The Effect of Pancreatic Polypeptide on Glucose Disposal After Surgical Alterations of the Pancreas

Abstract

Surgical alterations of the pancreas result in anatomic changes that can affect postoperative glucose metabolism. Pancreas transplantation results in reduction of beta-cell mass, systemic release of insulin, and denervation. The authors hypothesized that such alterations affect peripheral glucose disposal to induce an "insensitivity" to endogenously (systemically) released insulin. Additionally, they hypothesized that surgically induced deficiency of the postprandial hormone, pancreatic polypeptide, might contribute to altered glucose disposal. The authors studied two surgical models in dogs known to be devoid of pancreatic polypeptide--70% proximal pancreatectomy (PPx) and PPx plus distal pancreas autotransplantation (PAT/B). Oral glucose challenge and euglycemic hyperinsulinemic clamp studies were performed before and after a 16-day "pulsed" infusion of pancreatic polypeptide. Both surgical procedures resulted in elevations in the integrated glucose response after oral glucose, which was not affected by pancreatic polypeptide infusion. Euglycemic clamp studies showed decreased hepatic glucose output (Ra) and overall glucose disposal (Rd) in the fasted state for both surgical groups. The transplant animals demonstrated significant decreases in Rd during the hyperinsulinemic challenge (3.2 +/- 0.01 versus 5.7 +/- 0.01 mg/kg/minute at 60 to 120 minutes for PAT/B versus control). After 16 days of pancreatic polypeptide infusion, however, basal Ra, as well as basal and 60- to 120-minute Rd values, were returned to control values in the transplant group. The authors conclude that pancreas transplantation results in altered glucose disposal, possibly due to an altered effectiveness of systemically released insulin. They conclude that pancreatic polypeptide is an important modulator of peripheral insulin action. Therefore, the role of pancreatic polypeptide must be taken into account when evaluating postoperative glucose metabolism in canine models of pancreas transplantation.

Pancreatic Polypeptide Administration Enhances Insulin Sensitivity and Reduces the Insulin Requirement of Patients on Insulin Pump Therapy

“…18 Isolated hepatic resistance to insulin, despite normal or increased peripheral insulin sensitivity, has also been shown in T3cDM due to CP, 19 pancreatic cancer, 20 pancreatic resection, 21 and cystic fibrosis, 22 and an increase in hepatocyte PP receptors, now referred to as Y4 receptors, 23 has been shown in CP. 24 Administration of PP has been shown to improve hepatic sensitivity to insulin and glucose homeostasis in rats, 10,25 dogs, 9,26,27 and patients 28,29 with T3cDM due to CP or pancreatic resection.…”