Pancreatic polypeptide administration improves abnormal glucose metabolism in patients with chronic pancreatitis.

Abstract

Chronic pancreatitis (CP) is associated with lowered plasma levels and a blunted nutrient-induced release of pancreatic polypeptide (PP). To investigate the possible role of PP on glucose metabolism, we studied male patients with documented CP (n = 5) and obesity-matched control subjects (NL) (n = 6). Hepatic glucose production (HGP) and overall glucose disposal rates were determined by [3-3H]glucose infusion during a hyperinsulinemic-euglycemic clamp during three separate admissions. Basal rates of HGP were higher in CP patients. In response to an infusion of insulin (60 pmol.m-2.min-1), HGP fell 91 +/- 5% in NL subjects but only 68 +/- 8% in CP subjects (P < 0.05). One month later, the clamp was repeated during the final 2 h of an 8-h infusion of bovine PP (2 pmol.kg-1.min-1). HGP before the insulin infusion and its subsequent suppression (NL: 83 +/- 5%; CP: 86 +/- 15%) were nearly identical between groups. In follow-up studies 1 month after the PP infusion, HGP both basally and in response to insulin alone were similar to the first study. During oral glucose tolerance tests (OGTT) performed 18 h after the PP infusion, subjects with normal (n = 7) baseline OGTT responses showed no effect. All patients with diabetic (n = 3) or nondiagnostic (n = 1) OGTT responses, however, demonstrated lowered mean plasma glucose levels (approximately -2.3 mmol/L; range: -0.6 to -7.2 mmol/L). OGTTs repeated 1 month after the PP treatment showed a return to pretreatment responses. We conclude that chronic pancreatitis accompanied by PP deficiency is associated with partial hepatic resistance both in the basal state and in response to hyperinsulinemia. This impairment is reversed after iv PP administration. PP deficiency may therefore play a role in the development of pancreatogenic diabetes caused by pancreatic injury.

“Blogs” and “Wikis” Are Valuable Software Tools for Communication Within Research Groups

“…When PP was infused along with insulin, suppression of hepatic glucose production significantly increased to about 65%. Using similar techniques to those employed in dogs, Brunicardi et al demonstrated similar findings in humans with chronic pancreatitis (18).…”

“…Obese subjects with abnormal oral glucose tolerance demonstrated elevated basal levels of PP and an exaggerated increase in PP levels in response to glucose stimulation. Brunicardi and Sun indicated that PP might play an important role in the regulation of glucose metabolism by affecting the hepatic response to insulin (3,18). Sun et al examined pancreatogenic diabetes in a canine model of chronic pancreatitis (3).…”

Diabetes of the exocrine pancreas

“…Notably, PP administration has been shown to improve glucose homeostasis and conservative surgical procedures that preserve the head of the pancreas appear to reduce the incidence of postoperative diabetes. 33 The release of incretin hormones may be disordered in DEP, leading to a suboptimal post-prandial insulin secretion. In normal physiology, fatty acids and other nutrients cause the release of glucagon-like peptide-1 (GLP-1) from intestinal L cells in the ileum and large intestine and glucose-dependent insulinotropic polypeptide from K cells of the small intestine.…”

Incidence, Demographics, and Clinical Characteristics of Diabetes of the Exocrine Pancreas (Type 3c): A Retrospective Cohort Study

“…This is caused by b-cell dysfunction following pancreatic inflammation or by absolute b-cell loss (5,6). In addition, pancreatic polypeptide upregulates insulin receptor expression in the liver, and its loss can lead to hepatic insulin resistance (7), an important physiological difference between diabetes of the exocrine pancreas and type 1 diabetes. Glucagon production from pancreatic a-cells is also diminished, which may explain the episodes of severe hypoglycemia that are reported in some patients (8,9).…”