator Award

Pitt Pediatrics congratulates Mohamed Saleh, MD, of the Division of Endocrinology, for receiving a KO8: Clinical Investigator Award from the NIH for his project Loss of the Exocrine Pancreas Improves Glucose Tolerance and Insulin Secretion. 

Type 2 diabetes (T2D) is a major health problem in the US and worldwide, causing high morbidity and mortality. There is also currently no cure for T2D. It is well known that a decrease in the first-phase insulin secretion is the earliest and most detrimental defect detected in impaired glucose tolerance (prediabetes) and T2D. Although studies have highlighted the existence of two intra- pancreatic axes of communication between the endocrine and exocrine pancreas (the insular–acinar axis and the acinar–insular axis), little attention has been paid to any direct effect of the exocrine pancreas on β-cell function. Saleh and team recently designed a surgical mouse model wherein a pancreatic ductal infusion of 1% acetic acid (AcA) led to complete ablation of the exocrine pancreas, but importantly with complete sparing of the islets. This model allowed them to study β-cell function in-situ in the pancreas, with the islets retaining their native innervation and vasculature, but in the absence of the exocrine pancreas.

They also established a genetic model that uses the diphtheria toxin receptor selectively expressed in acinar cells via the elastase promoter to quickly ablate acinar cells using diphtheria toxin. The preliminary data in mice, and now in non-human primates, show a significant improvement in glucose tolerance and first-phase insulin secretion to supranormal levels following exocrine pancreas ablation.