Signaling Proteins Associated with Diabetic‐Induced Exocrine Pancreatic Insufficiency in Rats

Abstract

Diabetes mellitus (DM) is associated with pancreatic atrophy and compromised digestion of carbohydrates as a result of exocrine pancreatic insufficiency and lower alpha-amylase synthesis and secretion. The reduced production of digestive enzymes is likely to be caused by deregulated protein metabolism. The relative concentrations and phosphorylation of signaling proteins associated with protein translation, such as PKB, p70S6K1, 4E-BP1, ERK1/2, and also some of those implicated in protein breakdown, such as ubiquitin and NF-kappaB, in the pancreas of streptozotocin (STZ)-induced type I diabetic pancreas were measured using Western blotting. There were significant decreases in the levels of total PKB, p70S6K, 4E-BP1, ERK1/2, and NF-kappaB in the diabetic pancreas compared to control. In contrast, the phosphorylation of p70S6K1, 4E-BP1, ERK1/2, and protein ubiquitination increased significantly compared to controls. Together, these results indicate that STZ-induced DM leads to reduced levels of enzymes mediating protein synthesis while their phosphorylation is actually increased, perhaps in an attempt to maintain protein homeostasis, which is further compromised by heightened ubiquitin-dependent protein breakdown. It is likely that these factors are responsible for pancreatic atrophy, enzyme synthesis, and net protein loss in DM.

Activation of mTOR coincides with autophagy during ligation-induced atrophy in the rat submandibular gland

“…This is supported by the ABPAS staining where secretory glycoproteins (figure 1h) in the granules can still be seen in the periphery of the gland indicating these acinar cells may still be functional. Similar observations were made in a study of diabetes mellitus associated pancreatic atrophy, where, although a decrease in the production of digestive proteins was observed, there was an increase in phosphorylation of 4E-BP1 36.…”

Exocrine pancreatic insufficiency in type 1 and type 2 diabetes mellitus: do we need to treat it? A systematic review

“…Nowadays the role of signaling proteins in pancreatic inflammation and diabetes induced pancreatic insufficiency is getting more attention. In a previous study the levels of total PKB, p70S6K, 4 E-BP1, ERK1/2, and NF-kappaB in the diabetic pancreas compared to control were significant decreased, however, the phosphorylation of p70S6K1, 4 E-BP1, ERK1/2, and protein ubiquitination were increased significantly compared to control group [62]. Presumable, that these factors are liable for decreased enzyme synthesis and pancreatic atrophy.…”

Serum amylase and lipase levels in type 2 diabetes mellitus

“…Some authors suggested that, hyperglycemia can cause disturbance in cellular signaling that controls both transcription and protein metabolism in the pancreas leading to pancreatic exocrine insufficiency in DM 25 .…”